Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red- cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.      

Quantitative evaluation of liver-specific promoters from retroviral vectors after in vivo transduction of hepatocytes

Hepatic gene therapy could be used to treat a number of inherited blood diseases such as hemophilia or thrombophilia. Although liver-directed retroviral transduction can result in long-term gene expression in vivo, the low level of protein production has limited its clinical application. We reasoned that the insertion of liver-specific promoters into retroviral vectors would increase gene expression in vivo. The 347- bp human alpha 1-antitrypsin (hAAT), the 810-bp murine albumin (mAIb), the 490-bp rat phosphoenolpyruvate carboxykinase (rPECK), and the 596- bp rat liver fatty acid binding protein promoters were inserted into a Moloney murine leukemia retroviral backbone containing the hAAT reporter gene. Vectors that produced appropriately sized RNA and hAAT protein in vitro were tested in vivo by transducing regenerating rat livers. Long-term serum expression of the hAAT reporter gene was normalized to retroviral transduction efficiency as determined by using a polymerase chain reaction-based assay of genomic DNA from transduced rat livers. The hAAT, mAIb, and rPEPCK promoters were, respectively, 35- , 8-, and 0.02-fold as strong as the previously studied constitutive Pol-II promoter. We conclude that the hAAT promoter resulted in the highest expression from a retroviral vector and may result in therapeutically significant expression of other clinically significant blood proteins.     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

NEONATAL OUTCOME IN MECONIUM STAINED DELIVERIES — A PROSPECTIVE STUDY

This prospective study analyzes the neonatal outcome in deliveries complicated by meconium stained amniotic fluid. In a study of 1000 live born deliveries, meconium staining of amniotic fluid was seen in 50 (5%) deliveries. Out of these, 20 newborns (40%) developed classical signs of meconium aspiration syndrome and were managed according to a predetermined protocol. Multiparity, term deliveries, use of sedatives in mother, intrauterine growth retardation and prolonged labour were some of the risk factors for development of meconium aspiration syndrome in newborns. This study highlights the need for review of management protocol in newborns after meconium staining of the amniotic fluid, including the use of prophylactic antibiotics.KEY WORDS: Amniotic fluid, Delivery, Meconium aspiration, Respiratory distress syndrome     

Recovery of coal fines from washery and power plant effluents by integrated technique of oil agglomeration and biofilm formation

The possibility of applying an integrated technique of oil agglomeration and biofilm formation for recovery of coal fines from coal washeries and power plants effluents has been explored. Laboratory experiments with simulated slurries of different Indian coal fines demonstrate that vegetable oils are satisfactory agglomerating agents for recovery of most of the coal fines depending on the nature of coal and type of oil. The agglomeration behaviour of coal fines was assessed in terms of % yield, % organic matter recovery and % ash rejections. Maximum 85% agglomerate recovery was obtained in the agglomeration stage. Residual oil concentrations in some cases were found to exceed the permissible limit. Recovery of residual coal fines and reduction in residual oil concentration in the resultant slurry after oil agglomeration have been attempted using biofilm formation. A laboratory scale treatment reactor was put under complete recirculation to facilitate attached microbial growth on coal particles as carrier under aerobic conditions. The influence of various parameters on attached growth and stable biofilm formation were studied. The growth patterns of attached cell in suspension and consumption pattern of carbon substrate (oil) have been investigated. Steady decline in residual substrate concentration in the slurry with corresponding increase in the growth of attached and free cell mass is observed. The growth process was favoured in pH range of 6.5-7.0. The attached growth was found to be expanded in size in due course of time ultimately leading to the formation of stable biofilm in the treatment reactor which was subjected to the influent total suspended solids loading resulting from oil agglomeration step. Performance of the biofilm reactor in terms of % reduction in total suspended solids and residual oil concentration in the influent slurry was assessed in continuous mode. Complete recovery of coal fines and 60% degradation of oil was observed in the final effluent discharged from the treatment reactor.     

Fas分子与肝细胞凋亡

近年来细胞分子生物学领域中的两个重要进展,即细胞凋亡概念的提出和Ｆａｓ分子的分离与鉴定对肝病的研究有重要影响,加深了人们对肝细胞损伤与死亡的认识．１９９３年Ｏｇａｓａｗａｒａｅｔａｌ［１］进行的Ｆａｓ单抗毒性实验证实了Ｆａｓ分子系统在肝细胞凋亡或损伤...