Inhibition of HSP90 could be possible mechanism for anti-cancer property of amniotic membrane

Amniotic membrane (AM), the innermost layer of the fetal membrane, is considered as a suitable candidate for cancer therapy. In order to develop the AM as a new cancer therapeutic approach, it is essential to understand the molecular mechanism of the AM anti-cancer properties. Previous studies demonstrated that anti-proliferative effects of the AM on tumor cells were associated with induction of cell cycle arrest. Moreover, it has been shown that unknown substances in the AM induce apoptosis in cancer cells and inhibit angiogenesis in tumors. In contrast to the effects of the AM, heat shock proteins (HSPs), in particular HSP90, play a crucial role in development of tumorgenesis. HSP90 inhibits apoptosis in cancer cells and enhances angiogenesis and cell cycle progression. Based on the opposite effects of the amniotic membrane ingredients and HSP90, we hypothesized here that possible mechanism of the AM anti-cancer effects is through inhibition of HSP90.     

Evolution and species-specific conservation of toll-like receptors in terrestrial vertebrates

Toll-like receptors (TLRs) are known for their essential roles in promotion of innate immunity and induction of adaptive immunity through recognition of pathogen-associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs). TLR genes are excellent models for the study of the selective pressure enforced by microorganisms on the host genome. Phylogenetic analyses have shown that interactions between pathogens and immune systems have changed during evolution. Selective pressure for maintenance of specific pathogen recognition has led to evolution of TLRs under both positive and purifying selection. However, intracellular and cell-surface TLRs have been affected differently due to their variation in conservational constraints. In this review, we summarize some of the main studies on the influence of selection on shaping the evolution of several TLR gene families in different terrestrial vertebrate species. We also describe the effect of evolution on the function of different TLRs and their specific conservations in these species and show similarities and differences in evolutionary patterns of TLR orthologs among species as well as among TLR gene families.     

Mutations in NLRP7 and KHDC3L Confer a Complete Hydatidiform Mole Phenotype on Digynic Triploid Conceptions

Digynic triploidy is classically associated with a severely growth restricted fetus and a small nonmolar placenta. However, in genotyping hydatidiform moles as part of clinical practice, we identified two digynic triploid conceptions presenting with histopathological features of classical complete hydatidiform mole (CHM). Both cases occurred in women with a history of previous molar pregnancies and no normal pregnancies. Pathological review and genotyping of other molar pregnancies in these cases showed them to be typical CHM with negative p57^KIP2 immunostaining of the cytotrophoblast cells and villous stroma and to be diploid but biparental, confirming a diagnosis of familial recurrent hydatidiform mole (FRHM). Mutation screening of NLRP7 had identified a homozygous duplication, leading to a truncated protein, in case 1 whereas mutation screening of KHDC3L (C6orf221) in case 2 showed both the proband and her sister to be compound heterozygotes for mutations in KHDC3L. The observation of a single digynic, triploid conception presenting as a CHM in women with FRHM, where other pregnancies are diploid and biparental, supports the hypothesis that the role of both NLRP7 and KHDC3L in pregnancy is in setting and/or maintaining the maternal imprint. Clinically, a diagnosis of FRHM should be considered in women with genetically unusual conceptions that are phenotypically CHM.     

Microanatomical study of testis in juvenile ostrich (Struthio camelus)

The majority of investigations on the testis, as the main organ of male reproductive system, have been performed in mammalian species, with few studies on bird species. Thus, the structure of the ostrich testis remains largely unknown. The aim of this study was to investigate the microanatomical characteristics of the testis in five juvenile ostriches. A stereological study was performed according to the Delesse principle. The mean volume fraction of the seminiferous tubules was 0.569, and the mean volume of the seminiferous tubules in an average testis was 1.04 cm³. The Paraffin-embedded sections were stained with hematoxylin and eosin, Masson’s trichrome, Alcian blue, and periodic acid–Schiff stains. Histological studies revealed that the spermatogonial stem cells and Sertoli cells were localized inside the seminiferous tubules, close to the basement membrane. Inside the tubules a few meiotic cells up to the spermatozoa stage were located in a centripetal manner. Outside the tubules, one to three layers of euchromatic peritubular myoid cells were present, surrounded by loose interstitial connective tissue. A thick tunica albuginea contained many myoid cells and some rete ducts, with the latter extending from the hilus to the free surface of the testis. Straight seminiferous tubules were distributed in the lateral surfaces and hilar portions of the capsule but were rare in the free surface. These capsular rete ducts may participate in testicular fluid transit from the distal tubules through the capsule.     

Pulmonary and extra-pulmonary manifestations of sarcoidosis

Background:

Sarcoidosis is a systemic multi-organ granulomatous disease of unknown etiology that is characterized by the presence of granuloma in various organs. The clinical features of sarcoidosis are heterogeneous but pulmonary involvement is cardinal manifestations. The aim of this study was to determine radiologic, clinical and laboratory findings of patients with sarcoidosis.

Patients and Methods:

In a cross-sectional study, all patients visiting sarcoidosis clinic were enrolled in the study. Computed tomography (CT) scan was obtained and lab exams were obtained from patient and reports were recorded in data sheet.

Results:

Total of 55 patients with sarcoidosis were enrolled in the study. The average of age was 44.6 (range 25-62) years. Thirty-seven patients were male and 18 were female. The most common extra-pulmonary manifestation was arthritis (in 18% of cases) and then lupus pernio (12.8%) and uveitis (10.9%). Bilateral hilar adenopathy and para tracheal lymphadenopathy was observed in 39(70%) and 22 (40%) of patients. Parenchymal nodules (30%), bronchiectasia (25%), ground-glass opacification (18%) were the most common findings. Percentages of patients with dyspnea were 29% and percentages of patients with cough were 21%. Among abnormal lab tests, high urine calcium (Ca) were positive in 21% and high angiotensin-converting enzyme (ACE) in 16% of patients.

Conclusion:

Pulmonary involvements are both fibrosis and granulomatosis and the most common manifestations are parenchymal nodules, bronchiectasia and high-grade fibrosis. The most common extra-pulmonary involvement is arthritis. Lab tests are non-specific and have no correlation with duration or severity of disease.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.