Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians

OBJECTIVE: To assess the maternal sociodemographic, anthropometric, dietary and micronutrient status in apparently healthy pregnant women in order to determine their associations with intrauterine growth retardation (IUGR). DESIGN: Prospective observational study. SETTING: Bangalore City, India. SUBJECTS: A total of 478 women were recruited at 12.9+/-3.3 weeks of gestation and followed up at the first, second and third trimesters of pregnancy and at delivery. The dropout rate was 8.5%. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Birth weight was measured at hospital delivery. RESULTS: The mean birth weight was 2.85+/-0.45 kg. In all, 28.6% of newborns were IUGR. There was a strong inverse relationship between maternal educational level and risk of IUGR. A low body weight at baseline was also associated with a high risk of IUGR. Compared with women in the highest quartile for second trimester weight gain, those in the lowest quartile had a significantly higher adjusted odds ratio (AOR: 3.98; 95% CI: 1.83, 8.65) for IUGR. Women in the lowest tertile for serum vitamin B(12) concentration during each of the three trimesters of pregnancy had significantly higher risk of IUGR (AOR: 5.98, 9.28 and 2.81 for trimesters 1-3, respectively). CONCLUSIONS: The present study demonstrates associations between educational status, maternal weight and gestational weight gain with IUGR. Importantly, in a subsample, there were strong associations of vitamin B(12) status with IUGR, suggesting that better socioeconomic conditions, improved nutritional status and early detection of vitamin B(12) deficiency in pregnancy combined with appropriate interventions are likely to play an important role in reducing IUGR.     

DNA damaging drugs-induced down-regulation of Bcl-2 is essential for induction of apoptosis in high-risk HPV-positive HEp-2 and KB cells

DNA damaging chemotherapeutic agents like carboplatin (Carb) and 5-fluorouracil (5-FU), whose effects are mediated through diverse intracellular targets, induce apoptosis in various cancer cells including human papillomavirus (HPV) positive HEp-2 and KB cells. The present work reports the involvement of Bcl-2 in response to the exposure of HEp-2 and KB cells to Carb or 5-FU. We demonstrate that both these drugs are potent inducers of apoptosis. Apoptosis was preceded by decrease in Bcl-2 protein level accompanied by caspase-9 activation and poly(ADP-ribose) polymerase (PARP) cleavage without altering Bax expression. Further analysis revealed down-regulation of Bcl-2 mRNA as well as protein in drugs treated cells. Ectopic expression of Bcl-2 protected cells against drugs mediated DNA damage-induced apoptosis. Overall, data indicates that genotoxic stress leads to down-regulation of Bcl-2 in HEp-2 and KB cells, which plays a decisive role in the outcome of stress in these cells.     

Poly (ADP-ribose) polymerase (PARP) is essential for sulfur mustard-induced DNA damage repair, but has no role in DNA ligase activation

Concurrent activation of poly (ADP-ribose) polymerase (PARP) and DNA ligase was observed in cultured human epidermal keratinocytes (HEK) exposed to the DNA alkylating compound sulfur mustard (SM), suggesting that DNA ligase activation could be due to its modification by PARP. Using HEK, intracellular 3H-labeled NAD+ (3H-adenine) was metabolically generated and then these cells were exposed to SM (1 mM). DNA ligase I isolated from these cells was not 3H-labeled, indicating that DNA ligase I is not a substrate for (ADP-ribosyl)ation by PARP. In HEK, when PARP was inhibited by 3-amino benzamide (3-AB, 2 mM), SM-activated DNA ligase had a half-life that was four-fold higher than that observed in the absence of 3-AB. These results suggest that DNA repair requires PARP, and that DNA ligase remains activated until DNA damage repair is complete. The results show that in SM-exposed HEK, DNA ligase I is activated by phosphorylation catalysed by DNA-dependent protein kinase (DNA-PK). Therefore, the role of PARP in DNA repair is other than that of DNA ligase I activation. By using the DNA ligase I phosphorylation assay and decreasing PARP chemically as well as by PARP anti-sense mRNA expression in the cells, it was confirmed that PARP does not modify DNA ligase I. In conclusion, it is proposed that PARP is essential for efficient DNA repair; however, PARP participates in DNA repair by altering the chromosomal structure to make the DNA damage site(s) accessible to the repair enzymes.     

Tumor angiogenesis--a potential target in cancer chemoprevention.

Tumor angiogenesis is critically important for the growth of solid tumors as tumors remain in dormant phase for a long time in the absence of the initiation of blood vessel formation. Tumors can grow up to approximately 2mm size without requirement of blood supply as diffusion is sufficient at this level to support the removal of wastes from and supply of nutrients to tumor cells. Therefore, angiogenesis process could be an important target to suppress tumor growth and metastasis. Angiogenesis is required at almost every step of tumor progression and metastasis, and tumor vasculature has been identified as strong prognostic marker for tumor grading. Endothelial cells are the main players of angiogenesis process and could be peculiar target for antiangiogenic therapy because they are non-transformed and easily accessible to achievable concentrations of antiangiogenic agents, and also are unlikely to acquire drug resistance. Several antiangiogenic strategies have been developed to inhibit tumor growth by targeting different components of tumor angiogenesis. Chemopreventive agents have been shown to target and inhibit different aspects and components of angiogenesis process and can be used conveniently as they are mostly non-toxic natural compounds and could be part of our daily diet. However, a risk assessment for the use of antiangiogenic phytochemicals is needed as they can also disrupt normal physiologic angiogenesis such as wound healing and endometrium development processes. This review focuses on how different chemopreventive phytochemicals target various components of angiogenesis, including angiogenic signaling, which usually starts from tumor cells producing angiogenic factors and affecting endothelial cells growth, migration and capillary vessel organization for tumor angiogenesis.     

Paediatric airway endoscopy

OBJECTIVES: To review all paediatric endoscopies performed in a tertiary referral unit over a three-year period. METHODS OF STUDY: Retrospective analysis of case-notes of all paediatric endoscopies performed between May 1993 and June 1996. RESULTS: 333 paediatric airway endoscopies were performed on 146 children, of which 52% were GP referrals and the remainder secondary referrals. 70% were diagnostic endoscopies, 30% therapeutic procedures, with the commonest indication being stridor and respiratory distress (82%). Routine chest radiographs, lateral neck X-rays, and barium swallows were unhelpful in the management of the commoner upper-airway conditions. The commonest findings were laryngomalacia (44%) and subglottic stenosis (22%) and 17% of all cases had multiple airway abnormalities. Tracheotomy was performed on 18.4%, laryngotracheoplasty on 7.5%, and laryngotracheal reconstruction on 2.5%. There were no major complications in this series. CONCLUSIONS: All children with airway symptoms should have a thorough rigid-endoscopic evaluation of their upper and lower airways. Radiology has a limited role in the diagnosis of the more common airway pathologies. These patients need to be assessed and managed in regional centres.     

Section 136 and African/Afro-Caribbean minorities

Social, demographic and clinical information was collected retrospectively on all 99 people referred to a South London hospital in 1986 under Section 136 of the Mental Health Act (1983), this being the last complete year before local changes in the procedure for assessment of Section 136 cases were initiated. An over-representation of Afro-Caribbeans was confirmed and this seemed to be accounted for largely by young men under the age of 30 who with Africans had very high rates of previous Section 136 referral, were more likely to be perceived as threatening, incoherent and disturbed but less clearly diagnosed with a mental illness, and were more likely than the Caucasian sample to be living in stable accommodation. The implications of these results are discussed.     

Cell proliferation in growing cultures of dissociated embryonic mouse brain: macromolecule and ornithine decarboxylase synthesis and regulation by hormones and drugs

Primary cultures of cells dissociated from embryonic mouse brain were demonstrated to be a useful system for studying cell proliferation and its regulation. Ornithine decarboxylase activity was closely correlated with the rate of DNA and RNA synthesis during cell growth, suggesting that the enzyme is as good an indicator of cell proliferation in these cultures as it is in vivo. Both DNA synthesis and ornithine decarboxylase activity were stimulated by insulin. The enzyme was stimulated five- to sixfold by insulin and approximately twofold by butyrate, cis-retinoic acid, and 12-O-tetradecanoylphorbol-13-acetate. No effect on the enzyme activity was observed with triiodothyroinine, hydrocortisone, growth hormone, cyclic AMP, or cyclic GMP.