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1. Reaching the unreached through building trust: a mixed-method study on COVID-19 vaccination in rural Lao PDR

Author: Shogo Kubota, Sayaka Horiuchi, Ying-Ru Jacqueline Lo, Elizabeth M Elliott, Ketkesone Phrasisombath, Phonepaseuth Ounaphom, Laty Phimmachak, Ounkham Souksavanh, Pavina Vongsouvanh, Dimbintsoa Rakotomalala Robinson, Souliya Channavong, Eric Deharo, William Robert Everett Seal, and Bounfeng Phoummalaysith
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Introduction The global COVID-19 vaccine rollout has been impacted by socioeconomic disparities and vaccine hesitancy, but few studies examine reasons for changed attitudes. In Lao People’s Democratic Republic (Lao PDR), a nationwide government-led initiative was developed in response to COVID-19, focused on community health ownership and trust in primary healthcare. The intervention team including health and governance sectors conducted capacity-building workshops with local staff and community representatives and visited villages for vaccination outreach. This study investigates the impact of this intervention on COVID-19 vaccine acceptance in rural communities.Methods Conducted in Xiengkhuang province, Lao PDR, from December 2022 to February 2023, the study employed a sequential mixed-methods research design. Data on vaccinated individuals from 25 villages were collected from 11 primary healthcare units; pre-post analysis was applied. Qualitative data, gathered through interviews and focus group discussions with villagers, village authorities, health staff and local government (n=102) in six villages, underwent inductive thematic analysis.Results First-dose vaccine uptake after the intervention increased significantly (6.9 times). Qualitative analysis identified key reasons for vaccination hesitancy: (1) mistrust due to rumours and past experiences; (2) poor communication and inconsistent messaging and (3) challenges in access for priority groups. Influencing factors during the intervention included (1) effective local-context communication; (2) leveraging existing community structures and influential individuals in a multisectoral approach and (3) increased community motivation through improved satisfaction, ownership and relationships.Conclusion This study highlights the impact and methods of building trust with unreached populations in health interventions, emphasising locally led solutions. Successful reversal of vaccine hesitancy was achieved by addressing root causes and fostering ownership at community and local government levels through a ‘positive approach’. This diverges from conventional supplemental immunisation activities and holds potential for systematically building trust between unreached populations and health systems. Further research could explore the impacts of routine vaccination for sustained improvements in health equity.
Published: 2024
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2. Exposure assessment of 170 pesticide ingredients and derivative metabolites in people from the Central Andes of Peru

Author: Jorge Honles, Claire Clisson, Claudia Monge, Pedro Vásquez-Ocmín, Juan Pablo Cerapio, Sysay Palamy, Sandro Casavilca-Zambrano, Javier Herrera, Pascal Pineau, Eric Deharo, Vincent Peynet, and Stéphane Bertani
Subjects: Medicine, Science
Abstract: Abstract The Central Andes of Peru are a region of great concern regarding pesticide risk to the health of local communities. Therefore, we conducted an observational study to assess the level of pesticide contamination among Andean people. Analytical chemistry methods were used to measure the concentrations of 170 pesticide-related compounds in hair samples from 50 adult Andean subjects living in rural and urban areas. As part of the study, a questionnaire was administered to the subjects to collect information regarding factors that increase the risk of pesticide exposure. Our results indicate that Andean people are strongly exposed to agrochemicals, being contaminated with a wide array of pesticide-related compounds at high concentration levels. Multivariate analyses and geostatistical modeling identified sociodemographic factors associated with rurality and food origin that increase pesticide exposure risk. The present study represents the first comprehensive investigation of pesticide-related compounds detected in body samples collected from people living in the Central Andes of Peru. Our findings pinpoint an alarming environmental situation that threatens human health in the region and provide a rationale for improving public policies to protect local communities.
Published: 2022
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3. Cáncer de hígado: ¿Antigua o nueva amenaza para los jóvenes de países en vía de desarrollo?

Author: Juan Pablo Cerapio, Juan Contreras-Mancilla, Ramiro Fernández, Fournié Jean-Jacques, Eric Deharo, Stéphane Bertani, Pascal Pineau, Sandro Casavilca-Zambrano, and Eloy Ruiz
Subjects: cáncer de hígado, amenaza, jóvenes, países en vía de desarrollo, editorial, Medicine (General), R5-920
Abstract: Entre las neoplasias malignas más frecuentes del mundo, el carcinoma hepatocelular (CHC) es la segunda causa de muerte relacionada con el cáncer (1). Su incidencia se ha duplicado durante las dos últimas décadas y la mayor carga se produce en los países de ingresos bajos y medianos. Los tumores hepáticos primarios malignos suelen describirse como una patología que afecta principalmente a hombres mayores de 40 años con un hígado cirrótico; rara vez se han registrado en personas más jóvenes y normalmente, en menores de 40, lo más común es el hepatoblastoma.
Published: 2022
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4. Zootherapeutic uses of animals excreta: the case of elephant dung and urine use in Sayaboury province, Laos

Author: Jean-Marc Dubost, Phommachack Kongchack, Eric Deharo, Palamy Sysay, Chithdavone Her, Lamxay Vichith, Duffillot Sébastien, and Sabrina Krief
Subjects: Zootherapy, Elephas maximus, Asian elephant, Lao PDR, Feces, Faeces, Other systems of medicine, RZ201-999, Botany, QK1-989
Abstract: Abstract Background Despite a widespread aversion towards faeces and urine, animal excreta are used in traditional medicine in many countries since centuries, but records are scattered and few therapeutic uses have been accurately documented while in the current context of emerging zoonoses such records may be of major interest. Methodology In this study, we investigated the therapeutic uses that mahouts in Xayaboury province, Lao PDR make of elephant urine and faeces as well as of the brood chamber that beetles (Heliocopris dominus) fashion from elephant dung. Semi-structured interviews were conducted with mahouts on elephant diet, health problems and responses to disease, andwhether they use elephant products. Data were supplemented by interviews with traditional healers. Results Seven respondents reported the use of elephant urine in ethnoveterinary care for elephants and in human medicine in case of diabetes and otitis. 25 respondents reported therapeutic use of elephant faeces (EF) and elephant dung beetle brood chambers. The major indications are gastrointestinal and skin problems. Macerations or decoctions are drunk or used externally as a lotion. The mahouts attribute the therapeutic effectiveness of EFs to their content which includes the remains of many species from the elephant diet which they consider to be medicinal. Discussion The indications of these uses are consistent with pharmacological and clinical studies highlighting the properties of different animals’ urine and faeces and their curative potential tested in vivo. The acknowledgement by the mahouts of medicinal properties of elephant faecal bolus contrasts with the rare justifications of animal material use recorded in zootherapeutic studies, which falls within the symbolic domain. However, numerous studies highlight the preponderant role of the microbiota in physiological processes, raising the hypothesis of a curative action of EF, by rebalancing the user’s microbiota. Conclusion The therapeutic uses of EF preparations despite their possible curative properties are a potential source of zoonotic transmission from elephants to humans. In the current context of globalisation of trade which favours the emergence of zoonoses and in relation with the issue of One Health, it becomes crucial to further document the zootherapeutic practices to prevent emerging diseases. As elephants and local related ethnoethological knowledge are threatened, documenting them is urgent to contribute to their preservation.
Published: 2021
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5. Savoirs médicinaux interspécifiques et interactions entre cornacs et éléphants dans le district de Thongmyxay au Laos

Author: Jean-Marc Dubost, Eric Deharo, Sysay Palamy, Chithdavone Her, Chiobouaphong Haekovilay, Lamxay Vichith, Sébastien Duffilot, and Sabrina Krief
Subjects: multispecies cultures, interspecific knowledge, elephants, ethnoveterinary medicine, traditional medicine, Anthropology, GN1-890
Abstract: The mahouts and the elephants of Thongmyxay district in Laos form an original hybrid community composed of humans and an animal species represented by both wild and domestic animals (elephants). We investigated in particular the interactions between mahouts' observation of elephants and their own medicinal practices (human and ethnoveterinary), which have been the subject of two previous publications. Based on this material, supplemented by data collected on the status of domestic village elephants and interviews with four local healers, we discuss here with a multispecies approach combining ethnographic data and ethological knowledge, the modalities of construction and possible exchanges of medicinal knowledge between the two species. Elephants have a status characterised by a double hybridity: wild and domestic on the one hand (with ontological circulations from one state to the other), and animal and human on the other. The part of humanity attributed to the elephants is reflected in particular in the self-agency that is recognised in their ability to heal themselves when they are suffering, which leads to the therapeutic use of their dung by Mahouts. The mahouts include in their ethnoveterinary care of the elephants plants that they see the elephants use when they are ill. The medicinal uses they make of some of these plants in their households are more consistent with their observations of these elephant behaviours than it is with the use of the same items by local healers, suggesting a transfer of medicinal knowledge from elephants to mahouts.Since some of the village elephants in Thongmyxay are still periodically released and come into contact with their wild counterparts, the domestication space forms an interface between humans, wild elephants and the forest, and we discuss conversely the possibility of knowledge transfer from mahouts to village elephants through the ethnoveterinary care they receive.This knowledge which is precious for the health and well-being of people and elephants in Laos is threatened by the reduction of the forest cover sheltering the resources used, and by the relocation of village elephants to tourist centres. Thus, emerges the need to think the conservation of the intangible heritage represented by the knowledge of hybrid communities in terms of interspecific heritage, implying that along with the preservation of the ecosystems that host the resources involved in this knowledge, care must be taken to maintain their access to all the populations (human and animal) that use them.
Published: 2022
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6. Interspecific medicinal knowledge and Mahout-Elephant interactions in Thongmyxay district, Laos

Author: Jean-Marc Dubost, Eric Deharo, Sysay Palamy, Chithdavone Her, Chiobouaphong Phaekovilay, Lamxay Vichith, Sébastien Duffillot, and Sabrina Krief
Subjects: multispecies cultures, interspecific knowledge, elephants, ethnoveterinary medicine, traditional medicine, Anthropology, GN1-890
Abstract: The mahouts and the elephants of Thongmyxay district in Laos form an original hybrid community composed of humans and an animal species represented by both wild and domestic animals (elephants). We investigated in particular the interactions between mahouts' observation of elephants and their own medicinal practices (human and ethnoveterinary), which have been the subject of two previous publications. Based on this material, supplemented by data collected on the status of domestic village elephants and interviews with four local healers, we discuss here with a multispecies approach combining ethnographic data and ethological knowledge, the modalities of construction and possible exchanges of medicinal knowledge between the two species.Elephants have a status characterised by a double hybridity: wild and domestic on the one hand (with ontological circulations from one state to the other), and animal and human on the other. The part of humanity attributed to the elephants is reflected in particular in the self-agency that is recognised in their ability to heal themselves when they are suffering, which leads to the therapeutic use of their dung by Mahouts. The mahouts include in their ethnoveterinary care of the elephants plants that they see the elephants use when they are ill. The medicinal uses they make of some of these plants in their households are more consistent with their observations of these elephant behaviours than it is with the use of the same items by local healers, suggesting a transfer of medicinal knowledge from elephants to mahouts.Since some of the village elephants in Thongmyxay are still periodically released and come into contact with their wild counterparts, the domestication space forms an interface between humans, wild elephants and the forest, and we discuss conversely the possibility of knowledge transfer from mahouts to village elephants through the ethnoveterinary care they receive.This knowledge which is precious for the health and well-being of people and elephants in Laos is threatened by the reduction of the forest cover sheltering the resources used, and by the relocation of village elephants to tourist centres. Thus, emerges the need to think the conservation of the intangible heritage represented by the knowledge of hybrid communities in terms of interspecific heritage, implying that along with the preservation of the ecosystems that host the resources involved in this knowledge, care must be taken to maintain their access to all the populations (human and animal) that use them.
Published: 2022
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7. Estimating the burden of hepatitis B virus infection in Laos between 2020 and 2021: A cross-sectional seroprevalence survey

Author: Philavanh Sitbounlang, Eric Deharo, Vatthanaphone Latthaphasavang, Agnès Marchio, Chanthala Soukhsakhone, Vonephet Soinxay, Mayfong Mayxay, Nicolas Steenkeste, Pascal Vincelot, Stéphane Bertani, Sysay Palamy, Phimpha Paboriboune, and Pascal Pineau
Subjects: Hepatitis B virus, Southeast Asia, Laos, Endemic country, Universal Immunization, Medicine (General), R5-920
Abstract: Summary: Background: Laos is considered highly endemic for persistent infection with hepatitis B virus (HBV). To eliminate this burden, it has gradually implemented universal anti-hepatitis B immunisation of newborns over the past two decades. Methods: Using VIKIA® HBsAg, a rapid test for the qualitative detection of the HBV surface antigen, we conducted between Sep 1st, 2020 and Aug 31st, 2021 the largest prospective prevalence survey ever in Laos. This survey included blood donors (BD, n = 42,277), patients attending care in capital and provincial hospitals (n = 37,347) including attending mothers (n = 20,548), HIV-infected patients (n = 7439, recruited from 2009 to 2020), students from the Health Sciences University (n = 609), and outpatients (n = 350) coming for diagnosis at the Center Infectiology Lao-Christophe Mérieux in Vientiane. In total, 88,022 persons were tested, representing approximately 1.22% of the national population. To reach a reasonable estimate of HBsAg prevalence in Laos, we segmented the population according to three variables, age (≤20 years as a cut-off), sex, and geographical origin. BD values were used to estimate HBsAg prevalence in patients aged
Published: 2022
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8. Concealed for a Long Time on the Marches of Empires: Hepatitis B Virus Genotype I

Author: Agnès Marchio, Philavanh Sitbounlang, Eric Deharo, Phimpha Paboriboune, and Pascal Pineau
Subjects: Hepadnaviridae, HBV, genotype I, recombinant, ethnic minorities, Southeast Asian Massif, Biology (General), QH301-705.5
Abstract: Genotype I, the penultimate HBV genotype to date, was granted the status of a bona fide genotype only in the XXIst century after some hesitations. The reason for these hesitations was that genotype I is a complex recombinant virus formed with segments from three original genotypes, A, C, and G. It was estimated that genotype I is responsible for only an infinitesimal fraction (2 spreading from Eastern India to China, inhabited by a little more than 100 million persons belonging primarily to ethnic minorities speaking various types of languages (Tibeto-Burman, Austroasiatic, and Tai-Kadai) who managed to escape the authority of central states during historical times. Genotype I consists of two subtypes: I1, present in China, Laos, Thailand, and Vietnam; and I2, encountered in India, Laos, and Vietnam.
Published: 2023
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9. Comparison of the antimalarial activity of a Colombian traditional Uitoto remedy with laboratory preparations

Author: Zully Johana Rodriguez, Yinneth Victoria Rodríguez, José Octavio García, María Helena Arias, Eric Deharo, and Giovanny Garavito
Subjects: antimalarials, curarea toxicofera, ethnopharmacology, traditional medicine, improved traditional medicine, Infectious and parasitic diseases, RC109-216
Abstract: Background & objectives: In Colombian Amazonia, Uitoto indigenous people use a preparation of Curarea toxicofera (Menispermaceae) to prevent and treat malaria. To open the way for the production of a standardized herbal remedy, we compared the activity of the traditional preparation with laboratory preparations. Methods: People were interviewed on their mode of use and preparation of what is considered the best remedy against fevers in this area. The herbal remedy was prepared according to the healer’s recommendations. The plant was also submitted to continuous distillation and percolation extraction. The preparations were then tested against Plasmodium falciparum, in vitro. Traditional preparation and extract obtained by percolation were tested on Plasmodium berghei infected mice. Chemical profiles were also explored by thin-layer chromatography. Results: Yields of extraction were around 7% in the preparations (percolation was the most efficient). The phytochemical profile showed a mix of steroids, flavonoids and alkaloids qualitatively similar in all preparations. In vitro, the extracts showed inhibitory concentration 50
Published: 2020
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10. Hmong herbal medicine and herbalists in Lao PDR: pharmacopeia and knowledge transmission

Author: Jean Marc Dubost, Chiobouaphong Phakeovilay, Chithdavone Her, Audrey Bochaton, Elizabeth Elliott, Eric Deharo, Mouachan Xayvue, Somsanith Bouamanivong, and Geneviève Bourdy
Subjects: Hmong, Medicinal plant, Lao PDR, Pharmacopeia, Traditional medicine, TEK, Other systems of medicine, RZ201-999, Botany, QK1-989
Abstract: Abstract Background In Lao PDR, the Hmong ethnic group has extensive knowledge about the use of medicinal plants. However, despite the importance of the Hmong pharmacopeia as a primary health care resource, no study has been undertaken to thoroughly document medicinal plant knowledge and its transmission. Objectives of this study are (i) to describe and characterize Hmong pharmacopeia, and (ii) to understand how medicinal plant knowledge is transmitted and spread among Hmong in Lao PDR, in order to assess whether this knowledge base is under threat. Methods In order to describe Hmong pharmacopeia, a total of 14 interlocutors were interviewed in three provinces (Bokeo, Xieng Khouang, and Vientiane), using “walk in the wood” methodology. To gain insight about knowledge transmission, semi-structured interviews were conducted with 28 people. Twenty of them were herbalists. Data analysis was performed using univariate analysis for the description of the pharmacopeia. Medicinal plant knowledge consistency was assessed through use and plant name overlapping. Answers to the semi-structured interview on knowledge transmission were analyzed qualitatively. Results Three hundred thirty-three different medicinal species were collected. The majority of uses attributed to plants were gastrointestinal conditions (22% of total use reports), gynecological conditions and sexually transmitted disease (12%), skin affections (8%), kidney and bladder problems (5%), physical traumas (5%), and aphrodisiac (or male tonics; 5%). Use convergences are more marked in the gynecological sphere, but there is a strong heterogeneity in practices and knowledge. Medicinal plant knowledge transmission is oral, gained from direct experience since childhood, matrilineal, and kept strictly within the family lineage. Apparent limited consensus on uses might stem from the method of knowledge transmission and to the economic value given to medicinal plants. Discussion Use pattern of species from the Hmong pharmacopeia does not appear to be strikingly different from the national Lao pharmacopeia. Differences may lie in the methods and reasons for knowledge transmission. It can be proposed that the economic value given to plants helps in keeping the knowledge alive, and encourages its transmission. Conclusion Hmong traditional medicine is constantly evolving in a dynamic process and aims to respond to health problems faced by the local population. Herbalists appear as health fully fledged actors and should be recognized and valued as such.
Published: 2019
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11. Dengue virus reduces AGPAT1 expression to alter phospholipids and enhance infection in Aedes aegypti.

Author: Thomas Vial, Wei-Lian Tan, Benjamin Wong Wei Xiang, Dorothée Missé, Eric Deharo, Guillaume Marti, and Julien Pompon
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: More than half of the world population is at risk of dengue virus (DENV) infection because of the global distribution of its mosquito vectors. DENV is an envelope virus that relies on host lipid membranes for its life-cycle. Here, we characterized how DENV hijacks the mosquito lipidome to identify targets for novel transmission-blocking interventions. To describe metabolic changes throughout the mosquito DENV cycle, we deployed a Liquid chromatography-high resolution mass spectrometry (LC-HRMS) workflow including spectral similarity annotation in cells, midguts and whole mosquitoes at different times post infection. We revealed a major aminophospholipid reconfiguration with an overall early increase, followed by a reduction later in the cycle. We phylogenetically characterized acylglycerolphosphate acyltransferase (AGPAT) enzyme isoforms to identify those that catalyze a rate-limiting step in phospholipid biogenesis, the acylation of lysophosphatidate to phosphatidate. We showed that DENV infection decreased AGPAT1, but did not alter AGPAT2 expression in cells, midguts and mosquitoes. Depletion of either AGPAT1 or AGPAT2 increased aminophospholipids and partially recapitulated DENV-induced reconfiguration before infection in vitro. However, only AGPAT1 depletion promoted infection by maintaining high aminophospholipid concentrations. In mosquitoes, AGPAT1 depletion also partially recapitulated DENV-induced aminophospholipid increase before infection and enhanced infection by maintaining high aminophospholipid concentrations. These results indicate that DENV inhibition of AGPAT1 expression promotes infection by increasing aminophospholipids, as observed in the mosquito's early DENV cycle. Furthermore, in AGPAT1-depleted mosquitoes, we showed that enhanced infection was associated with increased consumption/redirection of aminophospholipids. Our study suggests that DENV regulates aminophospholipids, especially phosphatidylcholine and phosphatidylethanolamine, by inhibiting AGPAT1 expression to increase aminophospholipid availability for virus multiplication.
Published: 2019
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12. Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration

Author: Miguel Quiliano, Adela Mendoza, Kim Y. Fong, Adriana Pabón, Nathan E. Goldfarb, Isabelle Fabing, Ariane Vettorazzi, Adela López de Cerain, Ben M. Dunn, Giovanny Garavito, David W. Wright, Eric Deharo, Silvia Pérez-Silanes, Ignacio Aldana, and Silvia Galiano
Subjects: Antimalarial, Antiplasmodial, Arylamino alcohol, Plasmepsin II enzyme, Hemozoin inhibition, Mannich reaction, Infectious and parasitic diseases, RC109-216
Abstract: Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 ≤ 0.19 μM) and multidrug resistant (FCR-3 IC50 ≤ 0.40 μM and C235 IC50 ≤ 0.28 μM) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed. Notably, compound 22 displays excellent parasitemia reduction (98 ± 1%), and complete cure with all treated mice surviving through the entire period with no signs of toxicity. One important factor is the agreement between in vitro potency and in vivo studies. Target exploration was performed; this chemotype series exhibits an alternative antimalarial mechanism.
Published: 2016
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13. Herbal Medicine Practices of Patients With Liver Cancer in Peru: A Comprehensive Study Toward Integrative Cancer Management

Author: Teresa Rojas Rojas MSPH, Geneviève Bourdy PharmD, PhD, Eloy Ruiz MD, Juan-Pablo Cerapio MSc, Pascal Pineau PhD, Jacques Gardon MD, PhD, Franco Doimi MD, Xavier Deparis MD, PhD, Eric Deharo PharmD, PhD, and Stéphane Bertani PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Rationale: The highest burden of liver cancer occurs in developing countries, where the use of herbal medicine (HM) is still widespread. Despite this trend, few studies have been conducted to report HM practices of patients with a hepatic tumor in the developing world. Hence, this study aimed to document the use of HM among patients with liver cancer in Peru. Study Design and Methods: A comparative behavioral epidemiological survey was conducted among liver cancer patients attending the National Cancer Institute of Peru. Information was obtained by direct interviews based on a semistructured questionnaire. The use of HM in Peruvian liver cancer patients was reported, first, regarding general consumption prior to the onset of disease, and second, after the appearance of symptoms that patients would relate to their tumor. In parallel, general consumption of HM in noncancerous people was assessed as a comparative figure. A correspondence analysis was performed to reveal potential associations between the symptoms of cancer and the specific use of HM. Results: Eighty-eight patients and 117 noncancerous individuals participated in the survey. Overall, 68.3% of the people interviewed claimed to use HM on a regular basis for general health preservation. Furthermore, 56.8% of the patients turned to plants first to treat the disorders for which they later came to the cancer care center. When compared with the number of plant species used routinely (n = 78), a selection of plants was made by patients in response to the symptoms of cancer (n = 46). At least 2 plant species, Aloe vera and Morinda citrifolia , were significantly associated with the treatment of liver cancer–related symptoms in the patient group. Conclusions: The present study is the first survey on the HM practices of patients with liver cancer in Latin America and, more broadly, in the developing world. Our findings confirm that HM remains one of the principal primary health care resources in Peru, even for a severe disease like liver cancer. These traditional, complementary and alternative medicine practices should be taken into consideration in Peruvian health programs aiming to educate the population in cancer prevention and treatment, as well as integrative cancer management.
Published: 2018
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14. A Seven-Year Retrospective Study on the Surveillance of Hepatitis B in Laos

Author: Phimpha Paboriboune, Thomas Vial, François Chassagne, Philavanh Sitbounlang, Sengaloun Soundala, Stéphane Bertani, Davone Sengmanothong, Francois-Xavier Babin, Nicolas Steenkeste, Paul Dény, Pascal Pineau, and Eric Deharo
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Objective. Lao PDR is one of the most highly endemic countries for hepatitis B in Asia and the second country for liver cancer incidence. Therefore, the follow-up of infected individuals through predictive serological markers is of utmost importance to monitor the progression of the pathology and take the decision on treatment. Methods. A retrospective-descriptive cohort study was conducted on 3,857 HBV-infected patients. Information about infection status (viral load, VL), liver function (aminotransferases), and treatments was recorded. Results. M/F sex ratio was 1.77 for a median age of 37. Patients under 37 displayed higher VL than older ones and men had higher VL than women. Initial VL ranged from 2,000 U/L. Men had higher aminotransferase than women. Globally 20% of patients received treatment (mainly immunostimulant and reverse-transcriptase inhibitors); 11% had high levels of VL and liver enzymes, but only 2% of them were treated. Conclusion. Public health decisions should be taken urgently to rationalise vaccination and provide fair access to early diagnosis and treatment; otherwise the burden of HBV-associated diseases will be overwhelming for Laos in the near future.
Published: 2018
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15. Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

Author: Emeline Houël, German Gonzalez, Jean-Marie Bessière, Guillaume Odonne, Véronique Eparvier, Eric Deharo, and Didier Stien
Subjects: therapeutic switching, antifungal agents, antiparasitic agents, Leishmania, peritoneal macrophages, sesquiterpenes, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract: This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.
Published: 2015
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16. Synthesis, Biological Evaluation and Structure-Activity Relationships of New Quinoxaline Derivatives as Anti-Plasmodium falciparum Agents

Author: Ana Gil, Adriana Pabón, Silvia Galiano, Asunción Burguete, Silvia Pérez-Silanes, Eric Deharo, Antonio Monge, and Ignacio Aldana
Subjects: Plasmodium falciparum, antimalarial agents, quinoxaline, quinoxaline 1,4-di-N-oxide, chalcone, Organic chemistry, QD241-441
Abstract: We report the synthesis and antimalarial activities of eighteen quinoxaline and quinoxaline 1,4-di-N-oxide derivatives, eight of which are completely novel. Compounds 1a and 2a were the most active against Plasmodium falciparum strains. Structure-activity relationships demonstrated the importance of an enone moiety linked to the quinoxaline ring.
Published: 2014
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17. New Amide Derivatives of Quinoxaline 1,4-di-N-Oxide with Leishmanicidal and Antiplasmodial Activities

Author: Eric Deharo, German Gonzalez, Antonio Monge, Silvia Pérez-Silanes, Silvia Galiano, Carlos Barea, Adriana Pabón, and Ignacio Aldana
Subjects: quinoxaline, 1,4-di-N-oxide, leishmanicidal, antiplasmodial, Organic chemistry, QD241-441
Abstract: Malaria and leishmaniasis are two of the World’s most important tropical parasitic diseases. Continuing with our efforts to identify new compounds active against malaria and leishmaniasis, twelve new 1,4-di-N-oxide quinoxaline derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum FCR-3 strain, Leishmania infantum and Leishmania amazonensis. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. The results obtained indicate that a cyclopentyl derivative had the best antiplasmodial activity (2.9 µM), while a cyclohexyl derivative (2.5 µM) showed the best activity against L. amazonensis, and a 3-chloropropyl derivative (0.7 µM) showed the best results against L. infantum. All these compounds also have a Cl substituent in the R7 position.
Published: 2013
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18. Hepatocellular carcinoma surgery outcomes in the developing world: A 20-year retrospective cohort study at the National Cancer Institute of Peru

Author: Eloy Ruiz, Teresa Rojas Rojas, Francisco Berrospi, Ivan Chávez, Carlos Luque, Luis Cano, Franco Doimi, Pascal Pineau, Eric Deharo, and Stéphane Bertani
Subjects: Health sciences, Pathobiology of cancer, Cancer, Treatment of cancer, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: In the developing world, most patients with hepatocellular carcinoma present with advanced-stage disease, considered to be incurable based on current therapeutic algorithms. Here, we demonstrate that curative liver resection is achievable in a portion of Peruvian patients not addressed by these treatment algorithms. We conducted a retrospective cohort study of 253 hepatocellular carcinoma patients that underwent a curative hepatectomy between 1991 and 2011 at the National Cancer Institute of Peru. The median age of the cohort was 36 years, and merely 15.4% of the patients displayed cirrhosis. The average tumor size was over 14 cm in diameter, resulting in 76.3% of major hepatectomies performed. The 5- and 10-year survival probability estimates were 37.5% and 26.2%, respectively. Age (>44 vs. ≤44 years old; P = 0.005), tumor size (>10 cm vs. ≤10 cm in diameter; P = 0.009), cirrhosis (P < 0.001), satellite lesions (P < 0.001), macroscopic vascular invasion (P < 0.001), allogeneic blood transfusion (P = 0.011), and spontaneous rupture of the tumor (P = 0.006) were independent predictive factors for prognosis. Hepatocellular carcinomas in Peru are characterized by a distinct clinical presentation with notable features compared with those typically described throughout relevant literature. Despite a large number of advanced-stage hepatocellular carcinomas, the outcomes of liver resection observed in the present study were in good standing with the results previously described in other series. It thus appears that staging systems and associated therapeutic algorithms designed for use in the developed world remain inadequate in certain populations, especially in the context of Peruvian patients. Our findings suggest that clinicians in the developing world should reconsider management guidelines pertaining to hepatocellular carcinoma. Indeed, we hypothesize that, in developing countries, a strict adherence to these therapeutic algorithms might create a selection bias resulting in the dismissal of patients who could eventually be treated.
Published: 2016
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19. The in vivo antimalarial activity of methylene blue combined with pyrimethamine, chloroquine and quinine

Author: Giovanny Garavito, Stéphane Bertani, Miguel Quiliano, Alexis Valentin, Ignacio Aldana, and Eric Deharo
Subjects: antimalarials, methylene blue, drug combination, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract: The effectiveness of methylene blue (MB) combined with pyrimethamine (PYR), chloroquine (CQ) or quinine (Q) was examined in a classical four-day suppressive test against a causative agent of rodent malaria, Plasmodium berghei. A marked potentiation was observed when MB was administered at a non-curative dose of 15 mg/kg/day in combination with PYR (0.19 mg/kg/day) or Q (25 mg/kg/day). No synergy was found between MB (15 mg/Kg) and CQ (0.75 mg/Kg). Our results suggest that the combination of MB with PYR or Q may improve the efficacy of these currently used antimalarial drugs.
Published: 2012
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20. Antiplasmodial and Leishmanicidal Activities of 2-Cyano-3-(4-phenylpiperazine-1-carboxamido) Quinoxaline 1,4-Dioxide Derivatives

Author: Carlos Barea, Adriana Pabón, Silvia Galiano, Silvia Pérez-Silanes, German Gonzalez, Chloe Deyssard, Antonio Monge, Eric Deharo, and Ignacio Aldana
Subjects: quinoxaline, piperazine, Plasmodium, Leishmania, VERO, Organic chemistry, QD241-441
Abstract: Malaria and leishmaniasis are two of the World’s most important tropical parasitic diseases. Thirteen new 2-cyano-3-(4-phenylpiperazine-1-carboxamido) quinoxaline 1,4-dioxide derivatives (CPCQs) were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against erythrocytic forms of Plasmodium falciparum and axenic forms of Leishmania infantum. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. None of the tested compounds was efficient against Plasmodium, but two of them showed good activity against Leishmania. Toxicity on VERO was correlated with leishmanicidal properties.
Published: 2012
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21. COMPLEMENTARY FINDINGS ON THE ANTIMALARIAL ACTIVITY AND TOXICITY OF METHYLENE BLUE HALLAZGOS COMPLEMENTARIOS SOBRE LA ACTIVIDAD ANTIMALÁRICA DEL AZUL DE METILENO Y SU TOXICIDAD

Author: Giovanny GARAVITO, Stephane BERTANI, and Eric DEHARO
Subjects: Antipalúdicos, Plasmodium, Malaria, Azul de metileno, Antimalarials, Methylene blue, Food processing and manufacture, TP368-456, Pharmaceutical industry, HD9665-9675
Abstract: Methilene blue was reported as the first synthetic antimalarial by Ehrlich in 1881. It is currently no longer used for that purpose but it should be reconsidered since new economic alternatives are urgently needed in the arsenal of antimalarial drugs. The antimalarial activity of methylene blue is investigated here in vivo against rodent malaria parasites. 15 mg/kg daily dose of methylene blue inhibits 50% of the erythrocytic parasite growth of Plasmodium berghei and P. yoelii nigeriensis, while on hepatic stages of P. yoelii yoelii is almost inactive. In cell culture experiments with the lymphoblast-like BJAB cells line, it is 20 times more cytotoxic than chloroquine. Nevertheless, methylene blue shows a similar selectivity index as chloroquine against strains of different level of sensitivity of P. falciparum original from different geographical areas.En 1881, Ehrlich reportó el azul de metileno como el primer antimalárico sintético, pero dejo de ser empleado con este propósito; el debe ser reconsiderado pues son necesarias con urgencia nuevas alternativas de bajo costo, en el arsenal de medicamentos antimaláricos. En este trabajo la actividad antimalárica del azul de metileno es evaluada in vivo frente a parásitos de malaria murina. Una dosis de 15 mg/kg/día inhibe el 50% del crecimiento eritrocítico parasitario de Plasmodium berghei y P. yoelii nigeriensis, en tanto que es prácticamente inactivo frente a los estadios hepáticos de P. yoelii yoelii. Sobre un cultivo de la línea celular linfoblástica BJAB, el azul de metileno es 20 veces más citotóxico que la cloroquina, no obstante el azul de metileno presenta valores de índice de selectividad del mismo nivel que la cloroquina, frente a varias cepas de P. falciparum de diferentes niveles de sensibilidad y provenientes de diferentes lugares geográficos.
Published: 2008

22. A peculiar mutation spectrum emerging from young peruvian patients with hepatocellular carcinoma.

Author: Agnès Marchio, Stéphane Bertani, Teresa Rojas Rojas, Franco Doimi, Benoît Terris, Eric Deharo, Anne Dejean, Eloy Ruiz, and Pascal Pineau
Subjects: Medicine, Science
Abstract: Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms.
Published: 2014
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23. Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives

Author: Asunción Burguete, Yannick Estevez, Denis Castillo, Germán González, Raquel Villar, Beatriz Solano, Esther Vicente, Silvia Pérez Silanes, Ignacio Aldana, Antonio Monge, Michel Sauvain, and Eric Deharo
Subjects: quinoxaline, anti-leishmanial, structure-activity, Leishmaniasis, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract: A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl)-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.
Published: 2008
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24. An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations.

Author: Stéphane Bertani, Pascal Pineau, Sebastian Loli, Julien Moura, Mirko Zimic, Eric Deharo, and Eloy Ruiz
Subjects: Medicine, Science
Abstract: BackgroundIn South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country.MethodsA retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin.ResultsSurprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics.ConclusionsThe analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.
Published: 2013
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25. COMPLEMENTARY FINDINGS ON THE ANTIMALARIAL ACTIVITY AND TOXICITY OF METHYLENE BLUE.

Author: Giovanny GARAVITO, Stephane BERTANI, and Eric DEHARO
Subjects: Antimalarials, Plasmodium, Malaria, Methylene blue., Food processing and manufacture, TP368-456, Pharmaceutical industry, HD9665-9675
Abstract: Methilene blue was reported as the first synthetic antimalarial by Ehrlich in 1881. It is currently no longer used for that purpose but it should be reconsidered since new economic alternatives are urgently needed in the arsenal of antimalarial drugs. The antimalarial activity of methylene blue is investigated here in vivo against rodent malaria parasites. 15 mg/kg daily dose of methylene blue inhibits 50% of the erythrocytic parasite growth of Plasmodium berghei and P. yoelii nigeriensis, while on hepatic stages of P. yoelii yoelii is almost inactive. In cell culture experiments with the lymphoblast-like BJAB cells line, it is 20 times more cytotoxic than chloroquine. Nevertheless, methylene blue shows a similar selectivity index as chloroquine against strains of different level of sensitivity of P. falciparum original from different geographical areas.
Published: 2009

26. Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2, 1-f][1, 2, 4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2, 3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors.

Author: Julio Caballero, Miguel Quiliano, Jans H. Alzate-Morales, Mirko Zimic, and Eric Deharo
Published: 2011
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27. Liver cancer: a new old threat for young people in developing countries?

Author: Juan Pablo Cerapio, Juan Contreras-Mancilla, Ramiro Fernández, Fournié Jean-Jacques, Eric Deharo, Stéphane Bertani, Pascal Pineau, Sandro Casavilca-Zambrano, Eloy Ruiz, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), TOUCAN Laboratoire d'Excellence Toulouse Cancer, Laboratoire Mixte International d'Oncologie Anthropologique Moléculaire = International Joint Laboratory of Molecular Anthropological Oncology (LOAM), Institut de Recherche pour le Développement (IRD [Pérou]), Universidad Peruana Cayetano Heredia (UPCH), Instituto Nacional de Enfermedades Neoplasicas [Lima, Pérou] (INEN), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Universidad de Huánuco [Huánuco, Pérou], Esta publicación fue apoyada por el programa de Laboratorios Mixtos Internacionales (LMI) del Instituto francés de Investigación para el Desarrollo (IRD) y por las acciones Marie Skłodowska-Curie (MSCA) del programa H2020 de la Unión Europea, bajo convenio de subvención N° 823935., European Project: 823935,H2020-MSCA-RISE-2018,COCLICAN(2018), Bertani, Stéphane, and Collaborative Consortium for the early detection of Liver Cancer - COCLICAN - - H2020-MSCA-RISE-20182018-11-01 - 2022-10-31 - 823935 - VALID
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, editorial, jóvenes, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, amenaza, países en vía de desarrollo, Cáncer de hígado
Abstract: Hepatocellular carcinoma (HCC), according to the canonical clinical epidemiology, is found predominantly in men over 40 in age. However, we have described in Peru an unusually younger HCC patient population harboring unique clinical and molecular features such as an explosive tumor growth in non-cirrhotic liver. To date, ethnoanthropological, biogeographical, or socioeconomic evidence that may explain such dramatic variation in the clinical presentation of the tumor affecting younger people remains unknown. Alarmingly, it appears that this phenomenon would not be restricted to Peru, but can be found in other low- and middle-income countries. Therefore, it is urgent to join efforts to prevent an increase in this divergent form of liver cancer., El carcinoma hepatocelular (CHC), según la epidemiología clínica canónica, se encuentra predominantemente en hombres mayores de 40 años. Sin embargo, hemos descrito en el Perú una población de pacientes inusualmente más joven de pacientes con CHC, el mismo que presenta características clínicas y moleculares únicas, como un crecimiento tumoral explosivo en hígado no cirrótico. Hasta la fecha, se desconocen evidencias etno-antropológicas, bio-geográficas o socio-económicas que puedan explicar una discrepancia tan dramática en la presentación clínica de esta neoplasia en nuestro medio. Es alarmante el hecho que este fenómeno al parecer no estaría restringido al Perú, sino que se podría encontrarse en otros países de ingresos bajos y medianos. Por ello, es urgente sumar esfuerzos para evitar el aumento de esta forma divergente de cáncer de hígado.
Published: 2022
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28. List of contributors

Author: Fozia Abasi, Roula M. Abdel-Massih, Elora Aubert, Agnès Aubouy, Julián Cabrera-Barraza, Aissata Camara, José Cerra-Dominguez, Kitti Wing Ki Chan, François Chassagne, Xiaoyan Chen, Bruno David, Marco Nuno De Canha, Eric Deharo, Tanyaradzwa Tiandra Dembetembe, Adama Dénou, Fredyc Díaz-Castillo, Marc El Beyrouthy, Pierre Fechter, Lydia Gibango, Bertrand Graz, Mohamed Haddad, Mahamane Haïdara, Avni Hajdari, Joëlle Houriet, Joshua J. Kellogg, Nadia Khalid, Muhammad Faraz Khan, Quenton Kritzinger, Namrita Lall, Samantha Rae Loggenberg, Guillaume Marti, Zia Ur Rehman Mashwani, Behxhet Mustafa, Andrés Felipe Oliveros-Díaz, Carel B. Oosthuizen, Sergio Ortiz, Romina Pacheco, Yina Pájaro-González, Jiangnan Peng, Minhua Peng, Chiobouaphong Phakeovilay, Véronique Pitchon, Cassandra L. Quave, Naveed Iqbal Raja, Rokia Sanogo, Seethapathy G. Saroja, Jonathan L. Seaman, Sarah Shabih, Danielle Twilley, Remya Unnikrishnan, Santhosh Kumar J. Urumarudappa, Marieke Vansteelandt, Subhash G. Vasudevan, Thomas Vial, Catherine Vonthron, Rahmat Wali, Satoru Watanabe, and Jean-Luc Wolfender
Published: 2022
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29. Antiviral potential of medicinal plants: a case study with guava tree against dengue virus using a metabolomic approach

Author: Thomas Vial, Chiobouaphong Phakeovilay, Satoru Watanabe, Kitti Wing Ki Chan, Minhua Peng, Eric Deharo, François Chassagne, Subhash G. Vasudevan, and Guillaume Marti
Published: 2022
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30. Zootherapeutic uses of animals excreta: the case of elephant dung and urine use in Sayaboury province, Laos

Author: Eric Deharo, Sabrina Krief, Duffillot Sébastien, Palamy Sysay, Lamxay Vichith, Chithdavone Her, Phommachack Kongchack, Jean-Marc Dubost, Musée National d'Histoire Naturelle de Luxembourg (MNHN), and Representation du Laos (IRD)
Subjects: Cultural Studies, Health (social science), Elephants, Context (language use), Urine, Zoonotic transmission, 01 natural sciences, Elephas maximus, [SHS]Humanities and Social Sciences, Other systems of medicine, 03 medical and health sciences, Health problems, Feces, Lao PDR, Zootherapy, Asian elephant, Environmental health, Animals, 030304 developmental biology, Dung beetle, 2. Zero hunger, Faeces, 0303 health sciences, biology, Transmission (medicine), Research, Botany, biology.organism_classification, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, One Health, Complementary and alternative medicine, Laos, QK1-989, Threatened species, Medicine, Traditional, General Agricultural and Biological Sciences, RZ201-999
Abstract: BackgroundDespite a widespread aversion towards faeces and urine, animal excreta are used in traditional medicine in many countries since centuries, but records are scattered and few therapeutic uses have been accurately documented while in the current context of emerging zoonoses such records may be of major interest.MethodologyIn this study, we investigated the therapeutic uses that mahouts in Xayaboury province, Lao PDR make of elephant urine and faeces as well as of the brood chamber that beetles (Heliocopris dominus) fashion from elephant dung. Semi-structured interviews were conducted with mahouts on elephant diet, health problems and responses to disease, andwhether they use elephant products. Data were supplemented by interviews with traditional healers.ResultsSeven respondents reported the use of elephant urine in ethnoveterinary care for elephants and in human medicine in case of diabetes and otitis. 25 respondents reported therapeutic use of elephant faeces (EF) and elephant dung beetle brood chambers. The major indications are gastrointestinal and skin problems. Macerations or decoctions are drunk or used externally as a lotion. The mahouts attribute the therapeutic effectiveness of EFs to their content which includes the remains of many species from the elephant diet which they consider to be medicinal.DiscussionThe indications of these uses are consistent with pharmacological and clinical studies highlighting the properties of different animals’ urine and faeces and their curative potential tested in vivo. The acknowledgement by the mahouts of medicinal properties of elephant faecal bolus contrasts with the rare justifications of animal material use recorded in zootherapeutic studies, which falls within the symbolic domain. However, numerous studies highlight the preponderant role of the microbiota in physiological processes, raising the hypothesis of a curative action of EF, by rebalancing the user’s microbiota.ConclusionThe therapeutic uses of EF preparations despite their possible curative properties are a potential source of zoonotic transmission from elephants to humans. In the current context of globalisation of trade which favours the emergence of zoonoses and in relation with the issue of One Health, it becomes crucial to further document the zootherapeutic practices to prevent emerging diseases. As elephants and local related ethnoethological knowledge are threatened, documenting them is urgent to contribute to their preservation.
Published: 2021
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31. The Threat of Multiple Liver Carcinogens in the Population of Laos: A Review

Author: Pascal Pineau, Agnès Marchio, Eric Deharo, Philavanh Sitbounlang, Phimpha Paboriboune, Cheriet Rauline, Samia, Collaborative Consortium for the early detection of Liver Cancer - COCLICAN - - H2020-MSCA-RISE-20182018-11-01 - 2022-10-31 - 823935 - VALID, Ministry of Health [Laos], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Philavanh Sitbounlang is supported by the European Union’s Horizon 2020 Marie Sklodowska-Curie Actions MSCA—Research and Innovation Staff Exchange—RISE under grant agreement No 823935., We are grateful to Elizabeth Elliott for editorial assistance and constructive criticisms. The authors would like to thank Jean Marc Dubost for the photo of artisanal alcohol production device, taken in Sayaboury Province, Laos., European Project: 823935,H2020-MSCA-RISE-2018,COCLICAN(2018), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)
Subjects: 0301 basic medicine, medicine.medical_specialty, mutagens, primary liver cancer, hepatitis virus, [SDV]Life Sciences [q-bio], Population, 03 medical and health sciences, 0302 clinical medicine, Environmental health, medicine, Opisthorchis viverrini, education, 2. Zero hunger, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, Liver cell, Incidence (epidemiology), Public health, hepatocellular carcinoma, Liver fluke, Hepatitis B, medicine.disease, biology.organism_classification, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030211 gastroenterology & hepatology, Liver cancer, business, cholangiocarcinoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Laos is a landlocked country in South East Asia, ranking fifth for primary liver cancer incidence worldwide. Risk factors that might explain this worrying situation are poorly known. We conducted a review of the literature concerning the etiologies of terminal liver diseases in Laos. A double infectious burden with hepatitis B and C viruses and the liver fluke Opisthorchis viverrini seems to be the main cause of the high liver cancer incidence. Moreover, it was also suggested that mutagenic substances frequently found in tobacco, alcoholic beverages, fermented fish, and mold-contaminated cereals or nuts, which are all substances heavily consumed by Lao people, lead to the accumulation of DNA mutations in the liver cell genome causing tumor processes. However, the respective proportions of liver cancer cases attributable to each category of infections and substances consumed, as well as the histological nature of the neoplasia are still not precisely documented in Laos. The international medical and scientific communities as well as public health stakeholders should urgently consider the alarming situation of liver health in Laos to stimulate both research and subsequent implementation of prevention policies.
Published: 2021
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32. Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle

Author: Thomas Vial, Julien Pompon, Dorothée Missé, Wei-Lian Tan, Guillaume Marti, Eric Deharo, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Duke-NUS Medical School [Singapore], Interhuman Arbovirus Transmission (MIVEGEC-iHAT), Biologie des infections virales: Emergence, DIFfusion, Impact, Contrôle, Elimination (EDIFICE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)
Subjects: replication, viruses, Cell, Phospholipid, mosquito, Genome, Viral, Mosquito Vectors, Dengue virus, Biology, Virus Replication, medicine.disease_cause, Virus, Cell Line, Dengue fever, 03 medical and health sciences, chemistry.chemical_compound, Aedes, medicine, Animals, Humans, Endomembrane system, Vector (molecular biology), Phospholipids, phospholipid, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Cell Membrane, 030302 biochemistry & molecular biology, Dengue Virus, Biological Sciences, biochemical phenomena, metabolism, and nutrition, Lipid Metabolism, medicine.disease, dengue, metabolomics, 3. Good health, Cell biology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, medicine.anatomical_structure, chemistry, Insect Proteins, RNA, Viral, RNA Interference, lipids (amino acids, peptides, and proteins), Viral genome replication, Metabolic Networks and Pathways
Abstract: Dengue virus (DENV) subdues cell membranes for its cellular cycle by reconfiguring phospholipids in humans and mosquitoes. Here, we determined how and why DENV reconfigures phospholipids in the mosquito vector. By inhibiting and activating the de novo phospholipid biosynthesis, we demonstrated the antiviral impact of de novo–produced phospholipids. In line with the virus hijacking lipids for its benefit, metabolomics analyses indicated that DENV actively inhibited the de novo phospholipid pathway and instead triggered phospholipid remodeling. We demonstrated the early induction of remodeling during infection by using isotope tracing in mosquito cells. We then confirmed in mosquitoes the antiviral impact of de novo phospholipids by supplementing infectious blood meals with a de novo phospholipid precursor. Eventually, we determined that phospholipid reconfiguration was required for viral genome replication but not for the other steps of the virus cellular cycle. Overall, we now propose that DENV reconfigures phospholipids through the remodeling cycle to modify the endomembrane and facilitate formation of the replication complex. Furthermore, our study identified de novo phospholipid precursor as a blood determinant of DENV human-to-mosquito transmission.
Published: 2020
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33. Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes

Author: Alexis Valentin, Cécile Minet, Eric Deharo, María Helena Arias, Isabelle Fabing, Sandra Bourgeade-Delmas, Isabelle Chantal, Jonathan Sorres, Véronique Eparvier, David Berthier, Giovanny Garavito, Silvia Galiano, Miguel Quiliano, Didier Stien, Ignacio Aldana, Universidad Nacional de Colombia [Bogotà] (UNAL), Universidad Peruana de Ciencias Aplicadas (Lima) (UPC), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides (UMR INTERTRYP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bordeaux (UB), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), PIERRE FABRE-EDF (EDF)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Universidad de Navarra [Pamplona] (UNAV), Representation du Laos (IRD), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université de Bordeaux (UB)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)
Subjects: Plasmodium, [SDV]Life Sciences [q-bio], Expérimentation in vivo, 030308 mycology & parasitology, Mice, 0302 clinical medicine, Chloroquine, Chlorocebus aethiops, Babesia divergens, ComputingMilieux_MISCELLANEOUS, Leishmania, 0303 health sciences, biology, Contrôle de maladies, General Medicine, Amino Alcohols, Expérimentation in vitro, 3. Good health, Infectious Diseases, Treatment Outcome, S50 - Santé humaine, Parasitose, medicine.drug, Trypanosoma, Cell Survival, 030231 tropical medicine, Plasmodium falciparum, Antiprotozoal Agents, Babesia, 03 medical and health sciences, Plasmodium falciparum gametocytes, parasitic diseases, medicine, Gametocyte, Animals, Protozoa, Amastigote, Vero Cells, Efficacité, Life Cycle Stages, Protozoan Infections, General Veterinary, biology.organism_classification, Virology, Disease Models, Animal, Insect Science, Antiprotozoan, Parasitology, Alsinol, [CHIM.OTHE]Chemical Sciences/Other
Abstract: Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models. Departamento Administrativo de Ciencia, TecnologÃa e InnovaciÃ³n (COLCIENCIAS) Revisión por pares
Published: 2020
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34. Takamalaimë, Wayana malaleja epit: une perspective holistique pour l’étude de Psidium acutangulum Mart. Ex DC. (Myrtaceae), un remède antipaludique des amérindiens wayana de Guyane

Author: Emeline Houël, Flore Nardella, Marie Fleury, Valérie Jullian, Alexis Valentin, Catherine Vonthron-Sénécheau, Pascal Villa, Adeline Obrecht, Matthias Kaiser, Eliane Bourreau, Guillaume Odonne, Véronique Eparvier, Genevieve Bourdy, Eric Deharo, Stien, D., Ecologie des forêts de Guyane (UMR ECOFOG), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Institut de Parasitologie et de Pathologie Tropicale (IPPTS), Université de Strasbourg (UNISTRA), Patrimoines Locaux et Gouvernance (PALOC), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), University of Basel (Unibas), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Laboratoire Ecologie, évolution, interactions des systèmes amazoniens (LEEISA), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), PIERRE FABRE-EDF (EDF)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Patrimoines locaux, Environnement et Globalisation (PALOC), Sorbonne Université (SU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens (LEEISA), Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Fleury, M., Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [CHIM]Chemical Sciences, [SDV.BID]Life Sciences [q-bio]/Biodiversity, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2020

35. A Seven-Year Retrospective Study on the Surveillance of Hepatitis B in Laos

Author: Philavanh Sitbounlang, Eric Deharo, François Chassagne, Sengaloun Soundala, Phimpha Paboriboune, Stéphane Bertani, François-Xavier Babin, Thomas Vial, Davone Sengmanothong, Pascal Pineau, Paul Dény, Nicolas Steenkeste, Center of Infectiology Lao-Christophe Mérieux [Vientiane] (CILM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Fondation Mérieux, Université Paris 13 (UP13), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Me ́rieux for providing nancial support and to medical sta and patients. Phimpha Paboriboune was sup- ported by CILM, IRD, Campus France, and Fondation Me ́rieux. Franc ̧ois Chassagne was supported by Fonda- tion pour la Recherche Me ́dicale (FDM20140731352), Paul Sabatier University of Toulouse, and the ird Cancer Plan of the French National Alliance for Life Sciences and Health (ENV201408), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Article Subject, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Medicine, lcsh:RC799-869, Hepatology, business.industry, Incidence (epidemiology), [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, Hepatitis B, medicine.disease, 3. Good health, Vaccination, Laos, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Liver function, business, Liver cancer, Viral load, Research Article, Cohort study
Abstract: Objective. Lao PDR is one of the most highly endemic countries for hepatitis B in Asia and the second country for liver cancer incidence. Therefore, the follow-up of infected individuals through predictive serological markers is of utmost importance to monitor the progression of the pathology and take the decision on treatment. Methods. A retrospective-descriptive cohort study was conducted on 3,857 HBV-infected patients. Information about infection status (viral load, VL), liver function (aminotransferases), and treatments was recorded. Results. M/F sex ratio was 1.77 for a median age of 37. Patients under 37 displayed higher VL than older ones and men had higher VL than women. Initial VL ranged from 13 IU/mL. Median aminotransferase values were 45.5 U/L for ALAT and 44 U/L for ASAT, ranging from 2,000 U/L. Men had higher aminotransferase than women. Globally 20% of patients received treatment (mainly immunostimulant and reverse-transcriptase inhibitors); 11% had high levels of VL and liver enzymes, but only 2% of them were treated. Conclusion. Public health decisions should be taken urgently to rationalise vaccination and provide fair access to early diagnosis and treatment; otherwise the burden of HBV-associated diseases will be overwhelming for Laos in the near future.
Published: 2018
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36. Quassia 'biopiracy' case and the Nagoya Protocol: A researcher's perspective

Author: Geneviève Bourdy, Eric Deharo, Catherine Aubertin, Valérie Jullian, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Patrimoines locaux, Environnement et Globalisation (PALOC), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Sorbonne Université (SU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)
Subjects: INDIANS, 0301 basic medicine, RESOURCES, [SDV]Life Sciences [q-bio], NATURAL BIOACTIVE COMPOUNDS, 030106 microbiology, MULTIDISCIPLINARY APPROACH, Context (language use), AMARA L. SIMAROUBACEAE, Indigenous, FRENCH-GUIANA, Patents as Topic, 03 medical and health sciences, Misconduct, Politics, SEARCH, Drug Discovery, Medicine, Nagoya Protocol, Traditional knowledge, Ratification, SIMALIKALACTONE-D, Pharmacology, Plants, Medicinal, business.industry, Biodiversity, French Guiana, Quassia, 030104 developmental biology, Law, BOLIVIA, ANTIMALARIAL ACTIVITY, business, Allegation
Abstract: International audience; Biopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Développement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors' arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation.
Published: 2017
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37. On hepatocellular carcinoma in South America and early-age onset of the disease

Author: Eric Deharo, Pascal Pineau, Eloy Ruiz, Stéphane Bertani, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto Nacional de Enfermedades Neoplasicas [Lima, Pérou] (INEN), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), This work was supported by the French National Alliance for Life Sciences and Health [grant number ENV201408], the French National League Against Cancer, Paris, France, and the French National Research Institute for Sustainable Development, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), CCSD, Accord Elsevier, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: Adult, Male, Cancer risk factor, Pediatrics, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, Peru, medicine, Hepatitis B virus HBV, Humans, East Asia, Hepatitis B virus (HBV), Age of Onset, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Low- and middle-income countries, Hepatology, Indigenous people, business.industry, Liver Neoplasms, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Low and middle income countries, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, Female, Liver cancer, business, Global health transition
Abstract: International audience; Hepatocellular carcinoma (HCC) is one of the most predominant tumor types worldwide, being particularly prevalent in sub-Saharan Africa and East Asia. However, HCC is inexplicably underreported in South America, despite unsettling clinical epidemiological trends of the disease on this continent. Here, we review the current knowledge on HCC presentation in Peru. We emphasize the well-documented occurrence of an early-age nosological form of the disease in Andean descent populations. We further discuss the reasons for such HCC clinical presentation, as well as the implications for liver cancer screening, management, and prevention.
Published: 2019
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38. Dengue virus reduces AGPAT1 expression to alter phospholipids and enhance infection in Aedes aegypti

Author: Benjamin Wong Wei Xiang, Guillaume Marti, Dorothée Missé, Thomas Vial, Eric Deharo, Julien Pompon, Wei-Lian Tan, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Duke-NUS Medical School [Singapore], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: RNA viruses, Physiology, viruses, Dengue virus, Disease Vectors, medicine.disease_cause, Pathology and Laboratory Medicine, Mosquitoes, Biochemistry, Phosphatidate, chemistry.chemical_compound, Guide RNA, Aedes, Medicine and Health Sciences, Biology (General), Phospholipids, 0303 health sciences, 030302 biochemistry & molecular biology, virus diseases, Eukaryota, Lipidome, 1-Acylglycerol-3-Phosphate O-Acyltransferase, Lipids, 3. Good health, Body Fluids, Insects, Nucleic acids, Infectious Diseases, Blood, Medical Microbiology, Acyltransferase, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Insect Proteins, Pathogens, Anatomy, Research Article, Cell Physiology, Arthropoda, QH301-705.5, Immunology, Aedes aegypti, Mosquito Vectors, Biology, Microbiology, Host-Parasite Interactions, 03 medical and health sciences, Viral envelope, Virology, Genetics, medicine, Animals, Metabolomics, Molecular Biology, Microbial Pathogens, 030304 developmental biology, Phosphatidylethanolamine, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Flaviviruses, Organisms, Biology and Life Sciences, Cell Biology, RC581-607, biochemical phenomena, metabolism, and nutrition, Dengue Virus, biology.organism_classification, Invertebrates, Insect Vectors, Cell Metabolism, Species Interactions, Metabolism, chemistry, RNA, Parasitology, Immunologic diseases. Allergy
Abstract: More than half of the world population is at risk of dengue virus (DENV) infection because of the global distribution of its mosquito vectors. DENV is an envelope virus that relies on host lipid membranes for its life-cycle. Here, we characterized how DENV hijacks the mosquito lipidome to identify targets for novel transmission-blocking interventions. To describe metabolic changes throughout the mosquito DENV cycle, we deployed a Liquid chromatography–high resolution mass spectrometry (LC-HRMS) workflow including spectral similarity annotation in cells, midguts and whole mosquitoes at different times post infection. We revealed a major aminophospholipid reconfiguration with an overall early increase, followed by a reduction later in the cycle. We phylogenetically characterized acylglycerolphosphate acyltransferase (AGPAT) enzyme isoforms to identify those that catalyze a rate-limiting step in phospholipid biogenesis, the acylation of lysophosphatidate to phosphatidate. We showed that DENV infection decreased AGPAT1, but did not alter AGPAT2 expression in cells, midguts and mosquitoes. Depletion of either AGPAT1 or AGPAT2 increased aminophospholipids and partially recapitulated DENV-induced reconfiguration before infection in vitro. However, only AGPAT1 depletion promoted infection by maintaining high aminophospholipid concentrations. In mosquitoes, AGPAT1 depletion also partially recapitulated DENV-induced aminophospholipid increase before infection and enhanced infection by maintaining high aminophospholipid concentrations. These results indicate that DENV inhibition of AGPAT1 expression promotes infection by increasing aminophospholipids, as observed in the mosquito’s early DENV cycle. Furthermore, in AGPAT1-depleted mosquitoes, we showed that enhanced infection was associated with increased consumption/redirection of aminophospholipids. Our study suggests that DENV regulates aminophospholipids, especially phosphatidylcholine and phosphatidylethanolamine, by inhibiting AGPAT1 expression to increase aminophospholipid availability for virus multiplication., Author summary Dengue is endemic in tropical and subtropical regions, and has now encroached onto temperate regions because of the geographic expansion of its vector, Aedes aegypti. In the absence of effective vaccine and curative drug, the sole intervention relies on containment strategies using insecticide. However, occurrence of insecticide resistance diminishes vector control efficacy. Here, we explore the nascent field of mosquito metabolomics as part of our discovery effort for new transmission-blocking targets. Dengue virus (DENV) relies on host metabolome, specifically the lipid membrane to complete its life-cycle. However, little is known about how DENV subverts the mosquito physiology. Using high-resolution mass spectrometry, we described metabolic changes incurred by DENV throughout the mosquito cycle, from cellular replication onset to systemic infection. Membrane phospholipids were highly reconfigured and were associated with reduced expression of AGPAT1, an enzyme involved in their biogenesis. AGPAT1 depletion partially recapitulated DENV-induced metabolic reconfiguration and enhanced infection by maintaining high phospholipid concentrations. These phospholipids were then consumed/redirected later in the mosquito DENV cycle. Our work comprehensively describes metabolic changes associated with DENV infection. In addition, we reveal how DENV subdues the lipidome for its benefit by demonstrating the role of phospholipids in mosquito infection.
Published: 2019
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39. Forest Fevers: traditional treatment of malaria in the southern lowlands of Laos

Author: Vichith Lamxay, Chantanom Manithip, Eric Deharo, Elizabeth Elliott, Agnès Aubouy, Geneviève Bourdy, Kongmany Sydara, François Chassagne, Juan Antonio Torres, Outhay Souvanasy, and Phaiboun Sythamala
Subjects: Male, medicine.medical_specialty, Plasmodium, Fever, Plasmodium vivax, Forests, 03 medical and health sciences, 0302 clinical medicine, Medicinal plants, Drug Discovery, Health care, parasitic diseases, Emic fever classification, medicine, Nosology, Humans, Medical prescription, Socioeconomics, Traditional healers, Medicine, African Traditional, 030304 developmental biology, Aged, Pharmacology, Aged, 80 and over, 0303 health sciences, Plants, Medicinal, biology, business.industry, Public health, Traditional medicine, Middle Aged, medicine.disease, biology.organism_classification, Artemisinins, Malaria, Voucher, Geography, Herbarium, Laos, 030220 oncology & carcinogenesis, Plant Preparations, Herbal medicine, business, Phytotherapy
Abstract: Ethnopharmacological relevance Malaria is still a highly challenging public health issue in southern Lao PDR, with increasing cases of artemisinin resistance and Plasmodium vivax infections which are more complicated to treat. Traditional medicine has a long history of use in Laos, and is primarily practised by traditional village healers, who possess unique bodies of transmitted knowledge focused on herbal prescriptions, including those for the treatment of malaria. Villagers also use plants for healthcare in the home. The aim of the study is to document local fever concepts and use of herbal remedies, and examine whether they may have potential as complementary treatments against malaria. Materials and methods The study took place in Champasak province in the far south of Laos, in primarily lowland areas. First, 35 traditional healers across the 10 districts of the province were interviewed to elicit details about knowledge and treatment of fevers. Second, a household survey was conducted in a village in a malaria-endemic area; 97 households were interviewed on fever incidence, differentiation, treatment-seeking behaviour and knowledge of plant-based remedies for fevers. Plants indicated by both healers and villagers were collected and voucher specimens deposited in the herbarium of the National University of Laos for identification. Results Malaria is a well-known pathology among the healers and villagers of lowland Champasak province; biomedical treatments are preferentially used, but traditional medicine is a popular complementary method, especially in chronic cases with additional symptoms. 30 different fever types were recorded, which were usually named symptomatically, and grouped into 12 categories. Some were described as forms of malaria, which was conceived as a dynamic, changing pathology affecting many body systems. Healers formulate treatments based on symptoms and the person's constitution, and with the intention of creating specific pharmacological actions associated with temperature or flavours. 11 of the healers gave prescriptions for malaria (27 in total), including 47 identified plant species. The most-used plants (4 or more use-reports) were also the most cited in the literature for use against malaria, demonstrating a correspondence between Lao healers and other traditional medical systems. Furthermore, some of these species show promising results for future research, especially Amorphophallus paeniifolius (Dennst.) Nicolson and Alocasia macrorrhizos (L.) G. Don. Conclusion Traditional healers are important actors in the treatment of malaria in southern Laos, and herbal remedies should be evaluated further by the use of reverse treatment outcome trials, especially those which may be of use as complementary remedies in treating P. vivax. Initiatives on knowledge transmission, medicinal plant conservation and healthcare integration are also urgently needed.
Published: 2019

40. From plant selection by elephants to human and veterinary pharmacopeia of mahouts in Laos

Author: Chanthanom Manithip, Eric Deharo, Michael Falshaw, Sabrina Krief, Vichith Lamxay, Jean-Marc Dubost, Musée National d'Histoire Naturelle de Luxembourg (MNHN), Representation du Laos (IRD), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Eco-Anthropologie et Ethnobiologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), National University of Laos, Elephant Conservation Center, University of Health Sciences [Vientiane, Laos] (UHS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: Health Knowledge, Attitudes, Practice, Veterinary medicine, [SDV]Life Sciences [q-bio], Elephants, MESH: Health Knowledge, Attitudes, Practice, MESH: Plants, Medicinal, Animal Diseases, [SHS]Humanities and Social Sciences, Health problems, 0302 clinical medicine, Feeding behavior, Surveys and Questionnaires, MESH: Behavior, Animal, Drug Discovery, Health care, MESH: Animals, ComputingMilieux_MISCELLANEOUS, MESH: Aged, 2. Zero hunger, 0303 health sciences, MESH: Middle Aged, Behavior, Animal, Middle Aged, Geography, Laos, MESH: Elephants, 030220 oncology & carcinogenesis, Ethnobotany, MESH: Feeding Behavior, Female, Adult, Health knowledge, MESH: Phytotherapy / veterinary, 03 medical and health sciences, Animals, Humans, MESH: Indigenous Peoples, MESH: Surveys and Questionnaires, Indigenous Peoples, Aged, 030304 developmental biology, MESH: Animal Diseases / drug therapy, Pharmacology, Plants, Medicinal, MESH: Humans, business.industry, MESH: Adult, Feeding Behavior, MESH: Laos, business, MESH: Female, Phytotherapy
Abstract: Ethnopharmacological relevance To what extent has animal observation contributed to the development of human pharmacopeias? We approach this question here through the study of mahouts’ knowledge regarding the responses by elephants to their health problems, and the human medicinal uses of plants and the care of domestic animals that result from their observations. Materials and methods 32 mahouts were interviewed in Thongmyxay district and 28 at the Elephant Conservation Center in the province of Xayabury. Interviews focused on the elephants’ diet, health problems, plant items they consume in particular physiological or pathological contexts and the treatments that mahouts provide them. For each plant mentioned, the part of the plant consumed and mode of preparation and administration if used by mahouts were recorded. Species samples were then collected and later identified by specialists. Results 114 species were recorded as being consumed by elephants during interviews with mahouts and forest outings with them to collect samples. Twenty species were identified as used by elephants in particular pathological conditions or physiological states. According to interviewed mahouts, the consumption of certain plants improves the health of the elephant. We observed clear convergences between the observations interpreted by the mahouts as self-medication behaviour from elephants and their own medicinal practices (for human and veterinary purposes). Conclusion Beyond a mere reproduction of elephant self-medication behaviours observed, the human or veterinary medicinal cares derived from these observations are the result of complex arrangements integrating all available medicinal and conceptual resources into elaborate preparations. We recommend that mahouts' knowledge about traditional medicinal care given to elephants be further compiled, as it could have a beneficial impact on veterinary health care provided in elephant resorts and elephants’ well-being.
Published: 2019
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41. Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration

Author: Giovanny Garavito, Ben M. Dunn, Silvia Galiano, David W. Wright, Miguel Quiliano, Eric Deharo, Adriana Pabón, Nathan E. Goldfarb, Adela López de Cerain, Ignacio Aldana, Adela Mendoza, Isabelle Fabing, Kim Y. Fong, Ariane Vettorazzi, Silvia Pérez-Silanes, Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Vanderbilt University [Nashville], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], University of Florida [Gainesville] (UF), Southern California University of Health Sciences, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universidad Nacional de Colombia [Bogotà] (UNAL), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Southern California University of Health Sciences (SCU), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), and Université de Toulouse (UT)
Subjects: 0301 basic medicine, Hemozoin inhibition, Antimalarial, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Parasitemia, Pharmacology, medicine.disease_cause, 01 natural sciences, Antiplasmodial, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mannich reaction, Pharmacology (medical), Malaria, Falciparum, biology, Chemistry, Regular Article, Amino Alcohols, Arylamino alcohol, 3. Good health, Treatment Outcome, Infectious Diseases, Biochemistry, Pharmacophore, Drug-Related Side Effects and Adverse Reactions, In silico, Plasmodium falciparum, lcsh:Infectious and parasitic diseases, Plasmepsin II enzyme, Antimalarials, Inhibitory Concentration 50, Structure-Activity Relationship, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, medicine, Animals, Potency, lcsh:RC109-216, IC50, biology.organism_classification, medicine.disease, Survival Analysis, 0104 chemical sciences, Disease Models, Animal, 010404 medicinal & biomolecular chemistry, 030104 developmental biology, Parasitology, Genotoxicity
Abstract: Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 ≤ 0.19 μM) and multidrug resistant (FCR-3 IC50 ≤ 0.40 μM and C235 IC50 ≤ 0.28 μM) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed. Notably, compound 22 displays excellent parasitemia reduction (98 ± 1%), and complete cure with all treated mice surviving through the entire period with no signs of toxicity. One important factor is the agreement between in vitro potency and in vivo studies. Target exploration was performed; this chemotype series exhibits an alternative antimalarial mechanism., Graphical abstract Image 1, Highlights • New aryl-substituted propanol derivatives (APD) show promising antimalarial activity. • γ-amino alcohol moiety is significant antimalarial chemotype. • Compound 22 displays excellent in vivo parasitemia reduction (98%) and complete cure. • APD are active against drug sensitive and multidrug resistant strains.
Published: 2016
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42. Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden

Author: Sandro Casavilca, Pascal Pineau, Juan Pablo Cerapio, Anne Dejean, Eloy Ruiz, Luis Cano, Agnès Marchio, Eric Deharo, Stéphane Bertani, Benoit Terris, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Instituto Nacional de Enfermedades Neoplasicas [Lima, Pérou] (INEN), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de cytologie pathologiques [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), This study was funded by the French National League against Cancer (team label LNCC) and Odyssey-RE, E.D., S.B., and P.P. were supported by the Third Cancer Plan, ITMO Cancer of the French National Alliance for Life Sciences and Health (ENV201408), J.P.C. was a recipient of a doctoral fellowship from the Peruvian National Council for Science and Technology (212-2015-FONDECYT), L.C. was a recipient of a doctoral fellowship from French National Research Institute for Sustainable Development (IRD) (EMHE-ARTS-2016-878573B), and L.C., E.R., and S.C. were supported by the Young Research Teams Associated with IRD Program (INCAncer)., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Bertani, Stéphane, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, Male, DNA Repair, Hepatocellular carcinoma, lcsh:Medicine, medicine.disease_cause, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Peru, Medicine, genetics, Dna viral, lcsh:Science, Child, Early onset, Aged, 80 and over, Multidisciplinary, Liver Neoplasms, Middle Aged, Viral Load, 3. Good health, female, Liver, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, Female, Liver cancer, Adult, Hepatitis B virus, Carcinoma, Hepatocellular, Adolescent, DNA repair, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hepatitis B virus DNA, Article, 03 medical and health sciences, Young Adult, Hepatitis B, Chronic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, chronic hepatitis B, Aged, business.industry, lcsh:R, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Virology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, DNA, Viral, Etiology, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, purl.org/pe-repo/ocde/ford#3.04.03 [http], business
Abstract: In Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1–6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas’ indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation.
Published: 2018
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43. Pharmacological activity of Curarea toxicofera in combination with classical antimalarial treatments

Author: Eric Deharo, José Octavio García, Giovanny Garavito, Yinneth Victoria Rodríguez, María Helena Arias, Universidad Nacional de Colombia [Bogotà] (UNAL), and Universidad Nacional de Colombia
Subjects: 0301 basic medicine, Plasmodium, Plasmodium berghei, [SDV]Life Sciences [q-bio], 030106 microbiology, 030231 tropical medicine, Plasmodium falciparum, Artesunate, Parasitemia, Pharmacology, Curarea toxicofera, Menispermaceae, 03 medical and health sciences, chemistry.chemical_compound, Mice, Antimalarials, 0302 clinical medicine, Chloroquine, In vivo, Drug Discovery, medicine, Animals, Drug Interactions, IC50, biology, business.industry, Plant Extracts, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, medicine.disease, In vitro, Artemisinins, 3. Good health, Malaria, chemistry, Ethnopharmacology, Drug Therapy, Combination, business, medicine.drug, Phytotherapy
Abstract: Ethnopharmacological relevance In the Leticia-Amazonas area, Uitoto indigenous people use a preparation of Curarea toxicofera (Wedd) Barneby & Krukoff (Menispermaceae) alone or combined with prescribed medications to prevent and treat malaria. Aim of study To determine the in vitro and in vivo antiplasmodial activity of traditional preparations of Curarea toxicofera alone and in combination with classical antimalarials. Material and Methods The traditional preparation was evaluated in vitro against P. falciparum FCR3 CQ resistant strain, alone and combined. The preparation was further administered orally alone or combined with chloroquine and artesunate in mice infected with Plasmodium berghei ANKA strain on the four-day antimalarial test model. Results The herbal remedy used alone was able to significantly decrease the parasitemia both in vitro (IC50 7.3 µg/ml) and in vivo (ED50 328 mg/Kg) but it was less active than chloroquine (IC50 0.29 µg/ml in vitro and ED50 2.3 mg/Kg/day in vivo), and than artesunate (IC50 0.002 µg/ml and ED50 3.7 mg/Kg/day). Interestingly it presented synergism with chloroquine in vitro (Combination Index: 0.39) and in vivo; and was additive with artesunate in vitro (Combination Index: 0.94) and in vivo. Conclusion The traditional preparation showed potential as an antimalarial and, when used in combination, does not negatively affect the efficacy of the drugs evaluated. Pre-clinical studies should be conducted with a standardized preparation to confirm its efficacy and safety alone and in combination with chloroquine and artesunate.
Published: 2018
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44. Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients

Author: Paul Dény, Philavanh Sitbounlang, Thomas Vial, Pascal Pineau, Eric Deharo, Nicolas Steenkeste, François-Xavier Babin, Stéphane Bertani, Christian Trepo, Phimpha Paboriboune, Center of Infectiology Lao-Christophe Mérieux [Vientiane] (CILM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13), Fondation Mérieux, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Hepacivirus, Liver disease, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, Pegylated interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Global health, Medicine, Aged, 80 and over, HCV incidence, Hepatitis C, Hepatitis C virus (HCV), Middle Aged, Viral Load, 3. Good health, Treatment Outcome, Laos, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, 030211 gastroenterology & hepatology, Female, Viral load, medicine.drug, Research Article, Adult, medicine.medical_specialty, Adolescent, Immunology, Guidelines as Topic, 03 medical and health sciences, Young Adult, Virology, Internal medicine, Humans, Aged, Retrospective Studies, business.industry, Public health, Ribavirin, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, 030104 developmental biology, Antiviral agents, chemistry, Liver function, business
Abstract: International audience; Hepatitis C virus (HCV) is a global health concern, notably in Southeast Asia, and in Laos the presentation of the HCV-induced liver disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients, their infection status (viral load: VL), liver function (aminotransferases) and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6 years for women (13-86 years). The majority of patients (72%) were confirmed positive (VL > 50 IU/mL) and 28% of them had high VL (> 6log10). About 23% of patients had level of aminotransferases indicative of liver damage (> 40 IU/mL); but less than 20% of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff, without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines. However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.
Published: 2018
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45. A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases

Author: Aurélien Amiel, François Chassagne, Mohamed Haddad, Guillaume Marti, Chanthanom Manithip, Geneviève Bourdy, Chiobouaphong Phakeovilay, Eric Deharo, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), University of Health Sciences [Vientiane, Laos] (UHS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: 0301 basic medicine, HepG2, Hepatocellular carcinoma, Southeast asian, Catechin, Anti-proliferative effect, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medicinal plants, Drug Discovery, Biflavonoids, Humans, Metabolomics, Proanthocyanidins, Chrysin, Apigenin, Asia, Southeastern, Pharmacology, Flavonoids, Orthosiphon aristatus, Lamiaceae, Plants, Medicinal, Traditional medicine, biology, Willughbeia edulis, Liver Neoplasms, General Medicine, Hep G2 Cells, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, Oroxylum indicum, Antineoplastic Agents, Phytogenic, Southeast Asia, Apocynaceae, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Bignoniaceae, Ethnopharmacology, Flavanones, Oroxylin A, Andrographis, Diterpenes, Andrographis paniculata
Abstract: International audience; Liver cancer is a major health burden in Southeast Asia, and most patients turn towards the use of medicinal plants to alleviate their symptoms. The aim of this work was to apply to Southeast Asian plants traditionally used to treat liver disorders, a successive ranking strategy based on a comprehensive review of the literature and metabolomic data in order to relate ethnopharmacological relevance to chemical entities of interest. We analyzed 45 publications resulting in a list of 378 plant species, and our point system based on the frequency of citation in the literature allowed the selection of 10 top ranked species for further collection and extraction. Extracts of these plants were tested for their in vitro anti-proliferative activities on HepG2 cells. Ethanolic extracts of Andrographis paniculata, Oroxylum indicum, Orthosiphon aristatus and Willughbeia edulis showed the highest anti-proliferative effects (IC50 = 195.9, 64.1, 71.3 and 66.7 μg/ml, respectively). A metabolomic ranking model was performed to annotate compounds responsible for the anti-proliferative properties of A. paniculata (andrographolactone and dehydroandrographolide), O. indicum (baicalein, chrysin, oroxylin A and scutellarein), O. aristatus (5-desmethylsinensetin) and W. edulis (parabaroside C and procyanidin). Overall, our dereplicative approach combined with a bibliographic scoring system allowed us to rapidly decipher the molecular basis of traditionally used medicinal plants.
Published: 2018
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46. Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives : synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery

Author: Diego A. Nieto-Aco, Xavier Fernàndez-Busquets, Isabelle Fabing, Eric Deharo, Leonardo Bonilla-Ramirez, Ariane Vettorazzi, Giovanny Garavito, Juan C. Pizarro, Adriana Pabón, Kim Y. Fong, Ernest Moles, David W. Wright, Miguel Quiliano, Ignacio Aldana, Silvia Galiano, Adela López de Cerain, Instituto de Salud Tropical, Universidad de Navarra (Pamplona), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], University of Barcelona, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Vanderbilt University [Nashville], Tulane University School of Public Health and Tropical Medicine [New Orleans, LA, USA], Clínica Universidad de Navarra [Pamplona], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Universidad Nacional de Colombia [Bogotà] (UNAL), Department of Endocrinology and Nutrition, Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), and Université de Toulouse (UT)
Subjects: 0301 basic medicine, Cell Survival, Plasmodium berghei, Propanols, In silico, Plasmodium falciparum, 030106 microbiology, Antimalarial, Hsp90, Parasitemia, Antiplasmodial, Propanol, Antimalarials, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Drug Delivery Systems, Parasitic Sensitivity Tests, In vivo, parasitic diseases, Drug Discovery, Multi-stage activity, [CHIM]Chemical Sciences, Animals, Humans, Structure–activity relationship, Cytotoxicity, Pharmacology, Dose-Response Relationship, Drug, Molecular Structure, biology, Chemistry, Organic Chemistry, Hep G2 Cells, General Medicine, biology.organism_classification, In vitro, Arylamino alcohol, 3. Good health, 030104 developmental biology, Biochemistry, Enantiomer separation
Abstract: International audience; Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50s < 0.28 μM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC50s < 0.7 μM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.
Published: 2018
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47. Sacha Inchi Oil (Plukenetia volubilis L.), effect on adherence of Staphylococus aureus to human skin explant and keratinocytes in vitro

Author: Haouaria Belkhelfa, Geneviève Bourdy, Laila Haddioui-Hbabi, Eric Deharo, German Gonzalez-Aspajo, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, FONdation pour le DEveloppement de la REcherche PHARmaceutique - FONDEREPHAR (FRANCE), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: Keratinocytes, Staphylococcus aureus, Cell Survival, [SDV]Life Sciences [q-bio], Human skin, Context (language use), Plukenetia volubilis L, Skin infection, Biology, medicine.disease_cause, Bacterial Adhesion, Cell Line, Sacha Inchi Oil, Keratinocytes cells, chemistry.chemical_compound, Drug Discovery, Botany, medicine, Humans, Plant Oils, Coco, Trypticase soy agar, Skin, Pharmacology, integumentary system, Traditional medicine, Euphorbiaceae, Human skin explant, 15. Life on land, medicine.disease, biology.organism_classification, medicine.anatomical_structure, chemistry, Dietary Supplements, Keratinocyte, Plukenetia volubilis
Abstract: Ethnopharmacological relevance Plukenetia volubilis L. (Euphorbiaceae) is a domesticated vine distributed from the high-altitude Andean rain forest to the lowlands of the Peruvian Amazon. Oil from the cold-pressed seeds, sold under the commercial name of Sacha Inchi Oil (SIO) is actually much in favour because it contains a high percentage of omega 3 and omega 6, and is hence used as a dietary supplement. SIO is also used traditionally for skin care, in order to maintain skin softness, and for the treatment of wounds, insect bites and skin infections, in a tropical context where the skin is frequently damaged. Aims of the study This study was designed in order to verify whether the traditional use of SIO for skin care would have any impact on Staphylococcus aureus growth and skin adherence, as S. aureus is involved in many skin pathologies ( impetigo, folliculitis, furuncles and subcutaneous abscesses) being one if the main pathogens that can be found on the skin. Therefore, our objective was to assess SIO bactericidal activity and interference with adherence to human skin explants and the keratinocyte cell line. Cytotoxicity on that cells was also determined. The activity of SIO was compared to coconut oil (CocO), which is widely used for skin care but has different unsaturated fatty acids contents. Materials and methods Laboratory testing with certified oil, determined antibacterial activity against radio labelled S. aureus . Cytotoxic effects were measured with XTT on keratinocyte cells and with neutral red on human skin explants; phenol was used as cytotoxic control. Adherence assays were carried out by mixing H3-labelled S. aureus bacteria with keratinocyte cells and human skin explants, incubated with oils 2 h before (to determine the inhibition of adherence, assimilated to a preventive effect) or 2 h after the contact of the biological material with S. aureus (to assess the detachment of the bacteria, assimilated to a curative effect). Residual radioactivity measured after washings made it possible to determine the adherence intensity. Bactericidal effect was determined by colony counting on trypticase soy agar. Results Laboratory assays showed that SIO and CocO, tested undiluted, were not cytotoxic on keratinocytes nor human explants and were not bactericidal neither. SIO was more active as antiadherent (preventive) than CocO on keratinocytes. There was no significant difference between detachment effects (curative) of both oils on keratinocytes but SIO was almost 5 times more active on the detachment of S. aureus from human skin explants. Conclusion From that study it can be concluded that the use of SIO on dermal cells is safe and efficient in the inhibition of S. aureus adherence. Our results tend to support the traditional use of undiluted SIO in skin care.
Published: 2015
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48. Adaptation and optimization of a fluorescence-based assay for in vivo antimalarial drug screening

Author: Eric Deharo, Giovanny Garavito, Alexis Valentin, María Helena Arias, Universidad Nacional de Colombia [Bogotà] (UNAL), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)
Subjects: Male, 0301 basic medicine, Plasmodium berghei, [SDV]Life Sciences [q-bio], 030231 tropical medicine, 030106 microbiology, Microbial Sensitivity Tests, Diamines, Biology, Azure Stains, Fluorescence, Giemsa stain, Antimalarials, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Lysis buffer, parasitic diseases, Animals, Benzothiazoles, Organic Chemicals, Whole blood, Pharmacology, General Veterinary, SYBR Green I, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, Molecular biology, 3. Good health, Staining, Malaria, Infectious Diseases, chemistry, Insect Science, Quinolines, Parasitology, Cytometry
Abstract: International audience; The in vivo efficacy of potential antimalarials is usually evaluated by direct microscopic determination of the parasitaemia of Plasmodium-infected mice on Giemsa-stained blood smears. This process is time-consuming, requires experienced technicians and is not automatable. Therefore, we optimized a SYBR Green I (SYBRG I) fluorescence-based assay to fluorometers commonly available in many research laboratories. This technique was originally developed to assess parasitaemia in humans by cytometry. We defined optimal conditions with Plasmodium berghei-infected mice, standard lysis buffer (Tris, EDTA, saponin and Triton), whole blood cells and 2 h staining incubation with SYBRG I 2X. The fluorescence background generated by uninfected whole blood cells was low (around 4.6%), and the linearity high (r 2 = 0.96), with parasitaemia ranging from 1.4 to 60%. The Bland-Altman plot showed a strong correlation between SYBRG I and Giemsa gold standard method; Z'-factor was >0.5. These findings suggest that our fluorescence-based assay is suitable for in vivo antimalarial drug assessment in a malaria murine model. It can help to overcome the human bias found with microscopic techniques.
Published: 2017
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49. Treatment and management of liver diseases by Khmer traditional healers practicing in Phnom Penh area, Cambodia

Author: Eric Deharo, Hieng Punley, François Chassagne, Geneviève Bourdy, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), University of Health Sciences [Phnom-Penh, Cambodia] (UHS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)
Subjects: HEPATITIS-B, [SDV]Life Sciences [q-bio], Alternative medicine, Cananga, 01 natural sciences, Liver disease, 0302 clinical medicine, Surveys and Questionnaires, HEPATOCELLULAR-CARCINOMA, Drug Discovery, Health care, Medicinal plants, 2. Zero hunger, biology, Traditional medicine, Liver Diseases, Disease Management, HEPG2 CELLS, 3. Good health, ANTIINFLAMMATORY ACTIVITIES, MEDICINAL-PLANTS, 030220 oncology & carcinogenesis, Ethnobotany, HEPATOPROTECTIVE ACTIVITY, Cambodia, medicine.medical_specialty, food.ingredient, education, SMILAX-GLABRA ROXB, PHYLLANTHUS-AMARUS, 03 medical and health sciences, food, medicine, Humans, Medicine, East Asian Traditional, Pharmacology, Plants, Medicinal, Willughbeia edulis, business.industry, ANDROGRAPHIS-PANICULATA, 15. Life on land, medicine.disease, biology.organism_classification, Diet, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Socioeconomic Factors, Ethnopharmacology, Plant Preparations, Rural area, business, GOMPHRENA-CELOSIOIDES, Phytotherapy
Abstract: International audience; Ethnopharmacological relevance: Liver disorders are a major health problem in Cambodia, where some patients prefer to seek treatment from traditional healers. The aim of the study was to document the knowledge and practices of these healers in four Southern Cambodian provinces.Materials and methods: An ethnopharmacological survey was carried out from September 2015 to January 2016 in Cambodian urban and rural areas. Thirty-three Khmer traditional healers (KTH) were interviewed using a semi-structured questionnaire including socio-demographic data, healer's formation and their professional practice conditions, perception of liver diseases (types and causes of liver disorders, diagnostic methods and symptoms of liver problems), dietary recommendations given to patients, and herbal remedies used to treat them. For each medicinal plant mentioned in herbal remedies, the local name, part of the plant, mode of preparation and administration, and their properties, according to the healers, were recorded. The plants mentioned by the traditional therapists were collected and later identified by specialists.Results: Different types of liver disease are identified by the healers, and diagnosis was mostly based on reading medical records, and by observing the yellow discoloration of the skin and eyes. A total of 42 herbal remedies including 83 medicinal plants belonging to 40 families were mentioned for treating liver disorders. The most predominant families were Leguminosae and Poaceae. Among the plants reported, Cananga latifolia, Andrographis paniculata, Smilax aff. glabra, Gomphrena celosioides, Passiflora foetida and Physalis minima were the most cited species. A large part of the herbal remedies used were multi-ingredient recipes, and were prepared mainly by a decoction administered orally. Plants are combined in multi-ingredient recipes, and selected on the basis of their properties (trocheak, psah, somrap me rok, ktchol) which originate from Khmer medical concepts. Most of the plants used by healers have a wide ethnobotanical use for liver disorders, and have been studied for their hepatoprotective activity and related activities on the liver.Conclusion: In the diagnosis and treatment of liver diseases, KTH have incorporated biomedical concepts and new practices, which suggest that they could be defined as neotraditional healers. Medicinal plants constitute the core of traditional medicine practice by these healers, and these plants play a very important role in the health care of people with liver problems in Cambodia. Therefore, more attention should be paid to the integration of healers in national health care programs for the development of combined therapies. Furthermore, two plant species (i.e. Cananga latifolia and Willughbeia edulis) were found to be widely used for treating liver disorders in our survey, and should be studied for their pharmacological potential for liver problems.
Published: 2017
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50. Development and Validation of Liquid Chromatography Combined with Tandem Mass Spectrometry Methods for the Quantitation of Simalikalactone E in Extracts of Quassia amara L. and in Mouse Blood

Author: Valérie Jullian, Eric Deharo, Mohamed Haddad, Cendrine Cabou, Marieke Vansteelandt, Hong Luyen Le, Catherine Claparols, and Nicolas Fabre
Subjects: Chromatography, biology, Chemistry, Selected reaction monitoring, Decoction, Plant Science, General Medicine, Tandem mass spectrometry, Mass spectrometry, biology.organism_classification, Biochemistry, Analytical Chemistry, Complementary and alternative medicine, Pharmacokinetics, Liquid chromatography–mass spectrometry, Drug Discovery, Molecular Medicine, Quassia amara, Ion trap, Food Science
Abstract: Introduction Simalikalactone E (SkE) from Quassia amara, has been proved to be a valuable anti-malarial and anti-cancer compound. As SkE is very scarce, methods of quantitation are needed in order to optimise its isolation process and to determine pharmacokinetic data. Objective To validate methods using liquid chromatography coupled to mass spectrometry for the quantitation of SkE in plant extracts and in biological fluids. Methods High- and ultrahigh-performance liquid chromatography (UHPLC) coupled to ion trap mass spectrometry (MS) with single ion monitoring detection and to triple quadrupole-linear ion trap tandem mass spectrometry with multiple reaction monitoring detection methods were developed. Validation procedure was realised according to the International Conference on Harmonisation guideline. Methanol extracts of dried Quassia amara leaves, and mouse-blood samples obtained after various routes of administration, were analysed for SkE. Results Methods were validated and gave similar results regarding the content of SkE expressed per kilogram of dry leaves in the traditional decoction (160 ± 12 mg/kg) and in the methanol extract (93 ± 2 mg/kg). The recovery of the analyte from mouse blood ranged from 80.7 to 119.8%. Simalikalactone E was only detected using UHPLC–MS/MS (0.2 ± 0.03 mg/L) in mouse blood after intravenous injection: none was detected following intraperitoneal or oral gavage administration of SkE. Conclusion The LC–MS methods were used for the quantitation of SkE in plant extracts and in mouse blood. These methods open the way for further protocol optimisation of SkE extraction and the determination of its pharmacokinetic data. Copyright © 2014 John Wiley & Sons, Ltd.
Published: 2014
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