Investigaciones científico-pesqueras en las aguas del Océano Pacífico adyacentes a la costa del Perú durante el invierno de 1972. Expedición del BEC Profesor Mesyatsev en los meses de agosto-setiembre de 1972

Brinda información acerca del relieve del fondo, condiciones hidrológicas, dinámica de las aguas correspondientes a la parte norte de la corriente peruana durante el invierno y características hidroquímicas de las aguas frente a la costa del Perú durante el invierno de 1972.

Tercer crucero del barco de exploración científica Profesor Mesiatsev (VNIRO) 24 de octubre - 6 de diciembre 1972. Investigaciones científico-pesqueras en las aguas del Océano Pacífico aledañas a la costa del Perú durante la primavera de 1972

Da a conocer las condiciones hidrológicas, características hidroquímicas, distribución del estado biológico de los peces frente a la costa y estudia las corrientes en las aguas peruanas durante la primavera de 1972.

Riesgo Ergonómico en Estudiantes de Odontología de la Universidad de Antioquia, Colombia

Antecedentes y objetivo: El ejercicio de la práctica odontológica supone factores de riesgo para desarrollar desórdenes musculoesqueléticos, tales como movimientos repetitivos con las manos, fuerza aplicada durante los movimientos, posiciones incomodas prolongadas, presencia de vibración, entre otros. El objetivo de este trabajo fue determinar la prevalencia de exposición a los riesgos ergonómicos, así como problemas de salud asociados, en estudiantes de odontología de la Universidad de Antioquia (Colombia).

Investigaciones biológico pesqueras en la región Tumbes, Perú. 1996 – 2005

analiza las características oceanográficas del mar de la región Tumbes en relación con el resto del mar peruano.

Monitoreo de invertebrados marinos en estaciones fijas del Callao, 2008-2012

Se presentan resultados de investigaciones sobre reclutamiento, estructura por tallas y abundancia de Stramonita chocolata, Argopecten purpuratus, Cancer setosus (= Romaleon polyodon) y Glycymeris ovata efectuados en los bancos naturales de Callao durante el 2008-2012, así como del experimento de marcación - recaptura de A. purpuratus en la bahía del Callao el 2011-2012. Con los resultados del monitoreo de invertebrados marinos en estaciones fijas del 2008 al 2012 se establecieron patrones temporales y espaciales del reclutamiento y abundancia que tendrían fuerte impacto en la determinación de medidas alternativas de manejo en la regulación pesquera. Con los resultados de marcación – recaptura de A. purpuratus se determinaron parámetros de crecimiento von Bertalanffy: 100 mm para longitud infinita, 0,891 y 0,931 año-1 para k para los años 2011 y 2012 respectivamente, y -0.04 para t0. También se presentan resultados del monitoreo de Octopus mimus en las islas de la región Lima (Ancón- Asia) los cuales muestran por primera vez índices de abundancia, distribución y aspectos biológicos.

Anuario Científico y Tecnológico IMARPE 2012

Reúne información sobre los Programas de investigación y actividades/proyectos realizados por las Direcciones de Investigación de la Sede Central y las diez Sedes Descentralizadas del IMARPE. Se destacan los resultados logrados en base a la Matriz de Actividades y Proyectos de Investigaciones Científicas y Tecnológicas durante el año 2012.

Leishmania RNA virus: when the host pays the toll.

The presence of an RNA virus in a South American subgenus of the Leishmania parasite, L. (Viannia), was detected several decades ago but its role in leishmanial virulence and metastasis was only recently described. In Leishmania guyanensis, the nucleic acid of Leishmania RNA virus (LRV1) acts as a potent innate immunogen, eliciting a hyper-inflammatory immune response through toll-like receptor 3 (TLR3). The resultant inflammatory cascade has been shown to increase disease severity, parasite persistence, and perhaps even resistance to anti-leishmanial drugs. Curiously, LRVs were found mostly in clinical isolates prone to infectious metastasis in both their human source and experimental animal model, suggesting an association between the viral hyperpathogen and metastatic complications such as mucocutaneous leishmaniasis (MCL). MCL presents as chronic secondary lesions in the mucosa of the mouth and nose, debilitatingly inflamed and notoriously refractory to treatment. Immunologically, this outcome has many of the same hallmarks associated with the reaction to LRV: production of type 1 interferons, bias toward a chronic Th1 inflammatory state and an impaired ability of host cells to eliminate parasites through oxidative stress. More intriguing, is that the risk of developing MCL is found almost exclusively in infections of the L. (Viannia) subtype, further indication that leishmanial metastasis is caused, at least in part, by a parasitic component. LRV present in this subgenus may contribute to the destructive inflammation of metastatic disease either by acting in concert with other intrinsic "metastatic factors" or by independently preying on host TLR3 hypersensitivity. Because LRV amplifies parasite virulence, its presence may provide a unique target for diagnostic and clinical intervention of metastatic leishmaniasis. Taking examples from other members of the Totiviridae virus family, this paper reviews the benefits and costs of endosymbiosis, specifically for the maintenance of LRV infection in Leishmania parasites, which is often at the expense of its human host.

En el corazón de las tinieblas... del Putumayo, 1890-1932. Fronteras, caucho, mano de obra indígena y misiones católicas en la nacionalización de la Amazonía

Objetivo del artículo es reflexionar sobre el llamado «escándalo del Putumayo» estallado en la primera década del siglo XX, en la región objeto de litigio fronterizo entre Perú y Colombia. La denuncia en la prensa internacional de la explotación de los indígenas amazónicos hecha por la empresa «Peruvian Amazon Company», de la que el principal accionista fue el cauchero Julio C. Arana, presentó la región como un nuevo «Congo peruano» y provocó la intervención de Gran Bretaña, Perú, el Vaticano, Colombia y el propio Arana. A partir de repositorios documentales de la cancillería peruana, de los archivos de la Santa Sede, de la folletística y bibliografía publicada por las partes involucradas se plantea una reflexión sobre el escándalo, incidiendo en los argumentos sostenidos por las partes, en particular la peruanización de la región, defendida por Arana y el gobierno peruano.

Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection.

Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies.

Hepatitis B Virus e Antigen Physically Associates With Receptor-Interacting Serine/Threonine Protein Kinase 2 and Regulates IL-6 Gene Expression.

We previously reported that hepatitis B virus (HBV) e antigen (HBeAg) inhibits production of interleukin 6 by suppressing NF-κB activation. NF-κB is known to be activated through receptor-interacting serine/threonine protein kinase 2 (RIPK2), and we examined the mechanisms of interleukin 6 regulation by HBeAg. HBeAg inhibits RIPK2 expression and interacts with RIPK2, which may represent 2 mechanisms through which HBeAg blocks nucleotide-binding oligomerization domain-containing protein 1 ligand-induced NF-κB activation in HepG2 cells. Our findings identified novel molecular mechanisms whereby HBeAg modulates intracellular signaling pathways by targeting RIPK2, supporting the concept that HBeAg could impair both innate and adaptive immune responses to promote chronic HBV infection.

Identification of GPx8 as a novel cellular substrate of the hepatitis C virus NS3-4A protease

Background: The hepatitis C virus (HCV) NS3-4A protease is not only an essential component of the viral replication complex and a prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. It cleaves and thereby inactivates two crucial adaptor proteins in viral RNA sensing and innate immunity (MAVS and TRIF) as well as a phosphatase involved in growth factor signaling (TC-PTP). The aim of this study was to identify novel cellular substrates of the NS3-4A protease and to investigate their role in the life cycle and pathogenesis of HCV. Methods: Cell lines inducibly expressing the NS3-4A protease were analyzed in basal as well as interferon- α -stimulated states by stable isotopic labeling using amino acids in cell culture (SILAC) coupled with protein separation and mass spectrometry. Candidates fulfilling strin- gent criteria for potential substrates or products of the NS3-4A protease were further investigated in different experimental sys- tems as well as in liver biopsies from patients with chronic hep- atitis C. Results: SILAC coupled with protein separation and mass spectrometry yielded > 5000 proteins of which 21 can- didates were selected for further analyses. These allowed us to identify GPx8, a membrane-associated peroxidase involved in disulfide bond formation in the endoplasmic reticulum, as a novel cellular substrate of the HCV NS3-4A protease. Cleavage occurs at cysteine in position 11, removing the cytosolic tip of GPx8, and was observed in different experimental systems as well as in liver biopsies from patients with chronic hepatitis C. Further functional studies, involving overexpression and RNA silencing, revealed that GPx8 is a proviral factor involved in viral particle production but not in HCV entry or RNA replica- tion. Conclusions: GPx8 is a proviral host factor cleaved by the HCV NS3-4A protease. Studies investigating the consequences of cleavage for GPx8 function are underway. The identification of novel cellular substrates of the HCV NS3-4A protease should yield new insights into the HCV life cycle and the pathogenesis of hepatitis C and may reveal novel angles for therapeutic inter- vention.

The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated mitochondrial dysfunction.

Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. In vitro and in vivo studies have shown that alisporivir inhibits hepatitis C virus (HCV) replication, and ongoing clinical trials are exploring its therapeutic potential in patients with chronic hepatitis C. Recent data suggest that the antiviral effect is mediated by inhibition of cyclophilin A, which is an essential host factor in the HCV life cycle. However, alisporivir also inhibits mitochondrial permeability transition by binding to cyclophilin D. Because HCV is known to affect mitochondrial function, we explored the effect of alisporivir on HCV protein-mediated mitochondrial dysfunction. Through the use of inducible cell lines, which allow to investigate the effects of HCV polyprotein expression independent from viral RNA replication and which recapitulate the major alterations of mitochondrial bioenergetics observed in infectious cell systems, we show that alisporivir prevents HCV protein-mediated decrease of cell respiration, collapse of mitochondrial membrane potential, overproduction of reactive oxygen species and mitochondrial calcium overload. Strikingly, some of the HCV-mediated mitochondrial dysfunctions could even be rescued by alisporivir. Conclusion: These observations provide new insights into the pathogenesis of HCV-related liver disease and reveal an additional mechanism of action of alisporivir that is likely beneficial in the treatment of chronic hepatitis C. (HEPATOLOGY 2012).