Immune and autoimmune disorders in HCV chronic liver disease: personal experience and commentary on literature

HCV chronic liver disease can be associated with a plethora of immune and autoimmune perturbations and many authors claim that HCV chronic infection can play an important role in the pathogenesis of these disorders. To compare our experience with literature reports, we performed a retrospective study on the case histories of 265 patients with HCV chronic liver disease, evaluating the type and prevalence of the associated immune and autoimmune manifestations. We found that the patients with HCV chronic liver disease can present arthromyalgias (7.1% of the patients), Sj?rgen's syndrome (5.2%), thyroiditis (4.1%), rheumatoid arthritis (2.2%), autoimmune thrombocytopenia (2.6%), mixed cryoglobulinemia (1.5%), autoimmune anemia (0.3%) and oral lichen planus (0.3%). We claim that HCV liver infection is able to induce immune and autoimmune perturbations, without playing a significant role in the pathogenesis of a well-defined disorder.     

p27kip1 overexpression promotes paclitaxel-induced apoptosis in pRb-defective SaOs-2 cells

p27kip1 is a cyclin-dependent kinase (CDK) inhibitor, which controls several cellular processes in strict collaboration with pRb. We evaluated the role of p27kip1 in paclitaxel-induced apoptosis in the pRb-defective SaOs-2 cells. Following 48 h of exposure of SaOs-2 cells to 100 nM paclitaxel, we observed an increase in p27kip1 expression caused by the decrease of the ubiquitin-proteasome activity. Such increase was not observed in SaOs-2 cells treated with the caspase inhibitors Z-VAD-FMK, suggesting that p27kip1 enhancement at 48 h is strictly related to apoptosis. Finally, we demonstrated that SaOs-2 cells transiently overexpressing the p27kip1 protein are more susceptible to paclitaxel-induced apoptosis than SaOs-2 cells transiently transfected with the empty vector. Indeed, after 48 h of paclitaxel treatment, 41.8% of SaOs-2 cells transiently transfected with a pcDNA3-p27kip1 construct were Annexin V-positive compared to 30.6% of SaOs-2 cells transfected with the empty vector (P < 0.05). In conclusion, we demonstrated that transfection of the pRb-defective SaOs-2 cells with the p27kip1 gene via plasmid increases their susceptibility to paclitaxel-induced apoptosis. The promoting effect of p27kip1 overexpression on apoptosis makes p27kip1 and proteasomal inhibitors interesting tools for therapy in patients with pRb-defective cancers.     

Comparative study with two different enrichments in the culture media used in the disinfectant efficacy assay

Recent changes in Brazilian legislation for commercial disinfectants have been published due to the recent epidemic of nosocomial infections caused by rapidly growing mycobacteria (RGM) in many states of Brazil over the last 8 years. One of these documents requires that all the manufacturers provide evidence of efficacy of sterilizing and disinfectant products, used for semi critical medical devices, against the Mycobacterium bovis BCG Moreau and Mycobacterium abscessus subsp. bolletii INCQS 00594 strains by using the Confirmative in vitro Test for Determining Tuberculocidal Activity of Disinfectants recommended by the Association of Official Analytical Chemists. These changes have caused additional costs and increased problems for importation of enrichment products at national laboratories where disinfectant efficacy assay service is performed. Middlebrook ADC Enrichment (ADC) is provided by a unique manufacturer and used in the official protocol. The aim of the present study was to evaluate an alternative in house low-cost enrichment composed of fetal bovine serum and glucose (FBSG) with ADC for performance of disinfectant efficacy assay against mycobacteria. After obtaining the growth curves for M. abscessus ATCC 19977, M. abscessus subsp. bolletii INCQS 00594, Mycobacterium chelonae ATCC 35752, and Mycobacterium fortuitum ATCC 6841 by using ADC enrichment and FBSG in Kirchners and 7H9 culture media. Through statistical analysis via the Kruskal-Wallis test on the evaluation of microorganism growth rate, it was observed that there was no inhibition of RGM growth by any of the enrichments used. These results suggest that low-cost enrichment FBSG may be used as a potential substitute of ADC for composition of media for mycobacterial growth, including in disinfectant tests.     

Clonal diversity and conservation genetics of the medicinal plant Carapichea ipecacuanha (Rubiaceae)

The roots of the understorey shrub Carapichea ipecacuanha (ipecac) have medicinal properties, and the uprooting of wild plants has supplied most of the world demand for this species. Although under severe population decline, C. ipecacuanha lacks legal protection. In the wild, the aerial stems of ipecac clump together to form clusters with well-defined borders. Cluster size may range from several to hundreds of aerial stems. To investigate the extent of clonality among aerial stems in ipecac clusters, we sampled 50 wild clusters (a total of 291 aerial stems) and screened them with 89 inter-simple sequence repeat (ISSR) markers. The 291 aerial stems were grouped into 42 putative clones. The clonal groups generally consisted of aerial stems from the same cluster, and there was little or no genetic differentiation among aerial stems at the cluster level. These findings suggest that strategies designed to conserve ipecac in situ should not rely upon census data, which are based on the number of aerial stems per cluster and the number of clusters per population, because such data greatly underestimate the species effective population size and genetic diversity. Our results also indicate that this species needs protection at a federal level.     

Atrophic cardiac remodeling induced by taurine deficiency in wistar rats

Introduction

Micronutrient deficiency is observed in heart failure patients. Taurine, for example, represents 50% of total free amino acids in the heart, and in vivo studies have linked taurine deficiency with cardiomyopathy.

Methods

Thirty-four male Wistar rats (body weight = 100 g) were weighed and randomly assigned to one of two groups: Control (C) or taurine-deficient (T (-)). Beta-alanine at a concentration of 3% was added to the animals’ water to induce taurine deficiency in the T (-) group. On day 30, the rats were individually submitted to echocardiography; morphometrical and histopathological evaluation and metalloproteinase activity, oxidative stress and inflammation evaluation were performed. Tissue samples were collected to determine the taurine concentration in the heart.

Results

Taurine deficiency led to decreases in: ventricular wall thickness, left ventricle dry weight, myocyte sectional area, left ventricle posterior wall thickness and ventricular geometry. With regard to heart function, the velocity of the A wave, the ratio between the E and A wave, the ejection fraction, fractional shortening and cardiac output values were decreased in T (-) rats, suggesting abnormal diastolic and systolic function. Increased fibrosis, inflammation and increased activation of metalloproteinases were not observed. Oxidative stress was increased in deficient animals.

Conclusions

These data suggest that taurine deficiency promotes structural and functional cardiac alterations with unique characteristics.