Melatonin protects against epirubicin-induced cardiotoxicity

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.     

Isolated systolic hypertension in uremic hemodialyzed patients]

Prevalence of Isolated Systolic Hypertension (ISH) defined as systolic blood pressure greater than 160 mmHg and diastolic blood pressure less than 90 mmHg was studied in a population of 148 patients treated by hemodialysis whose 80 had undergone ambulatory blood pressure (ABP) recording during the interdialytic period. All patients were treated 3 times 4 hours a week. ABP was recorded for 48 hours between two sessions of hemodialysis using a Delmar Avionic Presurometer (PIV). Prevalence of ISH was 12.5%, while that of systolic-diastolic hypertension (SDH) was 15%. Average age at the time of the study was respectively 59 +/- 13 yrs ISH and 49 +/- 11 yrs SDH (p less than 0.01) while that of patients with normal blood pressure (N) was 57 +/- 10 yrs. Mean duration of HD treatment was no different between groups: 5.3 +/- 3.5 yrs ISH, 5.0 +/- 4.2 yrs SDH and 5.0 +/- 4.3 yrs N. Causes of end-stage renal disease were similar in each group. All patients with ISH and SDH and 42% of N pts were receiving antihypertensive treatment at the time of ABP recording. Finally, level of anemia and percentage of patients treated by EPO were similar in each group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of life satisfaction index of the elderly people living in nursing homes

The aim of our study was to evaluate the quality of life of the elderly living in nursing homes. A pool of 183 elderly people living in nursing homes were involved in the study. Data regarding the socio-demographic characteristics and life satisfaction index-A (LSI-A) of the participants were collected by means of a questionnaire during face-to-face interviews. The average LSI-A score of the whole group of participants was 25.26+/-5.51. When the mean LSI-A score of participants in relation to their independent variables was analyzed, no statistically significant differences were found for gender, socio-economic status or body mass indexes (BMI). However, the mean LSI-A score of those elderly people who spent some time in leisure activities was significantly higher than those who did not (p=0.03). In the stepwise linear regression analysis, the education level and place of residence were found to be the statistically significant independent predictors of LSI-A scores in the study group (p=0.05, p=0.001).     

PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation

The mechanisms that regulate the differentiation program of multipotential stem cells remain poorly understood. In order to define the cues that delineate endothelial commitment from precursors, we screened for candidate regulatory genes in differentiating mouse embryoid bodies. We found that the PR/SET domain protein, PRDM6, is enriched in flk1(+) hematovascular precursor cells using a microarray-based approach. As determined by 5′ RACE, full-length PRDM6 protein contains a PR domain and four Krüppel-like zinc fingers. In situ hybridization in mouse embryos demonstrates staining of the primitive streak, allantois, heart, outflow tract, paraaortic splanchnopleura (P-Sp)/aorto-gonadal-mesonephric (AGM) region and yolk sac, all sites known to be enriched in vascular precursor cells. PRDM6 is also detected in embryonic and adult-derived endothelial cell lines. PRDM6 is co-localized with histone H4 and methylates H4-K20 (but not H3) in vitro and in vivo, which is consistent with the known participation of PR domains in histone methyltransferase activity. Overexpression of PRDM6 in mouse embryonic endothelial cells induces apoptosis by activating caspase-3 and inducing G1 arrest. PRDM6 inhibits cell proliferation as determined by BrdU incorporation in endothelial cells, but not in rat aortic smooth muscle cells. Overexpression of PRDM6 also results in reduced tube formation in cultured endothelial cells grown in Matrigel. Taken together, our data indicate that PRDM6 is expressed by vascular precursors, has differential effects in endothelial cells and smooth muscle cells, and may play a role in vascular precursor differentiation and survival by modulating local chromatin-remodeling activity within hematovascular subpopulations during development.     

Mechanisms of endothelial differentiation in embryonic vasculogenesis

The formation of new blood vessels in the adult organism not only contributes to the progression of diseases such as cancer and diabetic retinopathy but also can be promoted in therapeutic approaches to various ischemic pathologies. Because many of the signals important to blood vessel development during embryogenesis are recapitulated during adult blood vessel formation, much work has been performed to better-understand the molecular control of endothelial differentiation in the developing embryo. In this review, we describe the current understanding of where endothelial differentiation from pluripotent progenitor cells occurs during development, how this process is controlled at the molecular level, and what model systems can be used to investigate the earliest steps of blood vessel formation.     

Observation of binding and polymerization of Fur repressor onto operator-containing DNA with electron and atomic force microscopes.

The Fur (ferric uptake regulation) protein is a global regulator that, in the presence of Fe2+, represses the expression of a number of iron-acquisition genes and virulence determinants such as toxins. Dark-field electron microscopy of positively stained Fur-DNA complexes in addition to atomic force microscopy allowed direct visualization of Fur interactions with the regulatory regions of aerobactin and hemolysin operons and provided complementary information about the structure of the complexes. According to the DNA used and the protein/DNA ratio, Fur binding to DNA results in partial or total covering of the fragments, indicating that the protein initiates polymerization along the DNA molecules at specific sites. Negative staining of Fur-DNA complexes revealed a well-ordered structure of the polymer suggesting a helical arrangement. Local rigidification of the DNA molecules resulting from Fur binding could be involved in the repression process.     

Case report: HIV negative isolated scrotal Kaposi's sarcoma

INTRODUCTION

Kaposi''s sarcoma (KS) is a rare angioproliferative disorder of the vascular endothelium. The development of KS requires Human Herpes Virus 8 (HHV-8) infection. An associated HIV infection is usually seen. Isolated scrotal KS has rarely been reported. In this article, we present a case of KS that primarily involved the scrotum in a HIV negative patient.

PRESENTATION OF CASE

A 71-year old male patient admitted to the outpatient department due to nodular lesions on the scrotum. The patient declared that these lesions were present for nearly 5 years. Past medical history revealed that he underwent left thoracotomy and upper lobectomy in 2006 for adenosquamous lung carcinoma. Then, he received a single cycle of adjuvant chemotherapy consisted of docetaxel and cisplatin. Physical examination revealed 3 black small nodules on the scrotum. The anti-HIV test was negative. All scrotal lesions were surgically excised. The pathological investigation revealed KS of the lymphangioma-like type.

DISCUSSION

The pathogenesis of KS has still not been clearly elucidated. However, it is known that all forms of KS are associated with HHV-8 infections. A defect in immune system was almost always necessary. Therefore, KS is usually associated with HIV infection. KS of the penis has been reported in HIV negative patients. Very few cases of scrotal KS have been presented. In a recent review, only 1 patient had scrotal KS out of 32 cases with HIV negative KS. In our case, the patient received a cycle of chemotherapy that might affect his immune system. The lymphangioma-like type is a common morphological sub-type. While lymph edemas are commonly observed in this sub-type, no edema in the lymphs was present in our case.

CONCLUSION

Classical KS is generally observed in the lower extremities, it can rarely affect scrotal skin as isolated lesions. Therefore, a careful physical examination should also include scrotum for these patients.