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Obesity and the lifestyle characteristic of our society lead young people to conditions of potential cardiovascular risk. The aim of this study was to assess the anthropometrical situation and the lifestyle in a sample of university students. A full anthropometrical evaluation was undertaken, including bioelectric impedance analysis (BIA), in 111 students in the last year of Human Nutrition and Dietetics, as well as a lifestyle questionnaire (physical activity, alcohol and cigarette consumption). A sexual dimorphism was found in weight distribution according to the classification proposed by SEEDO: 6.4% of women presented a weight lower than the health recommendations (there no men in this group) whereas 27.8% of men and 6.5% of women were in the overweight range. 15.3% of the cases had excessive waist circumference. Fat mass by BIA was higher among women. On the other hand, 67% of university students stated to perform regular physical activity, 16.7% stated being cigarette smokers, and 55.6% stated to consume high-grade alcohol. To conclude, we studied a sample population of young and healthy subjects with, however, a significant percentage of women with body weight lower than the healthy standards, overweighed people, and smokers usually taking high-grade alcohol. These data should elicit an alert of the potential cardiovascular risk in the university population if action is not taken. This population should be included in the health promotion plans. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to construct and establish the psychometric properties of the questionnaire of adherence to treatment for HIV-infected women (CAT-M VIH), contributing to the current global need of controlling HIV infection and improving the quality of life for HIV patients. The existing assessment measures are limited and deficient; hence, the development of new tools considering gender differences is important. Method: The study was instrumental (psychometric). The sample was composed of 121 women with HIV/aids attending 8 health-service facilities in the city of Cali and taking antiretroviral medication. The psychometric properties assessed were the content validity, the items discrimination ability, the factorial structure as an index to construct validity, and the reliability of the CAT-M VIH. Results: The questionnaire was finally composed of 17 items, which reflect adherence behavior to pharmacological treatment, to nonpharmacological and self-care aspects, to the prevention of sexually transmitted diseases advice, and to drug use restrictions. The preliminary psychometric properties are acceptable, having good reliability (a=0.634) and good internal structure. The items have adequate discrimination indexes and clinical relevance. Conclusions: The CAT-M VIH could aid in improving the theoretical and methodological limitations in assessing adherence to treatment of women, responding to an integral concept of such that includes more than the antiretroviral medication taken and having substantial clinical and research utility, which is discussed in this article. [ABSTRACT FROM AUTHOR]

Melanin is a substance that plays important roles in several organisms. Its function as an antioxidant and metal-complexing agent makes tyrosinase, the key enzyme that controls melanogenesis, an interesting target for designing inhibitors. In this article, we report a set of piperazine/piperidine amides of benzoic and cinnamic acid derivatives as tyrosinase inhibitors with improved potency and drug-likeness. The most potent compound 5b showed a pIC 50 of 4.99 in the monophenolase assay, and only compound 3a showed reasonable potency in the diphenolase assay (pIC 50 , 4.18). These activities are not correlated to antiradical activity, suggesting that the activity is dependent on competition with the substrates. Molecular docking studies indicated that the benzyl substituent of 5b and other analogues perform important interactions in the enzyme that may explain the higher potency of these compounds. Moreover, the compounds present adequate lipophilicity and skin permeability and no relevant cytotoxicity (CC 50 > 200 μM) to mammalian cells., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The absence of effective chronic treatment, expansion to non-endemic countries and the significant burden in public health have stimulated the search for novel therapeutic options to treat Chagas disease, a protozoan disease caused by Trypanosoma cruzi . Despite current efforts, no new drug candidates were approved in clinical trials in the past five decades. Considering this, our group has focused on the expansion of a series (LINS03) with low micromolar activity against amastigotes, considering the optimization of pharmacokinetic properties through increasing drug-likeness and solubility. In this work, we report a new set of 13 compounds with modifications in both the arylpiperazine and the aromatic region linked by an amide group. Five analogues showed activity against intracellular amastigotes (IC 50 17.8 to 35.9 µM) and no relevant cytotoxicity to mammalian cells (CC 50  > 200 µM). Principal component analysis (PCA) was performed to identify structural features associated to improved activity. The data revealed that polarity, hydrogen bonding ability and flexibility were key properties that influenced the antiparasitic activity. In silico drug-likeness assessments indicated that compounds with the 4-methoxycinammyl (especially compound 2b ) had the most prominent balance between properties and activity in the series, as confirmed by SAR analysis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The objective of this research is to study the use in the construction industry of recycled slag (SL) and fly ash (FA) using from 0.1 to 5% calcium sulfate (wCS¯). These wastes have been used to make ternary mixture systems and evaluated in terms of technological properties as cementitious materials for building applications. Studying their micro-structure as hydration products, setting times and mechanical properties shows a way to develop new mixtures from high proportion of waste, which are alternatives to the traditional nature ternary systems: Portland cement (PC), calcium aluminate cement (CAC) and calcium sulphate (CS¯). Based on previous work with natural products, the selected SL/FA ratios were 9 and 2.3 and the sulphate contents were 0, 1 and 5%. The water/binder ratio used for these cementitious mixes was 0.4. The specimens prepared for strength determination were prisms of 10 × 10 × 60 mm. The pastes were prepared and cured at 20 °C and 98% relative humidity for 1 day and then either stored at 20 °C at 98% humidity (dry) or immersed in distilled water (wet) for 14 and 28 days. The results showed that both FA and SL mixed with CS¯ produce ettringite after 28 days of setting, and this phase was the main crystalline hydrated product in all mixes. Calcium sulphate stimulates the hydration reactions of the mixes and the strength increases when the CS¯ content is higher due to ettringite formation, while the setting time decreases, as happened in the systems prepared with natural materials.

Chagas disease is an endemic tropical disease caused by the protozoan Trypanosoma cruzi , which affects around 7 million people worldwide, mostly in development countries. The treatment relies on only two available drugs, with severe adverse effects and a limited efficacy. Therefore, the search for new therapies is a legitimate need. Within this context, our group reported the anti- Trypanosoma cruzi activity of gibbilimbol B, a natural alkylphenol isolated from the plant Piper malacophyllum . Two synthetic derivatives, LINS03018 (1) and LINS03024 (2), demonstrated a higher antiparasitic potency and were selected for mechanism of action investigations. Our studies revealed no alterations in the plasma membrane potential, but a rapid alkalinization of the acidocalcisomes. Nevertheless, compound 1 exhibit a pronounced effect in the bioenergetics metabolism, with a mitochondrial impairment and consequent decrease in ATP and reactive oxygen species (ROS) levels. Compound 2 only depolarized the mitochondrial membrane potential, with no interferences in the respiratory chain. Additionally, no macrophages response of nitric oxide (NO) was observed in both compounds. Noteworthy, simple structure modifications in these derivatives induced significant differences in their lethal effects. Thus, this work reinforces the importance of the mechanism of action investigations at the early phases of drug discovery and support further developments of the series.

Previous studies reported that p-coumaric acid modulates melanoma growth. Because the esterification of p-coumaric acid (p-CA) enhanced its activity as an antimelanogenic agent, we aimed to determine the antitumor potential of two derivatives, the ethyl and butyl esters, against the murine B16-F10 and the human SK-MEL-25 melanoma cells. Cell viability was determined in vitro by the lactate dehydrogenase release and violet crystal absorption assays. The cell proliferation rate and cell cycle behavior were determined by the colony formation assay and flow cytometry analysis. Although p-CA, at the concentration of 1 mM, failed to exert a significant antitumor activity, the ethyl and butyl ester derivatives caused substantial tumor cell death at doses < 1 mM. Despite a reduction in their direct cytotoxicity at minor doses, both products controlled the melanoma growth by arresting the cell cycle at the G0/G1 (B16-F10) or S/G2 (SK-MEL-25). Furthermore, the in vivo experiments showed that the butyl ester derivative suppressed the lung B16-F10 burden, compared to the p-CA-treated mice. Thus, the esterification of p-coumaric acid improved the control over the proliferation of murine and human melanoma cells and can be considered an approach for designing novel anticancer agents.

Trypanosoma cruzi is the causing agent of Chagas disease, a parasitic infection without efficient treatment for chronic patients. Despite the efforts, no new drugs have been approved for this disease in the last 60 years. Molecular modifications based on a natural product led to the development of a series of compounds (LINS03 series) with promising antitrypanosomal activity, however previous chemometric analysis revealed a significant impact of excessive lipophilicity and low aqueous solubility on potency of amine and amide derivatives. Therefore, this work reports different modifications in the core structure to achieve adequate balance of the physicochemical properties along with biological activity. A set of 34 analogues were designed considering predicted properties related to lipophilicity/hydrosolubility and synthesized to assess their activity and selective toxicity towards the parasite. Results showed that this strategy contributed to improve the drug-likeness of the series while considerable impacts on potency were observed. The rational analysis of the obtained data led to the identification of seven active piperazine amides (28-34, IC 50 8.7 to 35.3 µM against intracellular amastigotes), devoid of significant cytotoxicity to mammalian cells. The addition of water-solubilizing groups and privileged substructures such as piperazines improved the physicochemical properties and overall drug-likeness of these compounds, increased potency and maintained selectivity towards the parasite. The obtained results brought important structure-activity relationship (SAR) data and new lead structures for further modifications were identified to achieve improved antitrypanosoma compounds., (Copyright © 2022. Published by Elsevier B.V.)

Considering the emergence of antifungal resistance on Sporothrix brasiliensis, we aimed to assess new benzylidene-carbonyl compounds against feline-borne S. brasiliensis isolates. The compounds were designed as bioisosteres from previously reported benzylidene-ketones generating the p-coumaric (1), cinnamic (2), p-methoxycinnamic (3) and caffeic acid (4) analogues. The corresponding compounds were tested against feline isolates of S. brasiliensis with sensitivity (n = 4) and resistance (n = 5) to itraconazole (ITZ), following the M38-A2 protocol (CLSI, Reference method for broth dilution antifungal susceptibility testing of filamentous fungi M38-A2 Guideline, 2008). Eleven analogues showed activity against all fungal strains with minimum inhibitory concentrations (MIC) ≤1 mg/ml (1a-d, 2e, 3b, 3e, 4, 4a and 5e) and fungicidal concentrations (MFC) ≤1 mg/ml (1b, 1d, 3e and 4a), whereas 3 was the less active with both MIC and MFC values above 1 mg/ml. Compound 3e (4-methoxy-N-butylcinnamamide) was the most potent (MIC range 0.08-0.16 mg/ml; MFC range 0.32-0.64 mg/ml) from the set, suggesting a different role of the substituents in ester and amide derivatives. The designed compounds proved to be important prototypes with improved drug-likeness to achieve compounds with higher activity against ITZ-resistant S. brasiliensis., (© 2021 John Wiley & Sons A/S.)

Histamine acts through four different receptors (H 1 R-H 4 R), the H 3 R and H 4 R being the most explored in the last years as drug targets. The H 3 R is a potential target to treat narcolepsy, Parkinson's disease, epilepsy, schizophrenia and several other CNS-related conditions, while H 4 R blockade leads to anti-inflammatory and immunomodulatory effects. Our group has been exploring the dihydrobenzofuranyl-piperazines (LINS01 series) as human H 3 R/H 4 R ligands as potential drug candidates. In the present study, a set of 12 compounds were synthesized from adequate (dihydro)benzofuran synthons through simple reactions with corresponding piperazines, giving moderate to high yields. Four compounds (1b, 1f, 1g and 1h) showed high hH 3 R affinity (pK i  > 7), compound 1h being the most potent (pK i 8.4), and compound 1f showed the best efficiency (pKi 8.2, LE 0.53, LLE 5.85). BRET-based assays monitoring Gα i activity indicated that the compounds are potent antagonists. Only one compound (2c, pK i 7.1) presented high affinity for hH 4 R. In contrast to what was observed for hH 3 R, it showed partial agonist activity. Docking experiments indicated that bulky substituents occupy a hydrophobic pocket in hH 3 R, while the N-allyl group forms favorable interactions with hydrophobic residues in the TM2, 3 and 7, increasing the selectivity towards hH 3 R. Additionally, the importance of the indole NH in the interaction with Glu5.46 from hH 4 R was confirmed by the modeling results, explaining the affinity and agonistic activity of compound 2c. The data reported in this work represent important findings for the rational design of future compounds for hH 3 R and hH 4 R., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We evaluated the antifungal activity of benzylidene-carbonyl compounds (LINS03) based on the structure of gibbilimbol from Piper malacophyllum Linn. Five analogues (1-5) were synthetized following a classic aldol condensation between an aromatic aldehyde and a ketone, under basic conditions. These were tested against itraconazole-susceptible (n = 3) and itraconazole-resistant (n = 5) isolates of Sporothrix brasiliensis by M38-A2 guidelines of CLSI. All of them were fungistatic (MIC ranged of 0.11-0.22 mg/mL (1); 0.08-0.17 mg/mL (2); 0.05-0.1 mg/mL (3); 0.04-0.33 mg/mL (4); and 0.04-0.3 mg/mL (5)), highlighting compounds 2 and 3. As fungicidal, compounds 1 and 2 were highlighted (MFC ranged of 0.22-0.89 mg/mL and 0.08-1.35 mg/mL, respectively), compared with the remaining (0.77-> 3.08 mg/mL (3); 0.08-> 2.6 mg/mL (4); and 0.59-> 2.37 mg/mL (5)). The inhibitory activity was related to the benzylidene-carbonyl, whereas the phenol group and the low chain homolog seems to contribute to some extent to the fungicidal effect. Compound 2 highlighted due to the considerable fungistatic and fungicidal activities, including itraconazole-resistant Sporothrix brasiliensis. These findings support the potential usefulness of benzylidene-carbonyl compounds as promising prototypes for the development of antifungal against sporotrichosis by Sporothrix brasiliensis, including against itraconazole-resistant isolates.

Cement based materials may contain varying levels of radionuclides, mainly 226 Ra (from the 238 U series), 232 Th and 40 K, which are used to determine the Activity Concentration Index ("ACI"). According to the European directive Euratom 2013/59 in these materials, the "ACI" must be < 1 to be suitable for their use in construction. In this paper, data on the activity concentration of natural radionuclides in cement-based materials (i.e. cements, additions, pigments and aggregates) as well as their chemical composition are presented. Radioactivity measurements have been determined by using gamma spectroscopy the chemical compositions have been determined by X-Ray Fluorescence. Data for cements measured shown that white cements present a lower concentration of activity than conventional CEM I. In addition, the CAC (Calcium aluminate cements) present high activity concentration in the 232 Th series. Regarding additions, FA (Fly Ash) are those that present the highest concentration of activity in the 238 U and 232 Th series, while olive biomass ashes are those supplementary cementitious materials that show the highest concentration of activity for 40 K. Some pigments used in mortar and concrete technology were also characterized. Granitic and volcanic rocks, potentially used as aggregates present much higher activity concentration than the siliceous aggregate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Authors. Published by Elsevier Inc.)

Fungal infections are on the rise, since the imunocompromised population is increasing due to AIDS/HIV, organ transplant and chemotherapy. Many environmental and pathogenic fungi are able to accomplish melanin biosynthesis as a virulence factor to promote host invasion. Melanized cells are more resistant to radiation, oxidative and osmotic stresses; also melanin confers an advantage in vivo, since melanized cells are more resistant to phagocytic engulfment and oxidative stress caused by the host defense cells and by some antifungal drugs, such as fluconazole (FCZ) and amphotericin B (AmB). Brown, red or black melanin pigments can be produced by the polyketide pathway (DHN-melanin) or from dihydroxyphenols, such as L-DOPA (L-3,4-dihydroxyphenylalanine) and L-tyrosine by polyphenoloxidases. Among several pathogenic fungi, Cryptococcus neoformans is a melanized yeast that causes pneumonia and meningoencephalitis in immunocompromised patients. The knockout of the laccase genes or other interruptions on melanin biosynthetic pathway generates cryptococcal strains with attenuated virulence in an animal model. In this study 16 analogues of coumaric and cinnamic acid were evaluated as possible tyrosinase inhibitors. We have identified some valuable inhibitors of C. neoformans growth and melanin biosynthesis disruption agents. The results showed that coumaric acid derivatives (1a-c), the ketones (3a-b) and 2-allylphenol (7c) are significant inhibitors of tyrosinase and melanization of the fungus. Two analogues (1b and 3b) were selected as promising antimelanogenic agents to be combined with AmB, showing to promote 16-fold reduction in the AmB fungicidal concentration with no appreciable cytotoxicity to mammalian cells. The data suggest that inhibition of the melanin biosynthesis by these compounds may increase the susceptibility of the cells to the oxidative stress generated by AmB. In summary, our data show that C. neoformans can be a suitable model system to test novel inhibitors that target melanin biosynthesis, and novel compounds for adjunct therapy against C. neoformans were identified., Competing Interests: Declarations of Competing Interest The authors declare no competing interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

p-Coumaric acid is a known inhibitor of tyrosinase, an enzyme involved in the initial steps of the melanin synthesis in human and other species. However, its low lipophilicity impairs its penetration through skin and efficacy as antimelanogenic agent indeed. Accordingly, this paper reports the assessment of several coumaric acid derivatives as tyrosinase inhibitors and antimelanogenic agents in in vitro, in silico and ex vivo assays. The compounds were designed with modifications in the aromatic and acid moieties of p-coumaric acid, being the coumarate esters the most promising derivatives. The compounds showed higher tyrosinase inhibitory activity (pIC 50 3.7-4.2) than the parent acid, being compounds 1d, 1e and 1f the most potent inhibitors. Docking analysis showed that these esters are competitive inhibitors per se, and act independently of a redox mechanism as suggested by DPPH assays. Moreover, the esters showed efficacy in reducing the melanin deposition in human skin fragments at 0.1% concentration, especially compound 1e. In summary, there is an important equilibria between tyrosinase affinity and lipophilicity that must be considered to get effective antimelanogenic agents with adequate permeability in the skin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neolignan licarin A (1) was isolated from leaves of Nectandra oppositifolia (Lauraceae) and displayed activity against trypomastigote forms of the etiologic agent of American trypanosomiasis, Trypanosoma cruzi. Aiming for the establishment of SAR, five different compounds (1a - 1e) were prepared and tested against T. cruzi. The 2-allyl derivative of licarin A (1d) exhibited higher activity against trypomastigotes of T. cruzi (IC 50  = 5.0 μM and SI = 9.0), while its heterocyclic derivative 1e displayed IC 50 of 10.5 μM and reduced toxicity against NCTC cells (SI > 19.0). However, these compounds presented limited oral bioavailability estimation (<85%, Papp <1.0 × 10 -6  cm/s) in parallel artificial membrane permeability assays (PAMPA) due to excessive lipophilicity. Based on these results, different simplified structures of licarin A were designed: vanillin (2), vanillyl alcohol (3), isoeugenol (4), and eugenol (5), as well as its corresponding methyl (a), acetyl (b), O-allyl (c), and C-allyl (d) analogues. Vanillin (2) and its acetyl derivative (2b) displayed expressive activity against intracellular amastigotes of T. cruzi with IC 50 values of 5.5 and 5.6 μM, respectively, and reduced toxicity against NCTC cells (CC 50  > 200 μM). In addition, these simplified analogues showed a better permeability profile (Papp > 1.0 × 10 -6  cm/s) on PAMPA models, resulting in improved drug-likeness. Vanillyl alcohol acetyl derivative (3b) and isoeugenol methyl derivative (4a) displayed activity against the extracellular forms of T. cruzi (trypomastigotes) with IC 50 values of 5.1 and 8.8 μM respectively. Based on these results, compounds with higher selectivity index against extracellular forms of the parasite (1d, 1e, 3d, and 4a) were selected for a mechanism of action study. After a short incubation period (1 h) all compounds increased the reactive oxygen species (ROS) levels of trypomastigotes, suggesting cellular oxidative stress. The ATP levels were increased after two hours of incubation, possibly involving a high energy expenditure of the parasite to control the homeostasis. Except for compound 4a, all compounds induced hyperpolarization of mitochondrial membrane potential, demonstrating a mitochondrial imbalance. Considering the unique mitochondria apparatus of T. cruzi and the lethal alterations induced by structurally based on licarin A, these compounds are interesting hits for future drug discovery studies in Chagas disease.

Background: Neglected tropical diseases are a group of infections caused by microorganisms and viruses that affect mainly poor regions of the world. In addition, most available drugs are associated with long periods of treatment and high toxicity which limits the application and patient compliance. Investment in research and development is not seen as an attractive deal by the pharmaceutical industry since the final product must ideally be cheap, not returning the amount invested. Natural products have always been an important source for bioactive compounds and are advantageous over synthetic compounds when considering the unique structural variety and biological activities. On the other hand, isolation difficulties and low yields, environmental impact and high cost usually limit their application as drug per se., Objective: In this review, the use of natural products as prototypes for the semi-synthesis or total synthesis, as well as natural products as promising hits is covered, specifically regarding compounds with activities against trypanosomatids such as Trypanosoma spp. and Leishmania spp., Methods: Selected reports from literature with this approach were retrieved., Conclusion: As summary, it can be concluded that natural products are an underestimated source for designing novel agents against these parasites., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Verifying the compliance with the ethical principles of health research legitimizes its exercise in the eyes of the society and allows for the resolution of ethical dilemmas that emerge from new research interests and methods. Resolution 8430 of 1993 is one of the main ethical guidelines governing health research on human beings in Colombia. Considering that the resolution has not been revised or updated since its promulgation it becomes necessary to evaluate its current validity and adequacy to address the potential ethical dilemmas in the existing country’s health research. Some gaps, contradictions, and aspects that require a deep review are detailed in this paper from a wide conception of health research areas and methods. After discussing the main weaknesses and inaccuracies, some alternatives are proposed to adjust the resolution to the present needs in health research with human beings.

Chagas' disease is a parasitic infection caused by Trypanosoma cruzi that is still treated by old and toxic drugs. In the search for novel alternatives, natural sources are an important source for new drug prototypes against T. cruzi to further structural exploitation. A set of natural-based compounds (LINS03) was designed, showing promising antitrypanosoma activity and low cytotoxicity to host cells. In this paper, nine novel LINS03 derivatives were evaluated against T. cruzi trypomastigotes and amastigotes. The selectivity was assessed through cytotoxicity assays using NCTC mammalian cells and calculating the CC 50 /IC 50 ratio. The results showed that compounds 2d and 4c are noteworthy, due their high activity against amastigotes (IC 50 13.9 and 5.8 µM) and low cytotoxicity (CC 50 107.7 µM and >200 µM, respectively). These compounds did not showed alteration on plasma membrane permeability in a Sytox green model. SAR analysis suggested an ideal balance between hydrosolubility and lipophilicity is necessary to improve the activity, and that insertion of a meta-substituent is detrimental to the activity of the amine derivatives but not to the neutral derivatives, suggesting different mechanisms of actions. The results presented herein are valuable for designing novel compounds with improved activity and selectivity to be applied in future studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The γ-radiation emitted by building materials is calculated from the activity indices for 232 Th, 226 Ra and 40 K and expressed as the activity concentration index (ACI). Gamma spectroscopy is a non-destructive technique frequently used to simultaneously determine the indices for several radionuclides. Spectral interpretation poses a number of challenges, including identification of γ-lines subject to summing-in effects, interference from other γ-ray emitting radionuclides and the time required to reach secular equilibrium. These challenges are not fully addressed by Canberra Industries' Genie 2000, the software used by many laboratories to analyse samples. This article describes a Microsoft Excel workbook that exploits Genie 2000 flexibility to program applications with Visual Basic using Canberra's Nuclear Data Access Library and batch procedure tools. The workbook determines 40 K activity concentration after correcting for 228 Ac interference and 226 Ra activity directly from the γ-peak at 186.5 keV. The method proposed was tested by participating in 13 national and international scale inter-comparison exercises. The results were statistically indistinguishable from the reference values at a coverage factor of k = 3 and no statistically significant differences were identified between the respective means by a Student's t pairwise comparison., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This work reports a repurposing study of pyrazinoic acid (1) and methyl (2), ethyl (3) and 2-chloroethyl (4) ester derivatives with antimycobacterial activity, in assays against Trypanosoma cruzi. The compounds and benznidazole, the standard antitrypanosoma drug, were evaluated in concentrations ranging from 100 to 6.25 μg/mL. The results showed that compounds 2 and 3 (EC 50  = 182 and 447 μM) significantly reduced the infection rate of the parasite into the mammalian cells at 100 μg/mL (p < 0.05) in a similar way to benznidazole. In addition, all the compounds also significantly reduced the number of intracellular parasites (compound 1 at 50 μg/mL, and compounds 2-4 at 100 μg/mL, p < 0.05) in comparison to the control. Compounds 1 and 2 were more effective than benznidazole at 50 μg/mL (p < 0.001). Moreover, compounds 1-4 did not show significant cytotoxicity against THP-1, J774, and HeLa cells (>1000 μM), indicating that they possess considerable selectivity against the parasites. This report represents the first study of such compounds against T. cruzi, indicating the potential of pyrazinoates as antiparasitic agents., (© 2018 Deutsche Pharmazeutische Gesellschaft.)

Chagas' disease and leishmaniasis are parasitic infections enrolled among the neglected tropical diseases, which urge for new treatments. In the search for new chemical entities as prototypes, gibbilimbols A/B have shown antiparasitic activity against Trypanosoma cruzi and Leishmania infantum, and then a set of analogues (LINS03 series) of this natural product were synthesized and evaluated in vitro against the parasites. In the present paper we reported five new compounds with activity against these protozoan parasites, and quite low cytotoxicity. Moreover, the interference of plasma membrane permeability of these analogues were also evaluated. We found that [(4-methoxyphenyl)methyl]octylamine (4) was noteworthy due to its high activity against the amastigote form of both parasites (IC 50 1.3-5.8 μM) and good selectivity index. In order to unveil the SAR for this chemotype, we also presented a group efficiency analysis and PCA and HCA study, which indicated that the methoxyl provides good activity with lower cytotoxicity to mammalian cells. The results from SAR analyses suggest different mechanisms of action between the neutral and basic compounds. In summary, the analogues represent important activity against these parasites and must be prototypes for further exploitation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 μM against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI=13.1) and T. cruzi (SI=4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The purpose of this study was to assess the prevalence of, and the factors associated with HIV testing and pre- and post-test counselling (PPTC) in Colombia. Cross-sectional data from the National Health Survey carried out during 2007 were analysed. Data were gathered from records of 29,760 individuals between the ages of 18 and 69 from the main regions of the country. Only 19.7% of the sample had taken an HIV test. Men, people with no education, those not affiliated with the health-care system, residents of rural areas and those aged older than 65 were less likely to have been tested for HIV; 42% of those tested did not receive pre-test counselling and 56.9% received no report of the results. Considering the low prevalence of HIV testing among the Colombian population, it is necessary to design and apply guidelines for HIV screening in all health-care settings and to conduct targeted testing in high-risk sub-populations. A national norm of PPTC in those who undergo HIV testing should be examined.

This paper describes an industrial process for stabilising sewage sludge (SS) with lime and evaluates the viability of the stabilised product, denominated Neutral, as a raw material for the cement industry. Lime not only stabilised the sludge, raised the temperature of the mix to 80-100°C, furthering water evaporation, portlandite formation and the partial oxidation of the organic matter present in the sludge. Process mass and energy balances were determined. Neutral, a white powder consisting of portlandite (49.8%), calcite (16.6%), inorganic oxides (13.4%) and organic matter and moisture (20.2%), proved to be technologically apt for inclusion as a component in cement raw mixes. In this study, it was used instead of limestone in raw mixes clinkerised at 1400, 1450 and 1500°C. These raw meals exhibited greater reactivity at high temperatures than the limestone product and their calcination at 1500°C yielded clinker containing over 75% calcium silicates, the key phases in Portland clinker. Finally, the two types of raw meal (Neutral and limestone) were observed to exhibit similar mineralogy and crystal size and distribution., (Published by Elsevier Ltd.)

Objective: To assess the usefulness of the Practidose individualised dispensing and dosing pillbox system in improving treatment compliance (TC)., Design: Open-labelled, randomised, clinical trial., Setting: Cordoba province from April to September 2005., Participants and Context: A total of 220 patients 70 years diagnosed with ineffective management of treatment regime, polymedicated with no cognitive deterioration or limited mobility. Enrolment was carried out by block random assignment. Each district linking nurse was assigned 10 interviews, 5 from the intervention group and 5 from a control group., Intervention: To give a smart pillbox with instructions. MEASUREMENTS AND PRIMARY OUTCOMES: The response variable was the TC measured using the Morisky-Green questionnaire at the beginning and at 2 months. The independent variables were: age, sex, education level, number of people living in the home and mean age, diabetes, hypertension, heart disease, COPD, number of medications, number of daily and weekly doses self-medication, and interest in the patient information leaflet. A descriptive analysis and a multiple logistic regression were performed on the data. A total of 182 patients finished the study. The TC improved by 6.74% in the intervention group and by 2.15% in the control group. To look after the medications and suffer from COPD lead to better TC, and was less so when there was interest in the patient information leaflet., Conclusions: The improvement in treatment compliance with the Practidose Pillbox was not statistically significant, although a positive tendency was observed.

The amygdaloid complex is a group of nuclei located deep in the temporal lobe and closely involved in the limbic system. Its alteration has been associated with some psychiatric processes. In this article, an overall review was made of the published data concerning the amygdaloid complex in the most common psychiatric diseases. A damaged amygdaloid complex is commonly observed, that in the Klüver-Bucy syndrome presents the fullest expression. A decrease in the amygdaloid complex of schizophrenic patients has been observed. This finding was found bilaterally in men whereas in women it was only located in one hemisphere. This finding suggests that morphometric alterations in the amygdaloid complex are more diffuse and more severe in men with schizophrenia. This subcortical complex is larger in children with autism, but not in adolescents, in whom the amygdaloid complex volume matches the normal volume of an adolescent or an adult without this pathology. However, neuroanatomical studies have shown microscopic alterations. In patients with mood disorders, it has been reported that the left amygdaloid complex presents a lesser volume. Moreover, in frontotemporal dementia and Alzheimer disease a slight amygdaloid atrophia was found related to the healthy controls. It can be concluded that the amygdaloid complex is involved in several psychiatric processes, due to structural or functional damage. However, more studies are still needed in order to delimitate the real influence of the amygdaloid complex in these disorders.

Objectives: To ascertain and analyse the drug consumption of the immobile elderly, as well as the number of potentially inappropriate medications (PIM)., Design: Cross-sectional study., Setting: Fourteen rural primary care centres., Participants: Non-institutionalised immobile patients, older than 64 years were selected by systematic sampling., Principal Measurements: Review of patients' medicine cabinets and noting the daily doses and current number of drugs, as well as the origin of the prescription. Identification of PIM (Beers criteria)., Results: One-hundred forty-three homes visits were made. The mean age was 81.3+/-7.9 years, of whom 74.8% were women. The most common drugs were: analgesics (9.2%), antacids (7.1%), nitrites-calcium antagonists (6.5%), non-steroidal anti-inflammatories (5.0%), and angiotensin converting enzyme inhibitors (4.7%). The percentage of patients who took more than 4 drugs was 76.1%. A PIM was taken by 35% of the elderly. The most common were: long-acting tranquilisers (41.5%), hypnotics (13.8%), digoxin (13.8%), indomethacin (7.7%), and antispasmodics (6.1%). In the majority of cases, the prescribing of the PIM was made by the family doctor (77.7%). Women took significantly more inappropriate drugs than men (0.50+/-0.72 vs to 0.25+/-0.50; P=.001) and those on multiple medication more than those not on multiple medication (0.50+/-0.73 vs 0.31+/-0.52; P=.008)., Conclusions: The prevalence of inappropriate therapy in the immobile elderly is high, therefore an effort must be made to reduce it. Procedures directed towards increasing the quality of prescribing could improve the state of health and quality of life of these patients.