Crisis de los Colegios Mayores de la Universidad de Salamanca (siglos XVIII–XX). Su vinculación con la Diputación (siglo XIX) / Crisis of the Colleges of the University of Salamanca (XVIII-XX centuries). Its link with the Diputación (XIX century)

Este trabajo constituye un relato histórico de los Colegios Mayores salmantinos. Para ello, se han revisado algunos documentos existentes en el Archivo de la Universidad de Salamanca y copias notariales de documentos inéditos custodiados por la Diputación Provincial. A pesar de que la historia de estos Colegios Mayores suele formar parte de numerosos trabajos relativos a la historia de la Universidad salmantina, el examen de dichos documentos le ha permitido al autor realizar rigurosos comentarios, que aportan originalidad en el conocimiento de este tema. (AU)

This review constitutes a historical account of the Salamanca Major Colleges. To do this, some existing documents in the Archive of the University of Salamanca and notarized copies of unpublished documents kept by the Provincial Council have been reviewed. Despite the fact that the history of these Halls of Residence is usually part of the numerous works related to the history of the University of Salamanca, the examination of these documents has allowed the author to make rigurous comments that provide originality in the knowledge of this subject. (AU)

Vinculación del virólogo profesor Adolfo García Sastre con la Universidad de Salamanca y con la Real Academia Nacional de Farmacia / Relationship of the virologist professor Adolfo García Sastre with the University of Salamanca and the Royal National Academy of Pharmacy

Se detallan y comentan algunos datos biográficos relativos al virólogo Profesor Adolfo García Sastre correspondientes a su etapa como estudiante en la Facultad de Biología de la Universidad de Salamanca, durante los cursos finales de su Licenciatura (años 1981-1986), así como a los siguientes en que realizó su Tesis de Licenciatura (Tesina) en 1986, y Doctorado (1986-1990), en el Departamento de Bioquímica y Biología Molecular de dicha Facultad (Director: Prof. J.A. Cabezas); habiendo obtenido en ambas las máximas calificaciones y el Premio Extraordinario en la de Doctorado. También se resumen las líneas de investigación que cultivó en Salamanca hasta 1991 en colaboración con el director de ambas Tesis (el Profesor Titular Enrique Villar), el Profesor J.A. Cabezas y, a veces, otros. Los resultados obtenidos, así como los derivados de su breve etapa inmediata en el Instituto Pasteur de Paris, en coordinación con el Departamento salmantino, fueron publicados en revistas de Virología o de Bioquímica de gran prestigio y presentados en congresos nacionales e internacionales. Posteriormente, en su etapa americana en el Mount Sinai de Nueva York, entró en contacto con el Profesor Mariano Esteban, entonces trabajando en el Downstate Medical Center de New York, SUNY, y ambos, conjuntamente con el grupo del New York University (NYU) dirigido por Ruth Nussenweig y Fidel Zavala, llevaron a cabo experimentos seminales de inmunología que abrieron las bases a la combinación de vacunas en protocolos prime/boost y activación de linfocitos TCD8+ con resultado de alta eficacia frente a patógenos. Estos protocolos están siendo implementados en numerosos ensayos preclínicos y clínicos. La contribución del Prof. García Sastre a la ciencia está actualmente en fase exponencial, abriendo nuevos horizontes en el entendimiento de la biología molecular de virus emergentes, su patología, interacción virus-hospedador y desarrollando nuevos procedimientos de control viral. (AU)

We give some biographical details of the virologist Professor Adolfo Garcia Sastre, as a Graduate student (1981-1986) in the Biology School of University of Salamanca and during his PhD Thesis (1986-1990) in the Department of Biochemistry and Molecular Biology (Chairman Prof J.A. Cabezas), under the supervision of Prof. Enrique Villlar and obtaining the highest academic marks. The research lines that he established in collaboration with his Thesis director, with Prof. J.A Cabezas and others, as well as his results during his stay at the Pasteur Institute in Paris, are also highlighted. His findings in this period were published in prestigious Virology and Biochemistry journals and presented at national and international meetings. Thereafter, when he moved to Mount Sinai in New York, he met Prof Mariano Esteban, then working at Downstate Medical Center in New York, SUNY, and both, in collaboration with the group of Prof. Ruth Nussenzweig and Fidel Zavala at New York University, set up seminal immunological studies that are the basis for combined vaccination approaches, prime/boost and activation of CD8+ T cells, now widely used in preclinical and clinical studies. The scientific research contributions of Prof. García Sastre are growing at an exponential rate, opening new horizons in understanding the molecular biology of emerging viruses, their pathology, virus-host cell interactions and strategies of virus control. (AU)

Colaboración hispano-alemana en Bioquímica mantenida por miembros de la Real Academia Nacional de Farmacia y por otros bioquímicos españoles / Spanish-German collaboration in Biochemistry maintained by members of the Royal Academy National of Pharmacy and by other Spanish biochemists

Considerada la Bioquímica alemana como la pionera en el mundo, ya en la etapa inicial de la misma, hacia 1872, se estableció la primera vinculación entre el Profesor alemán fundador de esta disciplina, Felix von Hoppe-Seyler, y el Catedrático español de Química Orgánica Laureano Calderón Arana. Después, algunos de los Catedráticos de la recién establecida asignatura de Química Biológica, cuya enseñanza se impartía únicamente en la Facultad de Farmacia madrileña para los alumnos de Doctorado (común a Farmacia, Medicina y Ciencias), mantuvieron esta relación, aunque menos intensa, con sus colegas germanos. Pero, a partir de 1928, el que sería Premio Nobel, Dr. Severo Ochoa, trabajó durante largos periodos en prestigiosos Departamentos de Berlín y Heidelberg. Y ya en época reciente, bioquímicos pertenecientes a la Real Academia Nacional de Farmacia (RANF) han continuado esta vinculación colaborando en diversos Departamentos alemanes. Por otro lado, bioquímicos germanos han impartido conferencias en Universidades españolas, invitados por sus colegas hispanos, además de hacerlo en congresos o simposios en España. Asimismo, algunos de ellos han sido miembros de la RANF. (AU)

German can be considered as world pioneer in the development of Biochemistry. Its founder, Prof. Felix von Hoppe-Seyler, established contacts with the Spanish Professor of Organic Chemistry, Laureano Calderón Arana, since the onset of this subject around 1872. Later, some other Professors of the newly created Química Biológica, which was taught only at the Faculty of Pharmacy in Madrid as a subject common to doctoral students in Pharmacy, Medicine and Science, maintained a connection, albeit minor, with their German colleagues. From 1928, Dr. Severo Ochoa, who would subsequently win a Nobel Prize, worked for long periods in the prestigious Departments at Berlin and Heidelberg. More recently, other biochemists, members of the Royal Academy National of Pharmacy (RANF), have followed this connection with several German Departments. Furthermore, German biochemists have delivered lectures in Spanish Universities invited by their Spanish colleagues, in addition to their participation in Spanish symposia. Moreover, several German biochemists have been RANF members. (AU)

Glicoconjugados (estructura, funciones biológicas, actividad patológica, utilización terapéutica) / Glycoconjugates (structures, biological functions, pathological activity, therapeutic use)

Se conocen principalmente algunas peculiaridades funcionales, muy importantes, de los ácidos siálicos denominados N-acetilneuramínico (NeuAc) y N-glicolilneuramínico (NeuGc), por ser agentes que participan en actividades fisiológicas o en procesos patológicos cada vez más investigados en seres humanos. Dichos ácidos forman parte de los glicoconjugados. Los glicoconjugados son moléculas resultantes de la unión fuerte, covalente, entre glúcidos y proteínas o entre glúcidos y lípidos. La desregulación de la actividad de enzimas que catalizan procesos metabólicos vinculados a los glicoconjugados produce anomalías en la estructura química de estos compuestos que impiden el desarrollo normal de la correspondiente función biológica. Tales anomalías pueden afectar a las rutas biosintéticas (desórdenes congénitos de glicosilación) o a las rutas catabólicas (anomalías por almacenamiento causadas por enzimas lisosómicas). Por fortuna, actualmente se dispone de agentes que son glicoconjugados o están relacionados con ellos que facilitan la prevención o la curación de enfermedades como la gripe, el SIDA, el cáncer, etc. Últimamente se ha intensificado la investigación con finalidad terapéutica mediante nuevos enfoques inmunológicos o genéticos relativos a los glicoconjugados, según se indica en este artículo. (AU)

Mainly N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc) exhibit very important peculiarities in certain biological (both physiological and pathological) processes. These acids are components of the glycoconjugates. Glycoconjugates are molecules resulting of the covalent link between carbohydrates and proteins or between carbohydrates and lipids. The disregulation of enzymes which catalyse the metabolic processess related to glycoconjugates produces anomalies in the chemical structure of these compounds which preclude their normal biological function, by abnormalities in the biosynthetic route (Congenital Disorders of Glycosylation) or abnormalities in the catabolic way (Lysosomal Storage Disorders). Fortunately, several agents related to glycoconjugates are now available to prevent or heal illness such as influenza, AIDS, cancer, etc. In this wiew, the research on immunological and genetic features of glycoconjugates with a therapeutic finality has been recently increased, as shown in this paper. (AU)

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation.

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr -/-). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m2), diabetes mellitus and ALT were found to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears.

Crisis de los Colegios Mayores de la Universidad de Salamanca (siglos XVIII–XX). Su vinculación con la Diputación (siglo XIX) / Crisis of the Colleges of the University of Salamanca (XVIII-XX centuries). Its link with the Diputación (XIX century)

Este trabajo constituye un relato histórico de los Colegios Mayores salmantinos. Para ello, se han revisado algunos documentos existentes en el Archivo de la Universidad de Salamanca y copias notariales de documentos inéditos custodiados por la Diputación Provincial. A pesar de que la historia de estos Colegios Mayores suele formar parte de numerosos trabajos relativos a la historia de la Universidad salmantina, el examen de dichos documentos le ha permitido al autor realizar rigurosos comentarios, que aportan originalidad en el conocimiento de este tema. (AU)

This review constitutes a historical account of the Salamanca Major Colleges. To do this, some existing documents in the Archive of the University of Salamanca and notarized copies of unpublished documents kept by the Provincial Council have been reviewed. Despite the fact that the history of these Halls of Residence is usually part of the numerous works related to the history of the University of Salamanca, the examination of these documents has allowed the author to make rigurous comments that provide originality in the knowledge of this subject. (AU)

Explanatory Factors of Burnout in a Sample of Workers with Disabilities from the Special Employment Centres (SEC) of the Amica Association, Spain.

BACKGROUND: we have based our study on the fact that the labour market is progressively becoming more accessible for people with disabilities. This investigation aims to identify the factors that contribute to high levels of work-related stress in a group of disabled individuals in order to develop policies to prevent it and promote the health of the workforce. METHODS: 131 workers from two Special Employment Centres (SECs) of the Amica Association in Cantabria (Spain) participated in the study. Sociodemographic and job-related variables were collected using a questionnaire. Work-related stress was evaluated using the Maslach Burnout Inventory General Survey (MBI-GS), which analyzes emotional exhaustion, cynicism and personal efficacy. RESULTS: the main explanatory factors for higher levels of emotional exhaustion were more than 5 years of service in the company (OR 3.235-IC 95% 1.392-7.519; p = 0.006) and bad job satisfaction (OR 7.615-IC 95% 2.467-23.503; p = 0.0001); higher levels of cynicism were also explained by bad job satisfaction (OR 8.599-IC 95% 2.481-29.799; p = 0.001). CONCLUSIONS: future research is needed to facilitate the design of company policies and promote the well-being of the disabled population in the workplace, to avoid pathological conditions such as burnout syndrome.

Vinculación del virólogo profesor Adolfo García Sastre con la Universidad de Salamanca y con la Real Academia Nacional de Farmacia / Relationship of the virologist professor Adolfo García Sastre with the University of Salamanca and the Royal National Academy of Pharmacy

Se detallan y comentan algunos datos biográficos relativos al virólogo Profesor Adolfo García Sastre correspondientes a su etapa como estudiante en la Facultad de Biología de la Universidad de Salamanca, durante los cursos finales de su Licenciatura (años 1981-1986), así como a los siguientes en que realizó su Tesis de Licenciatura (Tesina) en 1986,y Doctorado (1986-1990), en el Departamento de Bioquímica y Biología Molecular de dicha Facultad (Director: Prof.J.A. Cabezas); habiendo obtenido en ambas las máximas calificaciones y el Premio Extraordinario en la de Doctorado. También se resumen las líneas de investigación que cultivó en Salamanca hasta 1991 en colaboración con el director de ambas Tesis (el Profesor Titular Enrique Villar), el Profesor J.A. Cabezas y, a veces, otros. Los resultados obtenidos, así como los derivados de su breve etapa inmediata en el Instituto Pasteur de Paris, en coordinación con el Departamentos almantino, fueron publicados en revistas de Virología o de Bioquímica de gran prestigio y presentados en congresos nacionales e internacionales. Posteriormente, en su etapa americana en el Mount Sinai de Nueva York, entró en contacto con el Profesor Mariano Esteban, entonces trabajando en el Down state Medical Center de New York, SUNY, y ambos, conjuntamente con el grupo del New York University (NYU) dirigido por Ruth Nussenweig y Fidel Zavala, llevaron a cabo experimentos seminales de inmunología que abrieron las bases a la combinación de vacunas en protocolos prime/boosty activación de linfocitos TCD8+ con resultado de alta eficacia frente a patógenos. Estos protocolos están siendo implementados en numerosos ensayos preclínicos y clínicos. La contribución del Prof. García Sastre a la ciencia está actualmente en fase exponencial, abriendo nuevos horizontes en el entendimiento de la biología molecular de virus emergentes, su patología, interacción virus-hospedador y desarrollando nuevos procedimientos de control viral

Se detallan y comentan algunos datos biográficos relativos al virólogo Profesor Adolfo García Sastre correspondientes in the Biology School of University of Salamanca and during his PhD Thesis (1986-1990) in the Department of Biochemistry and Molecular Biology (Chairman Prof J.A. Cabezas), under the supervision of Prof. Enrique Villlar and obtaining the highest academic marks. The research lines that he established in collaboration with his Thesis director, with Prof.J.A Cabezas and others, as well as his results during his stay at the Pasteur Institute in Paris, are also highlighted. His findings in this period were published in prestigious Virology and Biochemistry journals and presented at national and international meetings. Thereafter, when he moved to Mount Sinai in New York, he met Prof Mariano Esteban, then working at Downstate Medical Center in New York, SUNY, and both, in collaboration with the group of Prof. Ruth Nus-senzweig and Fidel Zavala at New York University, set up seminal immunological studies that are the basis for combined vaccination approaches, prime/boost and activation of CD8+ T cells, now widely used in preclinical and clinical studies. The scientific research contributions of Prof. García Sastre are growing at an exponential rate, opening new horizon sin understanding the molecular biology of emerging viruses, their pathology virus-host cell interactions and strategies of virus control

Colaboración hispano-alemana en Bioquímica mantenida por miembros de la Real Academia Nacional de Farmacia y por otros bioquímicos españoles / Spanish-German collaboration in Biochemistry maintained by members of the Royal Academy National of Pharmacy and by other Spanish biochemists

Considerada la Bioquímica alemana como la pionera en el mundo, ya en la etapa inicial de la misma, hacia 1872, se estableció la primera vinculación entre el Profesor alemán fundador de esta disciplina, Felix von Hoppe-Seyler, y el Catedrático español de Química Orgánica Laureano Calderón Arana. Después, algunos de los Catedráticos de la recién establecida asignatura de Química Biológica, cuya enseñanza se impartía únicamente en la Facultad de Farmacia madrileña para los alumnos de Doctorado (común a Farmacia, Medicina y Ciencias), mantuvieron esta relación, aunque menos intensa, con sus colegas germanos. Pero, a partir de 1928, el que sería Premio Nobel, Dr. Severo Ochoa, trabajó durante largos periodos en prestigiosos Departamentos de Berlín y Heidelberg. Y ya en época reciente, bioquímicos pertenecientes a la Real Academia Nacional de Farmacia (RANF) han continuado esta vinculación colaborando en diversos Departamentos alemanes. Por otro lado, bioquímicos germanos han impartido conferencias en Universidades españolas, invitados por sus colegas hispanos, además de hacerlo en congresos o simposios en España. Asimismo, algunos de ellos han sido miembros de la RANF

German can be considered as world pioneer in the development of Biochemistry. Its founder, Prof. Felix von Hoppe-Seyler, established contacts with the Spanish Professor of Organic Chemistry, Laureano Calderón Arana, since the onset of this subject around 1872. Later, some other Professors of the newly created Química Biológica, which was taught only at the Faculty of Pharmacy in Madrid as a subject common to doctoral students in Pharmacy, Medicine and Science, maintained a connection, albeit minor, with their German colleagues. From 1928, Dr. Severo Ochoa, who would subsequently win a Nobel Prize, worked for long periods in the prestigious Departments at Berlin and Heidelberg. More recently, other biochemists, members of the Royal Academy National of Pharmacy (RANF), have followed this connection with several German Departments. Furthermore, German biochemists have delivered lectures in Spanish Universities invited by their Spanish colleagues, in addition to their participation in Spanish symposia. Moreover, several German biochemists have been RANF members

Glicoconjugados (estructura, funciones biológicas, actividad patológica, utilización terapéutica) / Glycoconjugates (structures, biological functions, pathological activity, therapeutic use)

Se conocen principalmente algunas peculiaridades funcionales, muy importantes, de los ácidos siálicos denominados N-acetilneuramínico (NeuAc) y N-glicolilneuramínico (NeuGc), por ser agentes que participan en actividades fisiológicas o en procesos patológicos cada vez más investigados en seres humanos. Dichos ácidos forman parte de los glicoconjugados. Los glicoconjugados son moléculas resultantes de la unión fuerte, covalente, entre glúcidos y proteínas o entre glúcidos y lípidos. La desregulación de la actividad de enzimas que catalizan procesos metabólicos vinculados a los glicoconjugados produce anomalías en la estructura química de estos compuestos que impiden el desarrollo normal de la correspondiente función biológica. Tales anomalías pueden afectar a las rutas biosintéticas (desórdenes congénitos de glicosilación) o a las rutas catabólicas (anomalías por almacenamiento causadas por enzimas lisosómicas). Por fortuna, actualmente se dispone de agentes que son glicoconjugados o están relacionados con ellos que facilitan la prevención o la curación de enfermedades como la gripe, el SIDA, el cáncer, etc. Últimamente se ha intensificado la investigación con finalidad terapéutica mediante nuevos enfoques inmunológicos o genéticos relativos a los glicoconjugados, según se indica en este artículo

Mainly N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc) exhibit very important peculiarities in certain biological (both physiological and pathological) processes. These acids are components of the glycoconjugates. Glycoconjugates are molecules resulting of the covalent link between carbohydrates and proteins or between carbohydrates and lipids. The disregulation of enzymes which catalyse the metabolic processess related to glycoconjugates produces anomalies in the chemical structure of these compounds which preclude their normal biological function, by abnormalities in the biosynthetic route (Congenital Disorders of Glycosylation) or abnormalities in the catabolic way (Lysosomal Storage Disorders). Fortunately, several agents related to glycoconjugates are now available to prevent or heal illness such as influenza, AIDS, cancer, etc. In this wiew, the research on immunological and genetic features of glycoconjugates with a therapeutic finality has been

Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio is linked to advanced non-alcoholic fatty liver disease lean patients.

BACKGROUND AND AIM: A small but significant proportion of patients with normal body mass index show non-alcoholic fatty liver disease (NAFLD). Oxidized low-density lipoprotein (LDL) is a powerful immunogenic molecule, which causes oxidative stress and produces antibodies (oxLDL-ab). We aimed to analyze the role of oxLDL-ab on histological features in lean-NAFLD patients. METHODS: Seventy-two biopsy-proven NAFLD patients were included. Lean patients showed body index mass of <30 kg/m(2) . Liver biopsies were assessed by one pathologist blinded to clinical data. Histological features were non-alcoholic steatohepatitis (NASH), steatosis, hepatocellular ballooning, and liver fibrosis. Metabolic and hepatic profiles were analyzed, and lipid-lowering medication was recorded. OxLDL-ab levels were measured by ELISA. OxLDL-ab-based lipid indexes analyzed: oxLDL-ab/total cholesterol ratio; oxLDL-ab/LDL-c ratio; oxLDL-ab/high-density lipoprotein cholesterol (HDL-c) ratio; and oxLDL-ab/oxLDL ratio. RESULTS: Lean-NAFLD patients presented 26.5% (9/34) of NASH. OxLDL-ab/HDL-c ratio (r = 0.570; n = 34; P = 0.001) correlated with NAS score and was the only variable associated with NASH in the multivariate analysis [odds ratio, OR, 1.10 (95% confidence interval, CI: 1.01-1.21); P = 0.039]. Severe steatosis was present in 41.2% (14/34) of lean-NAFLD patients. OxLDL-ab/HDL-c ratio was higher in patients with grade-III steatosis (54.9 (37.3-124.6)) than those with grade II (37.1 (20.2-71.1)) and grade I (17.7 (13.1-22.8)) (P = 0.018). Hepatocellular ballooning was present in 20.6% (7/34) of lean-NAFLD patients, and OxLDL-ab/HDL-c ratio (OR 1.03 [95% CI: 1.01-1.05]; P = 0.050) was independently associated with histological features. OxLDL-ab/HDL-c ratio was higher in patients with advanced fibrosis (39.8 (22.9-121.6) vs 17.7 (13.9-30.9); P = 0.025), increasing gradually with the fibrosis stage (P = 0.042) and remained in the final multivariate model [OR 1.05 (95% CI: 1.00-1.11); P = 0.05]. However, in obese-NAFLD patients, oxLDL/HDL-c ratio was not associated with histological features. CONCLUSIONS: Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio could represent an interesting biomarker associated with NASH, hepatocellular ballooning, and liver fibrosis, in lean patients. OxLDL-ab/HDL-c could play an important role for distinguishing patients with and without NAFLD complications.

Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment.

BACKGROUND: Anaemia is a common side-effect of ribavirin (RBV) use that overwhelms management of hepatitis C when protease inhibitors are added. AIM: To assess the pharmacogenomic impact of candidate genes SLC28A2, SLC28A3 and ITPA on anaemia in patients receiving triple therapy. METHODS: Patients (n=161) with chronic hepatitis C genotype 1 treated with telaprevir (n=95) or boceprevir (n=66) were included. Using RT-PCR we genotyped ITPA (rs1127354, rs7270101) and SLC28A3 (rs56350726, rs10868138) and SLC28A2 (rs11854484). Clinically significant anaemia (CSA) was diagnosed when at least one of the following criteria was observed: (a) haemoglobin <8.5g/dL during treatment; (b) blood transfusion required; (c) erythropoietin administered. RESULTS: CSA occurred in 44% (69/157) of patients and was associated with SLC28A2 rs11854484 [CC/CT genotypes: 33% (26/78) vs. TT genotype: 56% (36/64); p=0.006]. Further, the needed for blood transfusion was related to genotype [CC: 0% (0/18) vs. CT: 13% (8/61) vs. TT: 27% (17/64); p=0.016]. Similarly, ITPA rs1127354 genotypes [AA/AC: 19% (3/16) vs. CC: 45% (61/135; p=0.060] were linked to CSA. In multivariate analysis, SLC28A2 rs11854484 TT genotype (OR:2.33;95%CI:1.10-4.95; p=0.027), female sex (OR:2.54;95% CI:1.13-5.71;p=0.024) and Hb drop at week 4) OR: 1.36; 95CI%: 1.11-1.67; p=0.003) were independently associated with CSA. Similarly, ITPA rs1127354 genotypes [AA/AC: 16% (3/19) vs. CC: 63% (85/134); p=0.0001] and ITPA rs6051702 genotypes [CC/CA: 46% (26/57) vs. CC: 65% (60/93); p=0.023] were related to Hb drop of >3g/dL at week 4. CONCLUSIONS: In patients receiving first generation protease inhibitors, genotype SLC28A2 rs11854484 predicts CSA, and helps to identify a subgroup of patients with better tolerance of triple therapy.

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods.

Hepatitis C virus (HCV) is classified into seven major genotypes and 67 subtypes. Recent studies have shown that in HCV genotype 1-infected patients, response rates to regimens containing direct-acting antivirals (DAAs) are subtype dependent. Currently available genotyping methods have limited subtyping accuracy. We have evaluated the performance of a deep-sequencing-based HCV subtyping assay, developed for the 454/GS-Junior platform, in comparison with those of two commercial assays (Versant HCV genotype 2.0 and Abbott Real-time HCV Genotype II) and using direct NS5B sequencing as a gold standard (direct sequencing), in 114 clinical specimens previously tested by first-generation hybridization assay (82 genotype 1 and 32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 calling by population Sanger sequencing (69% 1b, 31% 1a) in 81 specimens and identified a mixed-subtype infection (1b/3a/1a) in one sample. Similarly, among the 32 previously indeterminate specimens, identical genotype and subtype results were obtained by direct and deep sequencing in all but four samples with dual infection. In contrast, both Versant HCV Genotype 2.0 and Abbott Real-time HCV Genotype II failed subtype 1 calling in 13 (16%) samples each and were unable to identify the HCV genotype and/or subtype in more than half of the non-genotype 1 samples. We concluded that deep sequencing is more efficient for HCV subtyping than currently available methods and allows qualitative identification of mixed infections and may be more helpful with respect to informing treatment strategies with new DAA-containing regimens across all HCV subtypes.

La investigación bioquímica en la Facultad de Farmacia de Santiago de Compostela (entre 1947 y 1981) / The biochemical investigation in the Santiago de Compostela Pharmacy Faculty (1947-1981)

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Association between vitamin D and hepatitis C virus infection: a meta-analysis.

AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and sustained virological response (SVR) in hepatitis C virus (HCV) infected individuals. METHODS: Relevant studies were identified by systematically searching MEDLINE databases up to March 2012 and abstracts of the European and American Congress of Hepatology conducted in 2011. Studies must provide information on SVR and the levels of 25(OH)D3 and/or 25(OH)D2 [henceforth referred to as 25(OH)D] in sera samples from HCV infected individuals. The inclusion criteria were: clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group; provided information on SVR rates; and were reported in the English language as full papers. Due to the heterogeneity of studies in categorizing serum vitamin D levels, a cut-off value of 30 ng/mL of serum 25(OH)D was used. Heterogeneity was assessed using I² statistics. The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model. RESULTS: Overall, 11 studies (8 observational and 3 interventional) involving 1575 individuals were included and 1117 HCV infected individuals (71%) showed low vitamin D levels. Most of the studies included mono-infected HCV individuals with the mean age ranging from 38 to 56 years. Four studies were conducted in human immunodeficiency virus/HCV infected individuals. Regarding vitamin D measurement, most of the studies employed radioimmunoassays (n = 5) followed by chemiluminescence (n = 4) and just one study employed high performance/pressure liquid chromatography (HPLC). Basal vitamin D levels varied from 17 to 43 ng/mL in the studies selected, and most of the HCV infected individuals had genotype 1 (1068/1575) with mean viral load varying from log 4.5-5.9 UI/mL. With regard to HCV treatment, most of the studies (n = 8) included HCV individuals without previous treatment, where the pooled SVR rate was 46.4%. High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL (OR = 1.57; 95%CI: 1.12-2.2) and those supplemented with vitamin D (OR = 4.59; 95%CI: 1.67-12.63) regardless of genotype. CONCLUSION: Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation.

Role of diabetes mellitus on hepatic encephalopathy.

Hepatic encephalopathy is the main cognitive dysfunction in cirrhotic patients associated with impaired prognosis. Hyperammonemia plus inflammatory response do play a crucial role on hepatic encephalopathy. However, in some patients HE appeared without hyperammonemia and patients with increased levels of ammonia could not show cognitive dysfunction. This has led to investigate other factors that could act in a synergistic way. Diabetes mellitus and insulin resistance are characterized by releasing and enhancing these pro-inflammatory cytokines and, additionally, has been related to hepatic encephalopathy. Indeed, patients with diabetes showed raised risk of over hepatic encephalopathy in comparison with non-cirrhotics. Type 2 diabetes mellitus could impair hepatic encephalopathy by different mechanisms that include: a) increasing glutaminase activity; b) impairing gut motility and promoting constipation, intestinal bacterial overgrowth and bacterial translocation. Despite of insufficient clarity about the practicability of anti-diabetic therapy and the most efficacious therapy, we would have to pay a special attention to the management of type 2 diabetes mellitus and insulin resistance in cirrhotic patients.

Origen del Departamento de Bioquímica y Biología molecular de la Universidad de Salamanca / Origin of the Department of Biochemistry and Molecular Biology of the University of Salamanca

Al crearse la Facultad de Farmacia en esta Universidad, en 1971, se constituyó oficialmente el "Departamento Interfacultativo de Bioquímica, Ciencias y Farmacia", en 1975. En la Facultad de Farmacia se impartió la enseñanza de las disciplinas de Bioquímica y Bioquímica Especial, con carácter obligatorio, y se introdujo la de la Bioquímica Clínica como optativa. Con motivo de la dotación de la Cátedra de Bioquímica en la Facultad de Farmacia en 1982, previa propuesta unánime del Profesorado bioquímico implicado, se desglosó el Departamento Interfacultativo en sendos Departamentos, que quedaron adscritos a las respectivas Facultades. Finalmente, habiéndose separado la Cátedra de Bioquímica de la Facultad de Medicina de la de Fisiología (de la que formaba parte), se constituyó en 1987 el actual Departamento, integrado por las Cátedras/Departamentos de Bioquímica procedentes de estas tres Facultades. Partiendo de cero, además de la normal tarea docente, se ha llevado a cabo una extraordinaria actividad de investigación científica, que ha merecido el reconocimiento oficial tanto nacional como internacional(AU)

Created the Chair of Biochemistry at the Faculty of Sciences of the University of Salamanca (Spain) in 1968, it was adscript as a Department to its Biological Section (soon transformed in Faculty of Biology). Structural and Metabolic Biochemistry were obligatory matters, and Molecular Biology as optative, in the studies. When the Faculty of Pharmacy was created in this University, in 1971, Biochemistry and Special Biochemistry (obligatory) and Clinical Biochemistry (as a optative) were the matters teached at the Faculty of Pharmacy by the "Interfacultative Department, Sciences and Pharmacy", constituted in 1975. In 1982, the Chair of Biochemistry was created at the Faculty of Pharmacy; and the Interfacultative Department was divided. Finally, when the Chair of Biochemistry of the Faculty of Medicine was separated from that of Phisiology, the former was integrated with those of Biology and Pharmacy to constitute, in 1987, the present Department. According to independent evaluations, the level of scientifical research carried out, from the first time, by the Chairs of this Department is very high(AU)

Metformin inhibits glutaminase activity and protects against hepatic encephalopathy.

AIM: To investigate the influence of metformin use on liver dysfunction and hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients. To analyze the impact of metformin on glutaminase activity and ammonia production in vitro. METHODS: Eighty-two cirrhotic patients with type 2 diabetes were included. Forty-one patients were classified as insulin sensitizers experienced (metformin) and 41 as controls (cirrhotic patients with type 2 diabetes mellitus without metformin treatment). Baseline analysis included: insulin, glucose, glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline HE risk was calculated according to minimal hepatic encephalopathy, oral glutamine challenge and mutations in glutaminase gene. We performed an experimental study in vitro including an enzymatic activity assay where glutaminase inhibition was measured according to different metformin concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by ammonia production at 24, 48 and 72 hours after metformina treatment. RESULTS: Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82): 4.9% (2/41) in patients receiving metformin and 41.5% (17/41) in patients without metformin treatment (logRank 9.81; p=0.002). In multivariate analysis, metformin use [H.R.11.4 (95% CI: 1.2-108.8); p=0.034], age at diagnosis [H.R.1.12 (95% CI: 1.04-1.2); p=0.002], female sex [H.R.10.4 (95% CI: 1.5-71.6); p=0.017] and HE risk [H.R.21.3 (95% CI: 2.8-163.4); p=0.003] were found independently associated with hepatic encephalopathy. In the enzymatic assay, glutaminase activity inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM) decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05). CONCLUSIONS: Metformin was found independently related to overt hepatic encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic encephalopathy. Metformin inhibits glutaminase activity in vitro. Therefore, metformin use seems to be protective against hepatic encephalopathy in diabetic cirrhotic patients.