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71.
Consequences of elevated homocysteine during embryonic development and possible modes of action 总被引:2,自引:0,他引:2
Elevated maternal homocysteine (Hcys) is a well-established risk factor for embryonic toxicity and the development of congenital defects, particularly neural tube closure defects and neurocristopathies. The mechanisms responsible are unclear but early work has focused on the role of folate metabolism because these defects are greatly reduced by folate supplementation. As a consequence, elevated Hcys is often looked upon as being an indirect consequence of faulty folate metabolism, although more recent studies show Hcys may act directly as a teratogen. Because Hcys is at the crossroads of protein and DNA metabolism, has a propensity to chemically modify proteins directly, can generate free radicals, and even perturb ligand binding to certain receptors, the developmental processes Hcys can potentially disturb are enumerable. But in recent years, investigators have begun identifying cellular and molecular targets for the direct action of Hcys. While elevating Hcys can alter a myriad of basic cellular activities needed for normal development, our current understanding as to the specific etiological mechanisms responsible for congenital defects is very speculative. Here we provide an overview of what is currently known regarding the toxicity and teratogenicity of elevated Hcys during embryonic development, paying particular attention to neural tube and neural crest cell morphogenesis. 相似文献
72.
Hatsukami DK Jensen J Brauer LH Mooney M Schulte S Sofuoglu M Pentel PR 《Pharmacology, biochemistry, and behavior》2003,75(1):1-7
Previous studies have shown that cotinine, a metabolite of nicotine, may antagonize some of the therapeutic effects of nicotine. The mechanisms underlying cotinine's effects are unclear, but cotinine has been observed to increase serotonin levels in the brain. Thus, it is possible that blocking serotonin effects may antagonize the actions of cotinine, thereby reducing its impact on responses to nicotine. This study determined whether granisetron, a 5HT(3) receptor antagonist, would enhance the efficacy of the nicotine patch. Subjects were randomly assigned to one of the three granisetron conditions (N=43 for 2 mg/day; N=43 for 1 mg/day; N=42 for 0 mg/day) and asked to take the assigned medication daily during 15 days of tobacco abstinence. Because we were interested in interactions between cotinine and serotonin, all groups were also treated with a 21-mg nicotine patch. Assessments of withdrawal symptoms were made for 1 week during baseline smoking and several times during the experimental period. There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures. The data do not strongly support the hypothesis that 5HT(3) agonism is the mechanism by which cotinine offsets the effects of nicotine. 相似文献
73.
Bergmann RL Richter R Bergmann KE Plagemann A Brauer M Dudenhausen JW 《Paediatric and perinatal epidemiology》2003,17(3):244-249
To investigate the trend in the prevalence of neonatal macrosomia and to evaluate the influences of potential determinants, key features of 206 308 hospital deliveries (97% of all) in Berlin in the years 1993-99, collected by the Berlin Medical Board, were analysed using SPSS 10.0. After exclusion of multiple births and preterm infants, there was a significant increase over 7 years (P < 0.01) in the prevalence of birthweights >or= 4000 g, maternal age >or= 30 years, height of >or= 165 cm, prepregnancy BMI (body mass index) >or= 26 kg/m2 and pregnancy weight gain> 16 kg, but no substantial trend in the prevalence of recognised diabetes or maternal smoking. The adjusted model (OR [95% CI]) for delivering a newborn >or= 4000 g was statistically significant for post-term delivery (2.56 [2.39, 2.75]), women aged >or= 30 years (1.06 [1.02-1.11]), >or= 165 cm tall (1.94 [1.87,2.01]), multiparae (1.98 [1.91, 2.05]), not smoking in pregnancy (2.03 [1.93, 2.14]), prepregnancy BMI >or= 26 compared with < 20 (4.01 [3.77, 4.26]), pregnancy weight gain >or= 16 kg compared with < 10 kg (3.37.[3.22, 3.53]) and for recognised diabetes (1.85.[1.69, 2.04]). It is speculated that this increase in the prevalence of neonatal macrosomia may contribute to the secular trend of overweight and obesity under affluent living conditions. 相似文献
74.
The concentration-response relationship between daily ambient inhalable particle (particulate matter less than or equal to 10 micro m; PM(10)) concentrations and daily mortality typically shows no evidence of a threshold concentration below which no relationship is observed. However, the power to assess a relationship at very low concentrations of PM(10) has been limited in studies to date. The concentrations of PM(10) and other air pollutants in Vancouver, British Columbia, Canada, from January 1994 through December 1996 were very low: the 50th and 90th percentiles of daily average PM(10) concentrations were 13 and 23 micro g/m(3), respectively, and 27 and 39 ppb, respectively, for 1-hr maximum ozone. Analyses of 3 years of daily pollution (PM(10), ozone, sulfur dioxide, nitrogen dioxide, and carbon monoxide) concentrations and mortality counts showed that the dominant associations were between ozone and total mortality and respiratory and cardiovascular mortality in the summer, and between nitrogen dioxide and total mortality in the winter, although some association with PM(10) may also have been present. We conclude that increases in low concentrations of air pollution are associated with increased daily mortality. These findings may support the notion that no threshold pollutant concentrations are present, but they also raise concern that these effects may not be effects of the measured pollutants themselves, but rather of some other factor(s) present in the air pollution-meteorology mix. 相似文献
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76.
In two litigating patients with histories of severe brain injury (i.e., coma > or =2 days and residual brain imaging abnormalities), noncredible cognitive symptomatology was demonstrated by: (1) "failed" performance on multiple cognitive "effort" tests, (2) noncredible performance on standard neuropsychological instruments, (3) questionable validity of personality inventory profiles, and (4) marked inconsistency in test performance across testing evaluations or marked inconsistency between test scores and activities of daily living documented through surveillance videotapes. Some patients with severe traumatic brain injury show substantial, if not full recovery, and in a litigating context, may feign cognitive symptoms. These cases indicate that tests to verify cognitive effort should be routinely administered to all patients in litigation or who have other motive to feign symptoms, not just patients with mild or questionable brain injury. 相似文献
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80.
Stratakis CA Carney JA Kirschner LS Willenberg HS Brauer S Ehrhart-Bornstein M Bornstein SR 《The Journal of clinical endocrinology and metabolism》1999,84(3):1122-1128
Carney complex (CNC) is characterized by lentiginosis and myxomatosis together with a variety of endocrine, neural crest-derived, and other tumors, including primary pigmented nodular adrenocortical disease (PPNAD). PPNAD is characterized by lipofuscin-containing, autonomously functioning, cortisol-producing nodules surrounded by mostly atrophic adrenocortical and normal adrenomedullary tissue. The nature and origin of the tumors, including the myxomas and PPNAD, are unclear. In this study, seven paraffin-embedded PPNAD tumors, one skin myxoma, and two cell lines (one myxoma and one PPNAD) established from patients with CNC were stained with antisera for synaptophysin (SYN), neuron-specific enolase, chromogranin A, tyrosine hydroxylase, and the neural cell adhesion molecule (NCAM). In addition, one PPNAD specimen and one myxoma were analyzed by electron microscopy. The results showed that chromogranin A and tyrosine hydroxylase stained adrenomedullary tissue, but not the PPNAD nodules or the extranodular adrenal cortex. SYN, neuron-specific enolase, and NCAM also stained the medulla. PPNAD nodules and the PPNAD cell line, but not the extranodular adrenal cortex, stained intensely for SYN. The myxoma cell line, but not normal fibroblasts, stained for SYN and NCAM. Ultrastructural analysis of a PPNAD tumor and a skin myxoma revealed a well developed rough endoplasmic reticulum, prominent mitochondria, and vesicle-like structures dispersed throughout the cytoplasm. We conclude that immunostaining for SYN, a marker protein for neuroendocrine cells, clearly distinguishes PPNAD nodules from surrounding adrenocortical tissue and can be helpful in the detection of small nodules in apparently unaffected cortex. The cells of a cutaneous myxoma were also stained positive by two of the three neuroendocrine markers. Finally, both PPNAD and myxoma cells demonstrated ultrastructural features suggestive of neuroendocrine properties. These results support the previously suggested hypothesis that the genetic mechanism leading to CNC involves genes with a neuroendocrine role. 相似文献