Role of maraviroc and/or rapamycin in the liver of IL10 KO mice with frailty syndrome.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study.

Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.

Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.

Kinetics of formic acid dehydration on Pt electrodes by time-resolved ATR-SEIRAS.

The potential dependence of the rate of dehydration of formic acid to adsorbed CO (COad) on Pt at pH 1 has been studied on a polycrystalline Pt surface by time-resolved surface-enhanced infrared absorption spectroscopy in the attenuated total reflection mode (ATR-SEIRAS) with simultaneous recording of current transients after a potential step. A range of formic acid concentrations has been used to obtain a deeper insight into the mechanism of the reaction. The experiments have allowed us to confirm that the potential dependence of the rate of dehydration has a bell shape, going through a maximum around the potential of zero total charge (pztc) of the most active site. The analysis of the integrated intensity and frequency of the bands corresponding to COL and COB/M shows a progressive population of the active sites on the surface. The observed potential dependence of the rate of formation of COad is consistent with a mechanism in which the reversible electroadsorption of HCOOad is followed by its rate-determining reduction to COad.

Low availability of functional seed trait data from the tropics could negatively affect global macroecological studies, predictive models and plant conservation.

BACKGROUND: Plant seeds have many traits that influence ecological functions, ex situ conservation, restoration success and their sustainable use. Several seed traits are known to vary significantly between tropical and temperate regions. Here we present three additional traits for which existing data indicate differences between geographical zones. We discuss evidence for geographical bias in availability of data for these traits, as well as the negative consequences of this bias. SCOPE: We reviewed the literature on seed desiccation sensitivity studies that compare predictive models to experimental data and show how a lack of data on populations and species from tropical regions could reduce the predictive power of global models. In addition, we compiled existing data on relative embryo size and post-dispersal embryo growth and found that relative embryo size was significantly larger, and embryo growth limited, in tropical species. The available data showed strong biases towards non-tropical species and certain families, indicating that these biases need to be corrected to perform truly global analyses. Furthermore, we argue that the low number of seed germination studies on tropical high-mountain species makes it difficult to compare across geographical regions and predict the effects of climate change in these highly specialized tropical ecosystems. In particular, we show that seed traits of geographically restricted páramo species have been studied less than those of more widely distributed species, with most publications unavailable in English or in the peer-reviewed literature. CONCLUSIONS: The low availability of functional seed trait data from populations and species in the tropics can have negative consequences for macroecological studies, predictive models and their application to plant conservation. We propose that global analyses of seed traits with evidence for geographical variation prioritize generation of new data from tropical regions as well as multi-lingual searches of both the grey- and peer-reviewed literature in order to fill geographical and taxonomic gaps.

Elevated levels of serum CDCP1 in individuals recovering from severe COVID-19 disease.

BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.

HIV/HBV coinfection: temporal trends and patient characteristics, Spain, 2002 to 2018.

BackgroundRecent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking.AimLeveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002.MethodsThis cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients.ResultsThe prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL.ConclusionsThe prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study.

BACKGROUND: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). METHODS: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). RESULTS: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. CONCLUSIONS: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads.

Implications of maraviroc and/or rapamycin in a mouse model of fragility.

BACKGROUND: As age increases, the risk of developing fragility also increases. Improving the knowledge of frailty could contribute to maintaining the functional ability of elderly people. Interleukin (IL)-10 homozygous knockout mice (IL-10tm/tm [IL10KO]) constitute an excellent tool for the study of frailty. Because patients with frailty demonstrate an overexpression of CCR5, rapamycin (RAPA) and/or maraviroc (MVC), two molecules able to decrease CCR5 expression, were evaluated. RESULTS: Muscle myostatin was reduced in all the therapeutic groups but the MVC group (p <0.001 for RAPA and MVC-RAPA) and in serum samples (p <0.01 for all the groups). Serum CK levels were also significantly lower in MVC and RAPA groups (p <0.01 in both cases). Lower AST levels were observed in all the therapeutic groups (p <0.05 for all of them). The apoptotic effector caspase-3 was significantly lower in MVC and RAPA groups (p<0.05 in both cases). Combined treatment with MVC-RAPA showed a synergistic increase in p-AKT, p-mTOR and SIRT1 levels. CONCLUSIONS: MVC and RAPA show a protective role in some factors involved in frailty. More studies are needed to prove their clinical applications. MATERIAL AND METHODS: Eighty male homozygous IL10KOs were randomly assigned to one of 4 groups (n= 20): i) IL10KO group (IL10KO); ii) IL10KO receiving MVC in drinking water (MVC group), iii) IL10KO receiving RAPA in drinking water (RAPA group), and finally, iv) MVC-RAPA group that received MVC and RAPA in drinking water. Blood and muscle samples were analysed. Survival analysis, frailty index calculation, and functional assessment were also performed.

El eje microbiota-intestino-cerebro y sus grandes proyecciones / The microbiota-gut-brain axis and its great projections

Introducción. Se denomina microbiota al conjunto de millones de microorganismos que conviven de manera simbiótica en nuestro organismo. Este conjunto bacteriano, que se localiza principalmente en el tracto digestivo, se distribuye a lo largo de los diferentes órganos en función de las propiedades químicas. Los factores que influyen en su composición son múltiples (dieta, hábitos individuales, fármacos). La microbiota colabora en varias funciones, como pueden ser el metabolismo o la inmunidad. Desarrollo. En los últimos años se ha puesto de relieve el papel bidireccional de la microbiota del tracto digestivo y del sistema nervioso central, es el denominado eje intestino-cerebro. En lo que a este eje se refiere, se cree que la comunicación se produce a través de tres vías: el nervio vago, la vía sistémica (mediante la liberación de hormonas, metabolitos y neurotransmisores) y el sistema inmune (por la acción de las citocinas). Conclusiones. Aunque aún quedan muchas incógnitas por esclarecer, este eje se postula como una posible base patógena para numerosos trastornos neurológicos de gran impacto sanitario, como la enfermedad de Alzheimer, la enfermedad de Parkinson o la esclerosis múltiple. En el momento actual se están llevando a cabo estudios que intentan evaluar el impacto de los probióticos sobre algunas de estas enfermedades neurológicas

Introduction. The microbiota is the set of millions of microorganisms that coexist in a symbiotic way in our body. It is mainly located in the digestive tract, being distributed in function of the chemical properties and the functions of the different organs. The factors that influence its composition are multiple (diet, individual habits, diseases or drugs). It also participates in several functions of the organism such as metabolism, immunity or even the function of the central nervous system. Development. This last interrelationship is called: gut-brain axis. For years the relationship between the microbiota and the central nervous system has been known and how they influence one over the other. It is postulated that communication occurs through three systems: the vagus nerve, the systemic pathway (with the release of hormones, metabolites and neurotransmitters) and the immune system (by the action of cytokines). Conclusions. There are still many unknowns to be clarified in this field, but this microbiota-intestine-brain relationship is postulated as a possible pathogenic basis for neurological diseases of great health impact such as Alzheimer, Parkinson or multiple sclerosis. There are currently studies with probiotics with hopeful results in patients with Alzheimer's disease

Theoretical insight into the vibrational spectra of metal-water interfaces from density functional theory based molecular dynamics.

Understanding the structures of electrochemical interfaces at the atomic level is key to developing efficient electrochemical cells for energy storage and conversion. Spectroscopic techniques have been widely used to investigate the structures and vibrational properties of the interfaces. The interpretation of these spectra is however not straightforward. In this work, density functional theory based molecular dynamics simulations were performed to study the vibrational properties of the Pt(111)- and Au(111)-water interfaces. It was found that the specific adsorption of some surface water on Pt(111) leads to a partial charge transfer to the metal, and strong hydrogen bonding with neighbouring water molecules, which resolves the interpretation of the elusive O-H stretching peak at around 3000 cm-1 observed in some experiments.

Maraviroc improves hepatic triglyceride content but not inflammation in a murine nonalcoholic fatty liver disease model induced by a chronic exposure to high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. Its severity ranges from simple steatosis to cirrhosis. C-C chemokine ligand type 5 or RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted) plays an important role in the progression of hepatic inflammation and fibrosis. Our objective was to examine the preventive and therapeutic effects of maraviroc (MVC), a C-C chemokine receptor 5 antagonist, on liver pathology in an NAFLD mouse model. A total of 60 male C57BL/6 mice were randomly assigned to 1 of 4 groups: (1) high-fat diet (HFD) group or control group, (2) preventive group (HFD group plus MVC in drinking water since the beginning of the study), (3) early-therapeutic group (HFD group plus MVC in drinking starting at week 24 of the study), and (4) late-therapeutic group (HFD group plus MVC in drinking water starting at week 36 of the study). All mice were sacrificed at week 48. The hepatic triglyceride concentration in the HFD group was significantly higher than that in the groups treated with MVC at any time. Gene expression associated with lipogenesis (diacylglycerol acyltransferase 2 and proliferator-activated receptor-γ), insulin resistance (insulin receptor substrate-2), and ß-oxidation (carnitine palmitoyltransferase 1A and acyl-CoA oxidase) was significantly reduced in all the groups treated with MVC. In summary, the beneficial effect of MVC on hepatic steatosis is maintained throughout the study.

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant.

BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Maraviroc ameliorates the increased adipose tissue macrophage recruitment induced by a high-fat diet in a mouse model of obesity.

BACKGROUND: Any strategy designed to decrease the macrophage content in adipose tissue (AT) is of great value as a way to decrease inflammation in this fat depot and also as a way to prevent or treat obesity and associated disorders. Maraviroc (MVC), a CCR5 antagonist approved for the treatment of HIV-infected patients, has beneficial effects on metabolism. The objective of this study was to investigate the effects of MVC on AT macrophage recruitment in a mouse model of obesity. The plausible underlying mechanisms of action were also investigated. METHODS: 32 male C57BL/6 mice were randomly assigned to the following groups: control, MVC (300 mg/l MVC in drinking water), high-fat diet (HFD) or HFD+MVC. After 16 weeks of treatment, histopathological and molecular analyses were performed on epididymal fat. RESULTS: Our results demonstrated that MVC reduced the presence of macrophages in epididymal fat despite the ingestion of an HFD. The inhibition of MCP-1 gene expression and JNK signalling pathway along with the upregulation of protective cytokines such as cardiotrophin-1 could contribute to these actions. MVC effects on AT macrophage recruitment were associated with a lower body weight gain and a partial improvement in insulin resistance despite an HFD. CONCLUSIONS: We have demonstrated the ability of MVC to ameliorate the increased AT macrophage recruitment induced by an HFD in a mouse model of obesity. These actions could be of interest when designing antiretroviral treatments in HIV-patients.

Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients / / Maraviroc modifica la composición de la microbiota intestinal en un modelo animal de obesidad: una posible opción terapéutica para prevenir los trastornos metabólicos en pacientes infectados por el VIH

Introduction. The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the develop-ment of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity. Methods. Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut. Results. Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales. Conclusions. MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients (AU)

Introducción. La proporción de pacientes VIH con sobrepeso/obesidad ha aumentado en los últimos años. Éstos tienen un mayor riesgo metabólico/cardiovascular que los no obesos. La modulación de la microbiota intestinal se considera una herramienta prometedora para prevenir el desarrollo de obesidad y de sus trastornos asociados. El objetivo de este estudio fue investigar el impacto de maraviroc (MVC), un antagonista de CCR5 empleado para el tratamiento de pacientes VIH, sobre la composición de la microbiota intestinal en un modelo murino de obesidad. Métodos. 32 ratones macho C57BL/6 fueron asignados a los grupos: a) Control b) MVC (control más 300 mg/L de MVC), c) dieta alta en grasa (HFD) o d) HFD/MVC (HFD más 300 mg/L MVC). El peso corporal y la ingesta de alimentos se registraron cada 2-3 días. Los ratones fueron sacrificados a las 16 semanas. Se analizaron por qPCR cuatro órdenes bacterianos. Resultados. Los ratones HFD mostraron un aumento significativo en Enterobacteriales (p<0,001 vs. control). El tratamiento con MVC disminuyó significativamente este orden (p<0,05 vs. Control y p<0,001 vs. HFD). Enterobacteriales se asoció positivamente con el aumento de peso, la resistencia a la insulina y el hígado graso. La ingesta de una HFD indujo una disminución significativa de Bacteroidales y Clostridiales (p<0,05 y p<0,01 respectivamente). MVC disminuyó la presencia Bacteroidales en animales control (p<0,05) e incrementó su presencia en HFD/MVC (p=0,01 vs. HFD). No se observaron efectos directos de MVC sobre Clostridiales y Lactobacillales.Conclusiones. MVC podría constituir una nueva opción terapéutica para prevenir la obesidad y sus trastornos relacionados en pacientes infectados por el VIH (AU)

Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients.

INTRODUCTION: The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the development of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity. METHODS: Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut. RESULTS: Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales. CONCLUSIONS: MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients.

Photosynthetic performance and leaf water potential of gulupa (Passiflora edulis Sims, Passifloraceae) in the reproductive phase in three locations in the colombian andes / Desempeño fotosintético y potencial hídrico foliar de gulupa (Passiflora edulis Sims, Passifloraceae) en estado reproductivo en tres localidades de los Andes colombianos

Gulupa, Passiflora edulis Sims (Passifloraceae), is an important fruit due to its organoleptic and nutritional characteristics and its demand in the international market; however, very few studies have been conducted for studying its Ecophysiology. Until now, this crop has spread throughout the country through empirical knowledge without data that indicate the zones that are more suitable for its cultivation. For this reason, gas exchange, chlorophyll fluorescence (photosystem II operating efficiency and maximum quantum efficiency of photosystem II photochemistry) and leaf water potential were measured in three different locations of Cundinamarca department (Chia [2610 m a.s.l., 14 °C], Granada [2230 m a.s.l., 15 °C] and Tena [2090 m a.s.l., 17 °C]), whose climatic conditions were monitored with meteorological stations to evaluate the physiologic performance in each location related to the environmental factors. The results indicate that, even though the photosynthetic capacity was similar and high in Granada and Tena, the water status of the plant, the stomatal control of water loss and recovery of photosystems during the night were more efficient in Granada (p < 0.05). In Tena, the small differences between day and night temperature, humidity, and vapor pressure deficit (VPD) would limited the night water recovery in the plants. Meanwhile, in Chia, the increase of VPD during the day and the low temperatures would decreased the water potential both during the day and during the night, as well as the recovery of photosystem II. Therefore, in conclusion the climatic conditions similar to Granada, which are 18/13 °C day/night, a VPD close to 0.5 KPa, and radiation that did not exceed 1000 μmol photons/m²s favored the good physiological performance of gulupa.

La gulupa, Passiflora edulis Sims (Passifloraceae) es un frutal importante debido a sus características organolépticas, nutricionales y su demanda en el mercado internacional; sin embargo, existen muy pocos estudios relacionados con su ecofisiología. Hasta el momento, el cultivo se ha extendido a través del país por medio de conocimiento empírico sin tener datos que sustenten las zonas más apropiadas para su cultivo. Por esta razón, en el presente estudio se midió el intercambio de gases, la fluorescencia de la clorofila (factor de eficiencia del fotosistema II y eficiencia cuántica fotoquímica máxima del fotosistema II) y el potencial hídrico foliar en tres localidades diferentes del departamento de Cundinamarca (Chía [2610 m s.n.m., 14 °C], Granada [2230 m s.n.m., 15 °C] y Tena [2090 m s.n.m., 17 °C]), cuyas condiciones climáticas fueron monitoreadas con estaciones meteorológicas para evaluar el desempeño fisiológico en cada localidad y relacionarlo con los factores ambientales. Los resultados indican que aunque la capacidad fotosintética fue alta y similar en Granada y Tena, el estado hídrico de la planta, el control estomático de la pérdida de agua y la recuperación de los fotosistemas durante la noche fueron más eficientes en Granada (p < 0,05). En Tena, la estrecha diferencia entre los valores día/noche de temperatura, humedad y déficit de presión de vapor (DPV) limitarían la recuperación hídrica de la planta, mientras que en Chía el aumento de DPV en el día, y las bajas temperaturas disminuirían el potencial hídrico, tanto durante el día como durante la noche, así como la recuperación del fotosistema II. Por tanto, en conclusión, condiciones climáticas cercanas a las de Granada; 18/13 °C día/noche, DPV de 0,5 KPa, y una radiación que no exceda los 1000 μmol fotones/ m²s favorecen el buen desempeño de la planta.

Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load.

INTRODUCTION: Several factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV-infected patients with undetectable HIV viral load (VL). For this reason, we performed the present study. MATERIALS AND METHODS: Observational and multicenter study (2008-2012) conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c) virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART) (≥6 months) and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model) and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test. RESULTS: A total of 608 patients were included (median age 29.4 years, 71.7% men). Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02) and the duration of the coinfection (p=0.001). CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056). CONCLUSIONS: In HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

Dual therapy with darunavir/r plus etravirine is safe and effective as switching therapy in antiretroviral experienced HIV-patients. The BITER Study.

INTRODUCTION: Switching therapy studies are usually designed as second-line antiretroviral treatment (ART) in patients without previous virologic failures. Combined ART (cART) with DRV/r and ETR has a good pharmacokinetic profile, high genetic barrier and has been proved as rescue therapy. The aim of our study was to analyze efficacy and safety of therapy with DRV/r plus ETR in treatment experienced HIV-patients with previous therapeutic failures that need to switch ART. We present results at first 24 weeks. METHODS: Multicentre retrospective observational study. INCLUSION CRITERIA: adult HIV-patients on ART with HIV-VL <1000 cop/mL who started their ART with DRV/r (600/100 bid or 800/100 qd)+ETR by adverse events, non-adherence, tolerability or prevention of future complications. Patients with acute AIDS events, HBV, pregnancy, drug addiction or previous selected mutations to DRV or ETR were excluded. RESULTS: Ninety-nine patients were included, mean age: 47 years (r: 22-79); 70% men, 40.4% previous AIDS event and 39.3% HCV. Ninety-one patients had received ≥3 cART regimens and 45≥5, 75 patients had HIV-VL <50 cop/mL and 24 low-level viremia (LLV): 297.5±261.4 cop/mL, CD4+ 568±279 cells/µL. ART before switching: NRTI+PI/r (33%), NNRTI (17%), PI/r+NNRTI (23%), PI/r+INI (13%), other (14%). Main reason to switching was: toxicity/intolerance 50 patients (renal 32%, gastrointestinal: 14%, hyperlipidaemia 10%; osteopenia/osteoporosis: 6%); improving adherence 26 patients; prevention of complications 19 patients. Nine subjects withdrew ART during follow-up because: intolerance or new toxicity three; non-adherence two; simplification to DRV/r monotherapy two; persistence of previous toxicity one; virologic failure one. At week 24, among patients who continued with DRV/r+ETR (n=90): 81 (89%) had VL<50 cop/mL, in those with with HIV-VL<50 at baseline (67/90), 94% persisted with <50 cop., and in those with LLV (24/90), 61% (n=14) achieved a VL<50 cop. We didn't observe any significant difference in lab parameters between baseline and week 24. Estimated glomerular filtrate rate increased from 83.4±24.7 to 88.5±56.8 mL/min, p=NS. Regarding reason to switching, it improved in 42 cases, no changes: 20 cases; worsened: 4 cases, and non-applicable or unknown: 24 cases. CONCLUSIONS: Switching to dual therapy with DRV/r+ETR is an effective strategy in selected heavily experienced ART patients, even in those with LLV (<1000 cop/mL). This cART is safe and well tolerated, can reduce number of pills and improve adherence.

Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model. METHODS: A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed. RESULTS: Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group. CONCLUSIONS: Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD.