Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass

Skeletal muscle hypertrophy is a result of increased load, such as functional and stretch-overload. Activation of satellite cells and proliferation, differentiation and fusion are required for hypertrophy of overloaded skeletal muscles. On the contrary, a dramatic loss of skeletal muscle mass determines atrophy settings. The epigenetic changes involved in gene regulation at DNA and chromatin level are critical for the opposing phenomena, muscle growth and atrophy. Physiological properties of skeletal muscle tissue play a fundamental role in health and disease since it is the most abundant tissue in mammals. In fact, protein synthesis and degradation are finely modulated to maintain an appropriate muscle mass. When the molecular signaling is altered muscle wasting and weakness occurred, and this happened in most common inherited and acquired disorders such as muscular dystrophies, cachexia, and age-related wasting. To date, there is no accepted treatment to improve muscle size and strength, and these conditions pose a considerable anxiety to patients as well as to public health. Several molecules, including Magic-F1, myostatin inhibitor, IGF, glucocorticoids and microRNAs are currently investigated to interfere positively in the blueprint of skeletal muscle growth and regeneration.     

Volumetric MRI analysis of hippocampal subregions in Cushing's disease: A model for glucocorticoid neural modulation

Several preclinical studies have demonstrated neuronal effects of glucocorticoids on the hippocampus (HC), a limbic structure with anterior-posterior anatomical and functional segmentation. We propose a volumetric magnetic resonance imaging analysis of hippocampus head (HH), body (HB) and tail (HT) using Cushing's disease (CD) as model, to investigate whether there is a differential sensitivity to glucocorticoid neuronal damage in these segments. We found a significant difference in the HH bilaterally after 12 months from trans-sphenoidal surgical selective resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary micro-adenomas. This pre-post surgery difference could contribute to better understand the pathopysiology of CD as an in vivo model for stress-related hypercortisolemic neuropsychiatric disorders.     

Nevirapine-induced side effects in pregnant women: experience of a Brazilian university hospital.

Nevirapine-based therapy is associated with increased frequency of adverse events among HIV-infected pregnant women. The aim of this article was to evaluate the incidence of adverse effects in HIV-infected women who started nevirapine during pregnancy. A retrospective study was performed in our center between January 2003 and December 2006 analyzing all women prescribed nevirapine during pregnancy. Women presenting any risk factor for hepatotoxicity were excluded from the analysis. Patients were divided into two groups according to the presence or absence of adverse effects, and a correlation to CD4 counts was performed. Liver function abnormality was graded according to the Division of AIDS toxicity guidelines. A total of 170 women initiated nevirapine during pregnancy, but only 133 were included in the study. Twenty-seven women (20.3%) presented adverse effects, skin rash accounting for 77.8% (21/27 women) and liver function abnormalities for 22.2% (6/27) of the cases. Baseline CD4 counts, viral loads and transaminases were similar in both groups. All nevirapine side effects were developed in less than seven weeks. Four of 31 women with CD4 counts <250 cells/microL (12.9%) and 23 of 102 women with CD4 counts > or = 250 cells/microL (22.5%) developed adverse events. All patients who experienced hepatotoxicity had pretreatment CD4 counts > or =250 cells/microL. The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analyzing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts > or =250 cells/microL.     

Quality of life in systemic lupus erythematosus

The SF-20 and the SF-36 are the most frequently used questionnaires for assessing the quality of life in SLE patients. The SF-36 is actually considered the most suitable for this disease, due to the inclusion of fatigue, a manifestation frequently observed in SLE patients. Using these instruments, it has been clearly demonstrated that patients with SLE have a worse quality of life than healthy people of the same age. Some aspects of daily life, like physical activity, job, social relationship and vitality, are particularly affected. In the majority of studies, an inverse relation between quality of life and disease activity has been observed. The influence the damage has on the quality of life is more complex, since a greater number of variables are involved. In fact, the amount of damage largely depends on the organ involved and on functional impairment resulting from it. To explain the variability in the quality of life among different patients, it is important to consider, besides the clinical complaints, the psycho-social dimension of each person. In fact, some SLE patients, unlike others, cope well with the disease. People behave differently when faced with critical situations, i.e. after being diagnosed with a chronic disease; their reaction depends on the degree of support they receive from family, friends and colleagues, and from the different strategies of coping, that they use.     

Molecular characteristics of two esophageal carcinosarcomas: a hint for theclonality of carcinomatic and sarcomatic tumor components

AIM To study the clonality of the esophageal carcinosarcoma by using molecular approaches.METHODS Two esophageal carcinosarcomas were included in the study. Tumor area from dysplasticlesion, squamout cell carcinoma, basaloid cell carcinoma and spindle cell elements were microdissectedseparately. Each element was analyzed with 14 microsatellite markers and direct sequenced for p53 gene andras gene mutation.RESULTS Both tumors displayed a typical histologic feature of carcinosarcoma. Both cases showed thedivergent differentiation by immunohistochemistry study. In case 1 the identical LOH at p53 and hMLH1 lociwas detected. The heterogenous LOH was detected only in carcinosarcoma at RB1 and BRCA1 loci, whilethe LOH at ACTC locus was seen only in sarcoma. The same mutation of the splice site of exon 6-intron 6displayed in the two tumor elements. In case 2, a coordinate LOH at RB locus was demonstrated in threetypes of tumor elements: sqamous carcinoma, basaloid carcinoma and spindle cell element. A heterogenousLOH was seen only in spindle cells at TAP1 locus. No mutation in exon 5-8 of p53 gene has been found incase 2. No mutation of K-ras gene was found.CONCLUSION Although the different differentiation, the two elements of esophageal carcinosarcoma mayhave a single clonality. The p53 gene mutation occurred before the two differentiation directions switched.The distinct molecular genotype can be determined through molecular biological analysis. The microsatelliteprofiling can serve as an approach to find out which genetic alteration occurs before or after thedifferentiation is determines.