A crystalline compound (BM-ANF1) from the Indian toad (Bufo melanostictus, Schneider) skin extract, induced antiproliferation and apoptosis in leukemic and hepatoma cell line involving cell cycle proteins.

In our earlier communication, it was reported that Indian toad (Bufo melanostictus) skin extract (TSE) possesses antiproliferative and apoptogenic activity in U937 and K562 cells [Giri et al., 2006. Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract in U937 and K562 cells. Toxicon 48 (4), 388-400]. In the present study, a compound (BM-ANF1) has been isolated from the TSE by alumina gel column chromatography, crystallized and evaluated for its antiproliferative and apoptogenic activity in U937, K562 and HepG2 cells. BM-ANF1 produced dose-dependent inhibition of U937, K562 and HepG2 cell growth. The antiproliferative activity was reflected by the MTT assay and demonstrated by the reduced expression of proliferative cell nuclear antigen (PCNA). Flow-cytometric analysis showed that BM-ANF1 arrested the cell cycle at G1 phase and enhanced annexin-V binding in U937 and K562 cells. Scanning electron microscopic and fluorescent microscopic analysis of U937 and K562 cells revealed the apoptogenic nature of the compound. Alkaline comet assay showed that BM-ANF1 produced DNA fragmentation. The dose-dependent expression of caspase 3 indicated that the apoptogenic properties of BM-ANF1 were mediated through the activation of downstream effector nucleases in the cancer cells. The increased expression of p53 and moderate expression of p21(Cip1)/p27(Kip1) due to BM-ANF1 treatment in HepG2 cells supported that the apoptogenic activity of BM-ANF1 was mediated through p53 tumor-suppressor gene expression followed by the expression of p21(Cip1) and p27(Kip1) and it was likely to be linked with cell cycle arrest at G1 phase in cancer cells. From the present study, it may be suggested that the crystalline compound, BM-ANF1, was antiproliferative and apoptogenic in human leukemic and hepatoma cells.     

Living environment and self assessed morbidity: a questionnaire-based survey

Background  

Health complaints have been reported to be higher among the industrial area residents when compared with reference community.     

Philadelphia positive acute lymphoblastic leukaemia of childhood

On current chemotherapeutic regimens, children with Philadelphia positive acute lymphoblastic leukaemia show a heterogeneous response to treatment. A few respond quickly to treatment and achieve long-term remission. Some fail to achieve remission after induction and the majority respond slowly to treatment. Relapse on treatment is common and remission is sustained in a proportion of cases only after allogeneic stem cell transplantation (allo-SCT). The use of imatinib along with conventional cytoreductive therapy, prior to allo-SCT appears to be the most promising strategy. The future lies in the molecular evaluation of response to treatment and combination targeted chemotherapy.     

Differential expression of procollagen lysine 2-oxoglutarate 5-deoxygenase and matrix metalloproteinase isoforms in hypothyroid rat ovary and disintegration of extracellular matrix

Hypothyroid-induced reproductive malfunction in both the sexes is a common phenomenon of global concern. In an attempt to characterize the differentially expressed genes that might be responsible for these disorders, we have identified a number of clones in hypothyroid rat ovary by subtractive hybridization. One such clone is procollagen lysyl hydroxylase2 (Plod-2), the key enzyme for the first step of collagen biosynthetic pathway, which was down-regulated in hypothyroid condition. We have also demonstrated the reduced expression of other isoforms of Plods, namely Plod-1 and -3 in hypothyroid rat ovary. The current studies are the first of their kind to report that thyroid hormone regulates the Plod gene in rat ovary. Moreover, we have shown the up-regulation of matrix-degrading enzyme(s), matrix metalloproteinase(s) in the hypothyroid rat ovary, whereas the tissue-inhibitory metalloproteinase is down-regulated. Finally, the results of the present studies indicate that in hypothyroid condition, collagen biosynthesis in ovary seems to be disturbed with concomitant enhancement in collagen degradation, resulting in disintegration of overall ovarian structure.     

Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?

BACKGROUND: Birth weight is known to fluctuate with season of birth, however, there is little information about seasonal variation in neonatal anthropometric measures. AIMS: The aim of this study was to examine seasonal fluctuations in birth weight and selected anthropometric measures. STUDY DESIGN AND SUBJECTS: The birth weight of singletons born after at least 37 weeks gestation was extracted from a perinatal register in south-east Queensland (n=350,171). Mean monthly birth weights for this period were examined. Based on a separate birth cohort, principal component analysis was undertaken on neonatal anthropometric measures (n=1233). Seasonality was assessed by (a) spectral analysis of time series data, (b) monthly and seasonal comparison of outcomes. RESULTS: Based on register data, birth weight displayed clear annual periodicity. Birth weight differed significantly when compared by month and season. Infants born in October were the heaviest (3484 g), while May-born infants were the lightest (3459 g; P=0.001). Based on the cohort anthropometric data, three components were identified related to (a) overall size, (b) limb length, and (c) head size and skin-fold thickness. Each of these components displayed significant seasonal variation. In particular, prominent seasonal fluctuations in limb length were identified, with peak limb length associated with winter/spring birth. CONCLUSION: Environmental factors that have regular seasonal fluctuation influence both the size and shape of neonates. Animal experiments suggest that prenatal hypovitaminosis D may underlie greater limb length. Because birth weight and limb length are associated with a broad range of important health outcomes, the seasonal exposures underlying these effects warrant further scrutiny from a public health perspective.     

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.     

Novel variations in the signal peptide region of transforming growth factor beta1 gene in patients with hepatitis: a brief report from India

Genotypic status of the signal peptide region of transforming growth factor beta1 (TGF-beta1) showed a significant difference in C/C-genotype frequency at +29 position (codon 10) between a range of viral hepatitis patients and controls (P = 0.009, OR = 3.15, CI = 1.29-7.678), contributed by those who were infected with hepatitis B virus (HBV) alone or HBV + hepatitis delta virus (HDV) (P = 0.003, OR = 5.0, CI = 1.78-13.97).     

Risk factor analysis in ischaemic stroke: a hospital-based study

Stroke represents a major health burden in our country. Ischaemic stroke has got several risk factors associated with increased chance of atherosclerosis. A small hospital-based study was done to look into the risk factors associated with ischaemic stroke. Forty patients with CT-confirmed cerebral infarction were taken for the study and detailed history and clinical findings were obtained. Investigations like complete haemogram, fasting blood glucose, urea, creatinine, lipid profile, serum Lp(a), homocysteine, fibrinogen, ECG, chest x-ray, echocardiography, MRI/MRA where indicated, were done to identify the risk factors as well. Results indicated that hypertension was the most prevalent (87.5%) risk factor followed by ischaemic heart disease (35%) and diabetes. Dyslipidaemia was also found in a significant number of cases, mostly elevated LDL, low HDL and elevated Lp(a). Fibrinogen and homocysteine were of less significance.