In vivo voltammetry study of the modulatory action of prolactin on the mesolimbic dopaminergic system

The effects of an acute subcutaneous injection of ovine prolactin (PRL) or its vehicle on total motor activity and the extracellular levels of dopamine (DA), DOPAC and ascorbic acid (AA) in the nucleus accumbens were monitored simultaneously in freely behaving male rats. The neurochemical data were obtained by Differential Normal Pulse Voltammetry using electrochemically pretreated carbon fiber microelectrodes and numerical waveform analysis of the catechol peak. PRL treatment increased the extracellular levels of DA and DOPAC in the nucleus accumbens, which is consistent with previous reports using other methodologies. Furthermore, there was a concomitant decrease in the AA signals and motor activity. These findings suggest an antagonistic action of PRL on dopaminergic transmission in the mesolimbic system.     

Cytomics: A multiparametric, dynamic approach to cell research.

Cytomics aims to determine the molecular phenotype of single cells. Within the context of the -omics, cytomics allows the investigation of multiple biochemical features of the heterogeneous cellular systems known as the cytomes. Cytomics can be considered as the science of single cell-based analyses that links genomics and proteomics with the dynamics of cell and tissue function, as modulated by external influences. Inherent to cytomics are the use of sensitive, scarcely invasive, fluorescence-based multiparametric methods and the event-integrating concept of individual cells to understand the complexity and behaviour of tissues and organisms. Among cytomic technologies, flow cytometry, confocal laser scanning microscopy and laser capture microdissection are of great relevance. Other recent technologies based on single cell bioimaging and bioinformatic tools become important in drug discovery and toxicity testing, because of both high-content and high-troughput. The multiparametric capacity of cytomics is very useful for the identification, characterization and isolation of stem cell populations. In our experience, flow cytometry is a powerful and versatile tool that allows quantitative analysis of single molecules, prokaryotic and eukaryotic cells for basic, biotechnological, environmental and clinical studies. The dynamic nature of cytomic assays leads to a real-time kinetic approach based on sequential examination of different single cells from a population undergoing a dynamic process, the in fluxo level. Finally, cytomic technologies may provide in vitro methods alternative to laboratory animals for toxicity assessment.     

Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease

A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO^? to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH₄), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion (). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress () and endothelial function (BH4). There were significantly lower levels of and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.     

Lung transplantation in systemic sclerosis: A single center cohort study

Objective

Lung transplantation (LT) has been proposed as a treatment for advanced interstitial lung disease (ILD) and/or pulmonary hypertension (PH) associated to systemic sclerosis (SSc) but few studies have been reported. The aim of this study was to describe the clinical features, complications and survival of a single-center cohort of patients with SSc that underwent LT and to compare their survival with a group of non-SSc transplanted patients.

Clinical pharmacology of portal hypertension

Portal hypertension is an increase in pressure in the portal vein and its tributaries. It is defined as a portal pressure gradient (the difference in pressure between the portal vein and the hepatic veins) greater than 5 mm Hg. Although this gradient defines portal hypertension, a gradient of 10 mm Hg or greater defines clinically significant portal hypertension, because this pressure gradient predicts the development of varices, decompensation of cirrhosis, and hepatocellular carcinoma. The most direct consequence of portal hypertension is the development of gastroesophageal varices that may rupture and lead to the development of variceal hemorrhage. This article reviews the pathophysiologic bases of the different pharmacologic treatments for portal hypertension in patients with cirrhosis and places them in the context of the natural history of varices and variceal hemorrhage.     

Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens

Background &; Aim. Non alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Population studies have demonstrated that men and posmenopausal women have higher prevalence of NAFLD. The aim was to investigate the prevalence of NAFLD in premenopausal, posmenopausal and polycystic ovary syndrome (PCOS) women.Methods. A cross sectional study carried out at University Hospital in Mexico City from January 2009 to November 2009. One hundred ninety seven women who agreed to participate were divided into groups, comprising 93 with NAFLD and without NAFLD. Anthropometric, metabolic and biochemical variables were measured. Serum estradiol and cortisol concentrations were determined and compared between the groups.Results. Of the 197 patients, 93(47.2%) had NAFLD and 104 (52.8%) did not have NAFLD. The prevalence of NAFLD in premenopausal, postmenopausal and PCOS patients was 32.2, 57.9, and 62%, respectively. Age, BMI, hip to waist ratio, fasting glucose, HOMA-IR, and insulin were significantly higher in NAFLD patients. Women without NAFLD had significantly higher levels of serum estradiol (100 ± 95.4) compared with NAFLD patients (55.5 ± 66.6) p = 0.001. By group with and without NAFLD: premenopausal (55.44±93.3 vs. 128.56 ± 109.22), posmenopausal (44.98 ± 51.41 vs. 42.72 ± 51.48) and PCOS women (64.9 ± 53.3 vs. 101.36 ± 80.89) had significantly different hormone profile.Conclusion. These results suggest that NAFLD is more prevalent in postmenopausal and women with PCOS than those preme-nopausal ones. The estrogens may have a protective effect of against NAFLD in women.     

Liver diseases in Mexico and their associated mortality trends from 2000 to 2007: A retrospective study of the nation and the federal states

Introduction. Liver disease is a major health issue in Mexico. Although several studies have been performed to analyze the impact of liver diseases on the Mexican population, none has compared the prevalence and impact of liver disease between states within Mexico. AIM: To analyze trends in mortality associated with liver diseases from 2000 to 2007 at the national and state levels.Methods. Data was obtained from the Ministry of Health (number of deaths) and the National Population Council (CONAPO) (population at risk) and mortality rates were analyzed using statistical software.Results. Mortality due to viral hepatitis, liver tumors, and cirrhosis increased over the study period. Alcohol-related mortality decreased but was still the main cause of liver-related deaths. Viral hepatitis infection occurred predominantly in the northern states and liver tumors occurred predominantly in the central region. Alcohol-related deaths were elevated along the Pacific shoreline and deaths associated with cirrhosis occurred mainly in the central and southern states.Conclusion. Incidence of liver-related mortality has increased and will continue to do so in the future.     

Vinflunine: a new vision that may translate into antiangiogenic and antimetastatic activity

Microtubules and tubulin are major dynamic and structural cellular components that play a key role in several cell functions, including division, signalling and intracellular trafficking. Normal epithelial cells have a highly structured, rigid cytoskeletal network that is compatible with cell motility. Thus, tubulin and microtubules are compelling cellular targets for chemotherapy. In fact, among anticancer agents, those that target microtubules constitute one of the most effective classes of chemotherapeutics in cancer. The list of compounds that target either tubulin or microtubules is extensive and consists of chemically unique compounds that bind to the tubulin dimers and destabilize microtubules (Vinca alkaloids) and those that bind to the microtubule polymer and stabilize microtubules (taxanes). Tumour-induced angiogenesis, the formation of new capillaries from existing blood vessels, and epithelial-mesenchymal transition are two steps that are critical for both tumour growth and metastatic spread. Three possible mechanisms of action are described with vinflunine, the new-generation Vinca alkaloid to arrive in clinical practice are as follows: it acts against tubulin and microtubules, disrupts newly formed blood vessels and seems to be able to reduce the metastatic process as shown in preclinical studies. These findings support the hypothesis that vinflunine, by blocking microtubule functions that contribute to cell shape, polarization, migration and other processes, might be responsible not only for tumour-cytostatic but also for specific antiangiogenic or antiepithelial-mesenchymal transition effects.     

Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay

Pirfenidone is a non-steroidal antifibrotic compound that has been proposed in clinical protocols and experimental studies as a pharmacological treatment for fibroproliferative diseases. The objective of this study was to determine the genotoxicity or cytotoxicity of three doses of pirfenidone using the micronuclei test in peripheral blood erythrocytes of rodent models. Pirfenidone was administered orally to Balb-C mice for 3 days, and also was administered topically to hairless Sprague Dawley rats during the final stage of gestation. Mice were sampled every 24 h over the course of 6 days; pregnant rats were sampled every 24 h during the last 6 days of gestation, and pups were sampled at birth. Blood smears were analyzed and the frequencies of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and the proportion of polychromatic erythrocytes (PCEs), were recorded in samples from mice, pregnant rats and rat neonates. Increases in MN frequencies (p < 0.03) were noted only in the positive control groups. No genotoxic effects or decreased PCE values were observed neither in newborn rats transplacentally exposed to pirfenidone, or in two adult rodent models when pirfenidone was administered orally or topically.