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2. Analysis of the evolution of tuberculosis in men and women in Spain between 2017 and 2022. Is there a different incidence decline by gender?

Author

Rodrigo, Teresa, primary, Tabernero, Eva Mª, additional, Anibarro, Luis, additional, Gullón, José A, additional, Medina, Juan F, additional, Millet, Joan P, additional, García-Clemente, Marta Mª, additional, Sáez, Antonia, additional, Caylà, Joan A, additional, and García-García, José Mª, additional

Published
2024
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3. Evaluation of the Integrated Tuberculosis Research Program Sponsored by the Spanish society of pulmonology and thoracic surgery: 11 years on

Author

Agüero, R., Alcázar, J.L., Altet, N., Altube, L., Álvarez Navascués, F., Barrón, M., Bermúdez, P., Blanquer, R., Borderías, L., Bustamante, A., Calpe, J.L., Cañas, F., Casas, F., Casas, X., Cases, E., Castrodeza, R., Cebrián, J.J., Ciruelos, J.E., Delgado, A.E., Díaz, D., Fernández, B., Fernández, A., Gallardo, J., Gallego, M., García, C., García, F.J., Garros, F.J., Hidalgo, C., Iglesias, M., Jiménez, G., Kindelan, J.M., Laparra, J., Lera, R., Lloret, T., Marín, M., Martínez, J.T., Martínez, E., Martínez, A., Melero, C., Milà, C., Morales, C., Morales, M.A., Moreno, V., Muñoz, A., Muñoz, L., Muñoz, C., Muñoz, J.A., Parra, I., Pérez, J.A., Rivas, P., Rodríguez, J., Sala, J., Sánchez, M., Sánchez, P., Sanz, F., Somoza, M., Trujillo, E., Valencia, E., Vargas, A., Vidal, I., Vidal, R., Villanueva, M.A., Villar, A., Vizcaya, M., Zabaleta, M., Zubillaga, G., Rodrigo, Teresa, García-García, José-María, Caminero, José A., Ruiz-Manzano, Juan, Anibarro, Luis, García-Clemente, Marta M., Gullón, José A., Jiménez-Fuentes, M. Ángeles, Medina, Juan F., Mir, Isabel, Penas, Antón, Sánchez, Francisca, De Souza-Galvão, Maria Luiza, and Caylà, Joan A.

Published
2020
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4. Evaluación del Programa Integrado de Investigación en Tuberculosis promovido por la sociedad española de Neumología y Cirugía Torácica tras 11 años de funcionamiento

Author

Agüero, R., Alcázar, J.L., Altet, N., Altube, L., Álvarez Navascués, F., Barrón, M., Bermúdez, P., Blanquer, R., Borderías, L., Bustamante, A., Calpe, J.L., Cañas, F., Casas, F., Casas, X., Cases, E., Castrodeza, R., Cebrián, J.J., Ciruelos, J.E., Delgado, A.E., Díaz, D., Fernández, B., Fernández, A., Gallardo, J., Gallego, M., García, C., García, F.J., Garros, F.J., Hidalgo, C., Iglesias, M., Jiménez, G., Kindelan, J.M., Laparra, J., Lera, R., Lloret, T., Marín, M., Martínez, J.T., Martínez, E., Martínez, A., Melero, C., Milà, C., Morales, C., Morales, M.A., Moreno, V., Muñoz, A., Muñoz, L., Muñoz, C., Muñoz, J.A., Parra, I., Pérez, J.A., Rivas, P., Rodríguez, J., Sala, J., Sánchez, M., Sánchez, P., Sanz, F., Somoza, M., Trujillo, E., Valencia, E., Vargas, A., Vidal, I., Vidal, R., Villanueva, M.A., Villar, A., Vizcaya, M., Zabaleta, M., Zubillaga, G., Rodrigo, Teresa, García-García, José-María, Caminero, José A., Ruiz-Manzano, Juan, Anibarro, Luis, García-Clemente, Marta M., Gullón, José A., Jiménez-Fuentes, M. Ángeles, Medina, Juan F., Mir, Isabel, Penas, Antón, Sánchez, Francisca, Souza-Galvão, Maria Luiza De, and Caylà, Joan A.

Published
2020
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8. Accelerating sexual maturation of male Anastrepha ludens (Diptera: Tephritidae) fruit flies by adding two juvenile hormone analogues.

Author

Arredondo, José, Aguirre‐Medina, Juan F, Meza‐Hernández, José S, Cancino, Jorge, and Díaz‐Fleischer, Francisco

Subjects
JUVENILE hormones, ANASTREPHA, INSECT growth regulators, FRUIT flies, TEPHRITIDAE, DIPTERA, GROWTH regulators
Abstract

BACKGROUND: Improving the mating competitiveness and survival of sterile males are direct means to increase the effectiveness of the sterile insect technique (SIT). Some insecticide growth regulators, such as the juvenile hormone analogue (JHA) methoprene, have been used to improve the mating competitiveness of male tephritid flies by reducing their sexual maturation period. However, the application of methoprene reduces fly resistance to stress and decreases survival. Here, we compared the effects of methoprene and pyriproxyfen (PPF), another JHA, in Anastrepha ludens males. PPF is an insect growth regulator that exhibits higher negative effects on the larval molting process than methoprene or natural juvenile hormone. Both compounds were administered at two doses (0.05% and 0.10%) via the male diet immediately after emergence. RESULTS: Our results show that both PPF and methoprene reduced male sexual maturation. However, PPF‐treated males exhibited a shorter maturation period and obtained more matings at a given age than methoprene‐treated males. No significant differences were observed between the two PPF doses tested (0.05% and 0.10%). Male survival was equally reduced by the two compounds. CONCLUSION: Our results demonstrate that PPF accelerated sexual development without reducing the mating propensity of sterile male flies and can be used as a suitable alternative for methoprene. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Primary biliary cholangitis: pathogenic mechanisms

Author

Medicina, Medikuntza, Prieto, Jesús, Bañales Asurmendi, Jesús María, Medina, Juan F., Medicina, Medikuntza, Prieto, Jesús, Bañales Asurmendi, Jesús María, and Medina, Juan F.

Abstract

Purpose of review Primary biliary cholangitis (PBC) is characterized by autoimmune damage of intrahepatic bile ducts associated with a loss of tolerance to mitochondrial antigens. PBC etiopathogenesis is intriguing because of different perplexing features, namely: a) although mitochondria are present in all cell types and tissues, the damage is mainly restricted to biliary epithelial cells (BECs); b) despite being an autoimmune disorder, it does not respond to immunosuppressive drugs but rather to ursodeoxycholic acid, a bile salt that induces HCO3- rich choleresis; c) the overwhelming female preponderance of the disease remains unexplained. Here we present an etiopathogenic view of PBC which sheds light on these puzzling facts of the disease. Recent findings PBC develops in patients with genetic predisposition to autoimmunity in whom epigenetic mechanisms silence the Cl-/HCO3- exchanger AE2 in both cholangiocytes and lymphoid cells. Defective AE2 function can produce BECs damage as a result of decreased biliary HCO3- secretion with disruption of the protective alkaline umbrella that normally prevents the penetration of toxic apolar bile salts into cholangiocytes. AE2 dysfunction also causes increased intracellular pH (pHi) in cholangiocytes, leading to the activation of soluble adenylyl cyclase, which sensitizes BECs to bile salt-induced apoptosis. Recently, mitophagy was found to be inhibited by cytosolic alkalization and stimulated by acidification. Accordingly, we propose that AE2 deficiency may disturb mitophagy in BECs, thus, promoting the accumulation of defective mitochondria, oxidative stress and presentation of mitochondrial antigens to the immune cells. As women possess a more acidic endolysosomal milieu than men, mitophagy might be more affected in women in an AE2-defective background. Apart from affecting BECs function, AE2 downregulation in lymphocytes may also contribute to alter immunoregulation facilitating autoreactive T-cell responses. Summary PBC

Published
2021

28. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells

Author

Arenas, Fabian, Hervias, Isabel, Uriz, Miriam, Joplin, Ruth, Prieto, Jesus, and Medina, Juan F.

Subjects
Biliary cirrhosis -- Risk factors, Biliary cirrhosis -- Care and treatment, Biliary cirrhosis -- Research, Corticosteroids -- Health aspects, Corticosteroids -- Research, Ursodiol -- Health aspects, Ursodiol -- Research
Abstract

Primary biliary cirrhosis (PBC) is a cholestatic disease associated with autoimmune phenomena and alterations in both biliary bicarbonate excretion and expression of the bicarbonate carrier AE2. The bile acid ursodeoxycholic acid (UCDA) is currently used in treatment of cholestatic liver diseases and is the treatment of choice in PBC; however, a subset of PBC patients respond poorly to UDCA monotherapy. In these patients, a combination of UDCA and glucocorticoid therapy appears to be beneficial. To address the mechanism of this benefit, we analyzed the effects of UDCA and dexamethasone on AE2 gene expression in human liver cells from hepatocyte and cholangiocyte lineages. The combination of UDCA and dexamethasone, but not UDCA or dexamethasone alone, increased the expression of liver-enriched alternative mRNA isoforms AE2b1 and AE2b2 and enhanced AE2 activity. Similar effects were obtained after replacing UDCA with UDCA conjugates. In in vitro and in vivo reporter assays, we found that a UDCA/dexamethasone combination upregulated human AE2 alternate overlapping promoter sequences from which AE2b1 and AE2b2 are expressed. In chromatin immunoprecipitation assays, we demonstrated that combination UCDA/dexamethasone treatment induced p300-related interactions between HNF1 and glucocorticoid receptor on the AE2 alternate promoter. Our data provide a potential molecular explanation for the beneficial effects of the combination of UDCA and glucocorticoids in PBC patients with inadequate response to UDCA monotherapy., Introduction Ursodeoxycholic acid (UDCA) is currently being used for the treatment of cholestatic liver diseases (1-3). In contrast to classical immunosuppressors, UDCA is particularly useful in primary biliary cirrhosis (PBC), [...]

Published
2008

29. Influence of Endomycorrhizal Fungi on the Growth of Tropical Plant Species

Author

Aguirre-Medina, Juan F., Aguirre-Cadena, Juan Francisco, and Cadena-Iñiguez, Jorge

Subjects
Medical / Microbiology
Abstract

In Southeast Mexico, deforestation in tropical forests is considered an environmental concern. Deforestation favours the growth of plants that compete with species of interest, which generally present slow growth. In order to promote greater growth in less time of the forest species used in reforestation and two crops of regional interest, the effect of including Rhizophagus intraradices in the seed or the root system of seedlings were investigated to evaluate its influence on growth and allocation of dry matter in the aerial and radical part, in addition to the concentration of N, P and Ca. Also, two additional collections with morphological characteristics of Glomus sps were included in T. donnell-smithii. The results indicate that biofertilisation with R. intraradices induces increased growth and is differential in stem and root dry matter allocation over time, in addition to increasing nutrient content in plant tissue.

Published
2020

30. Acute Gastroenteritis in Children of the World: What Needs to Be Done?

Author

Guarino, Alfredo, Aguilar, Juliet, Berkley, James, Broekaert, Ilse, Vazquez-Frias, Rodrigo, Holtz, Lori, Lo Vecchio, Andrea, Meskini, Toufik, Moore, Sean, Medina, Juan F. Rivera, Sandhu, Bhupinder, Smarrazzo, Andrea, Szajewska, Hania, Treepongkaruna, Suporn, Guarino, Alfredo, Aguilar, Juliet, Berkley, James, Broekaert, Ilse, Vazquez-Frias, Rodrigo, Holtz, Lori, Lo Vecchio, Andrea, Meskini, Toufik, Moore, Sean, Medina, Juan F. Rivera, Sandhu, Bhupinder, Smarrazzo, Andrea, Szajewska, Hania, and Treepongkaruna, Suporn

Abstract

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use ofrotavirusvaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions androtavirusuniversal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included.Rotavirusimmunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.

Published
2020

33. Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice

Author

Uriarte, Iker, Fernandez-Barrena, Maite G, Monte, Maria J, Latasa, Maria U, Chang, Haisul C Y, Carotti, Simone, Vespasiani-Gentilucci, Umberto, Morini, Sergio, Vicente, Eva, Concepcion, Axel R, Medina, Juan F, Marin, José Juan G, Berasain, Carmen, Prieto, Jesus, and Avila, Matías A

Published
2013
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39. Association of ERAP2 polymorphisms in Colombian HLA-B27+ or HLA-B15+ patients with SpA and its relationship with clinical presentation: axial or peripheral predominance

Author

Londono, John, primary, Santos, Ana M, additional, Rueda, Juan C, additional, Calvo-Paramo, Enrique, additional, Burgos-Vargas, Ruben, additional, Vargas-Alarcon, Gilberto, additional, Martinez-Rodriguez, Nancy, additional, Arias-Correal, Sofia, additional, Muñoz, Guisselle-Nathalia, additional, Padilla, Diana, additional, Cuervo, Francy, additional, Reyes-Martinez, Viviana, additional, Bernal-Macías, Santiago, additional, Villota-Eraso, Catalina, additional, Avila-Portillo, Luz M, additional, Romero, Consuelo, additional, and Medina, Juan F, additional

Published
2020
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40. Evaluation of the Integrated Tuberculosis Research Program Sponsored by the Spanish society of pulmonology and thoracic surgery: 11 years on

Author

Rodrigo, Teresa, primary, García-García, José-María, additional, Caminero, José A., additional, Ruiz-Manzano, Juan, additional, Anibarro, Luis, additional, García-Clemente, Marta M., additional, Gullón, José A., additional, Jiménez-Fuentes, M. Ángeles, additional, Medina, Juan F., additional, Mir, Isabel, additional, Penas, Antón, additional, Sánchez, Francisca, additional, De Souza-Galvão, Maria Luiza, additional, Caylà, Joan A., additional, Agüero, R., additional, Alcázar, J.L., additional, Altet, N., additional, Altube, L., additional, Álvarez Navascués, F., additional, Barrón, M., additional, Bermúdez, P., additional, Blanquer, R., additional, Borderías, L., additional, Bustamante, A., additional, Calpe, J.L., additional, Cañas, F., additional, Casas, F., additional, Casas, X., additional, Cases, E., additional, Castrodeza, R., additional, Cebrián, J.J., additional, Ciruelos, J.E., additional, Delgado, A.E., additional, Díaz, D., additional, Fernández, B., additional, Fernández, A., additional, Gallardo, J., additional, Gallego, M., additional, García, C., additional, García, F.J., additional, Garros, F.J., additional, Hidalgo, C., additional, Iglesias, M., additional, Jiménez, G., additional, Kindelan, J.M., additional, Laparra, J., additional, Lera, R., additional, Lloret, T., additional, Marín, M., additional, Martínez, J.T., additional, Martínez, E., additional, Martínez, A., additional, Melero, C., additional, Milà, C., additional, Morales, C., additional, Morales, M.A., additional, Moreno, V., additional, Muñoz, A., additional, Muñoz, L., additional, Muñoz, C., additional, Muñoz, J.A., additional, Parra, I., additional, Pérez, J.A., additional, Rivas, P., additional, Rodríguez, J., additional, Sala, J., additional, Sánchez, M., additional, Sánchez, P., additional, Sanz, F., additional, Somoza, M., additional, Trujillo, E., additional, Valencia, E., additional, Vargas, A., additional, Vidal, I., additional, Vidal, R., additional, Villanueva, M.A., additional, Villar, A., additional, Vizcaya, M., additional, Zabaleta, M., additional, and Zubillaga, G., additional

Published
2020
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41. Evaluación del Programa Integrado de Investigación en Tuberculosis promovido por la sociedad española de Neumología y Cirugía Torácica tras 11 años de funcionamiento

Author

Rodrigo, Teresa, primary, García-García, José-María, additional, Caminero, José A., additional, Ruiz-Manzano, Juan, additional, Anibarro, Luis, additional, García-Clemente, Marta M., additional, Gullón, José A., additional, Jiménez-Fuentes, M. Ángeles, additional, Medina, Juan F., additional, Mir, Isabel, additional, Penas, Antón, additional, Sánchez, Francisca, additional, Souza-Galvão, Maria Luiza De, additional, Caylà, Joan A., additional, Agüero, R., additional, Alcázar, J.L., additional, Altet, N., additional, Altube, L., additional, Álvarez Navascués, F., additional, Barrón, M., additional, Bermúdez, P., additional, Blanquer, R., additional, Borderías, L., additional, Bustamante, A., additional, Calpe, J.L., additional, Cañas, F., additional, Casas, F., additional, Casas, X., additional, Cases, E., additional, Castrodeza, R., additional, Cebrián, J.J., additional, Ciruelos, J.E., additional, Delgado, A.E., additional, Díaz, D., additional, Fernández, B., additional, Fernández, A., additional, Gallardo, J., additional, Gallego, M., additional, García, C., additional, García, F.J., additional, Garros, F.J., additional, Hidalgo, C., additional, Iglesias, M., additional, Jiménez, G., additional, Kindelan, J.M., additional, Laparra, J., additional, Lera, R., additional, Lloret, T., additional, Marín, M., additional, Martínez, J.T., additional, Martínez, E., additional, Martínez, A., additional, Melero, C., additional, Milà, C., additional, Morales, C., additional, Morales, M.A., additional, Moreno, V., additional, Muñoz, A., additional, Muñoz, L., additional, Muñoz, C., additional, Muñoz, J.A., additional, Parra, I., additional, Pérez, J.A., additional, Rivas, P., additional, Rodríguez, J., additional, Sala, J., additional, Sánchez, M., additional, Sánchez, P., additional, Sanz, F., additional, Somoza, M., additional, Trujillo, E., additional, Valencia, E., additional, Vargas, A., additional, Vidal, I., additional, Vidal, R., additional, Villanueva, M.A., additional, Villar, A., additional, Vizcaya, M., additional, Zabaleta, M., additional, and Zubillaga, G., additional

Published
2020
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42. Acute Gastroenteritis in Children of the World: What Needs to Be Done?

Author

Guarino, Alfredo, primary, Aguilar, Juliet, additional, Berkley, James, additional, Broekaert, Ilse, additional, Vazquez-Frias, Rodrigo, additional, Holtz, Lori, additional, Lo Vecchio, Andrea, additional, Meskini, Toufik, additional, Moore, Sean, additional, Rivera Medina, Juan F., additional, Sandhu, Bhupinder, additional, Smarrazzo, Andrea, additional, Szajewska, Hania, additional, and Treepongkaruna, Suporn, additional

Published
2020
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45. Microencapsulation of an Extract of Sechium edule (Jacq.) Sw., with Antineoplastic Activity.

Author

Salazar-Aguilar, Sandra, Ruiz-Posadas, Lucero del Mar, Cadena-Iñiguez, Jorge, Soto-Hernández, Marcos, Santiago-Osorio, Edelmiro, Aguiñiga-Sánchez, Itzen, Cisneros-Solano, Víctor M., Aguirre-Medina, Juan F., and Olivera, Álvaro D.

Subjects
MICROENCAPSULATION, METABOLITES, DRUG administration, CONCENTRATION functions, SCANNING electron microscopy
Abstract

Microencapsulation is a technique used in pharmaceuticals as an administration vehicle. Encapsulating secondary metabolites for therapeutic purposes has been promoted recently. Microencapsulation based on chitosan was developed for the methanol extract of cv. Perla negra (S. edule (Jacq.) Sw.) (Cucurbitaceae) fruits to evaluate its viability as an administration vehicle and to assess the possible negative interaction between the extract and chitosan. Microencapsulation was performed by coacervation, implementing a method with constant sonication. The microparticles obtained were registered by means of Scanning Electron Microscopy. The presence of the bioactive in aqueous medium was recorded for release tests, measuring with spectrophotometry its concentration as a function of time. The assessment of the biological effect of the microencapsulated extract was done on the HeLa cell line and control cells (lymphocytes). Microspheres with an average size of 20 µm and a loading capacity of 98% were obtained. The highest concentration of released extract was 24 µg mL−1 at 23 h. The mainly chitosan-based microspheres did not affect the antiproliferative activity of the extract of cv. Perla negra and proved to be a potential vehicle for its therapeutic administration. The empty microspheres made with chitosan also showed to have an antiproliferative effect, and those loaded with extract showed cellular inhibition (statistical IC50) of 8 µg mL−1 without affecting the lymphocytes. Chitosan does not interfere with the biological activity of the metabolites incorporated into the microspheres since they retain their inhibitory activity on proliferation in tumor cells, thus constituting a potential vehicle for the therapeutic administration of fruit extract. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis

Author

Miszczuk, Gisel Sabrina, Banales, Jesus M., Zucchetti, Andrés E., Pisani, Gerardo Bruno, Boaglio, Andrea C., Saez, Elena, Medina, Juan F., Roma, Marcelo Gabriel, and Crocenzi, Fernando A.

Subjects
Transporter Expression, Obstructive Cholestasis, Transporter Localization, Chloride-Bicarbonate Antiporters
Abstract

In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. After 4 days of BDL, we found that neither AE2 mRNA expression (measured by quantitative real-time PCR) nor total levels of AE2 protein (assessed by western blot) were modified in freshly isolated hepatocytes. However, BDL led to a decrease in the expression of AE2 protein in plasma membrane fraction as compared with SHAM control. Additionally, AE2 activity (JOH-, mmol/L/min), measured in primary cultured hepatocytes from BDL and SHAM rats, was decreased in the BDL group versus the control group (1.9 ± 0.3 vs. 3.1 ± 0.2, p

Published
2019

47. Effect of cocoa (Theobroma cacao L.) biofertilization in nursery with Azospirillum brasilense Tarrand, Krieg et Dobereiner and Glomus intraradices Schenk et Smith/Efecto de la biofertilizacion en vivero del cacao (Theobroma cacao L) con Azospirillum brasilense Tarrand, Krieg et Dobereiner y Glomus intraradices Schenk et Smith/Efeito da biofertilizacao em viveiro de cacau (Theobroma cacao L)...

Author

Aguirre-Medina, Juan F., Mendoza-Lopez, Alexander, Cadena-Iniguez, Jorge, and Avendano-Arrazate, Carlos H.

Published
2007

49. Adaptive Downregulation of Cl-/HCO3- Exchange Activity in Rat Hepatocytes under Experimental Obstructive Cholestasis

Author

Medicina, Medikuntza, Miszczuk, Gisel S., Bañales Asurmendi, Jesús María, Zucchetti, Andrés E., Pisani, Gerardo B., Boaglio, Andrea C., Sáez, Elena, Medina, Juan F., Roma, Marcelo G., Crocenzi, Fernando A., Medicina, Medikuntza, Miszczuk, Gisel S., Bañales Asurmendi, Jesús María, Zucchetti, Andrés E., Pisani, Gerardo B., Boaglio, Andrea C., Sáez, Elena, Medina, Juan F., Roma, Marcelo G., and Crocenzi, Fernando A.

Abstract

In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. After 4 days of BDL, we found that neither AE2 mRNA expression (measured by quantitative real-time PCR) nor total levels of AE2 protein (assessed by western blot) were modified in freshly isolated hepatocytes. However, BDL led to a decrease in the expression of AE2 protein in plasma membrane fraction as compared with SHAM control. Additionally, AE2 activity (J(OH)-, mmol/L/min), measured in primary cultured hepatocytes from BDL and SHAM rats, was decreased in the BDL group versus the control group (1.9 +/- 0.3 vs. 3.1 +/- 0.2, p<0.005). cAMP-stimulated AE2 activity, however, was not different between SHAM and BDL groups (3.7 +/- 0.3 vs. 3.5 +/- 0.3), suggesting that cAMP stimulated insertion into the canalicular membrane of AE2-containing intracellular vesicles, that had remained abnormally internalized after BDL. In conclusion, our results point to the existence of a novel adaptive mechanism in cholestasis aimed to reduce biliary pressure, in which AE2 internalization in hepatocytes might result in decreased canalicular HCO3- output and decreased bile flow.

Published
2019

50. Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation of glutamic acid-296

Author

Wetterholm, Anders, Medina, Juan F., Radmark, Olof, Shapiro, Robert, Haeggstrom, Jesper Z., Vallee, Bert L., and Samuelsson, Bengt

Subjects
Leukotrienes -- Synthesis, Enzymes -- Analysis, Science and technology
Abstract

Leukotriene A4 (LTA4) hydrolase, the key enzyme in leukotriene biosynthesis, contains a zinc-binding motif with a conserved Glu-296 residue whose position indicates its involvement in the catalytic activity of the enzyme. The Glu-296 residue was substituted with glutamine and alanine residues, and the resulting mutant proteins were examined for effects on enzyme activity. The results showed that the Glu-296 residue is directly involved in the peptidase activity of the enzyme. However, this residue is not involved in the epoxide hydrolase reaction.

Published
1992

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