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排序方式: 共有476条查询结果,搜索用时 921 毫秒
361.
Kevin E. Bove James E. Heubi William F. Balistreri Kenneth D.R. Setchell 《Pediatric and developmental pathology》2004,7(4):315-334
Bile acid synthetic defects (BASD), uncommon genetic disorders that are responsible for approximately 2% of persistent cholestasis in infants, are reviewed with emphasis on morphology of associated liver disease. The associated liver diseases may be life threatening, and are treatable, usually by replacement of deficient primary bile acids. Specific diagnosis is made by analysis of body fluids (bile, blood, and urine) using fast atom bombardment-mass spectroscopy (FAB-MS) and gas chromatography-mass spectroscopy (GC-MS). Inborn errors have been demonstrated for four single enzymes involved in modification of the sterol nucleus and in five steps in modification of the side-chain to form cholic and chenodeoxycholic acids, the primary bile acids.
With few exceptions, BASD cause liver diseases that vary from severe to mild depending on the defect. In three of four known defects of sterol nucleus modification, liver disease is progressive. Progression of liver disease is most rapid when the defect results in accumulation of toxic monohydroxy and unsaturated oxo-bile acids. Liver disease may be transient, delayed in onset and mild. Reduced bile flow caused by atypical bile acids contributes to cholestasis and may be the dominant factor in defects of side-chain synthesis, peroxisomal abiogenesis and S-L-O syndrome. Pathological findings may include intralobular cholestasis with giant cell transformation, prevalence of necrotic hepatocytes including giant cell forms, and hepatitic injury confined to the portal limiting plate where the smallest bile ductules may be injured and where fibrosis typically develops. Interlobular bile ducts are usually spared. Ultrastructure of liver reveals nonspecific changes with the possible exception of unusual canalicular morphology in some defects. The course of BASD may be modified by replacement of deficient primary bile acids, which produces beneficial feedback inhibition of abnormal bile acid production and enhances choluresis.
Giant cell transformation is present in all symptomatic infants with BASD and seems to have a more consistent association with BASD than with the many other liver diseases in infants where it occurs. We hypothesize that immature hepatocytes of infants may fuse to form multinucleate hepatocytes whenever atypical or toxic bile acids are present and the pool of normal bile acids is critically reduced.
This review was supported by NCRR, NIH grant RR-08084. 相似文献
362.
Altered sexually dimorphic nucleus of the preoptic area (SDN-POA) volume in adult Long-Evans rats by dietary soy phytoestrogens 总被引:6,自引:0,他引:6
Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets can alter morphology and physiology in rodents. Phytoestrogens have the ability to bind estrogen receptors and exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body and prostate weight, circulating testosterone and estradiol levels, puberty onset, vaginal cyclicity, and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in Long-Evans rats. Using different experimental protocols, animals were fed either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet. Animals fed the Phyto-600 diet displayed significantly decreased body weights (in males and females), prostate weights and delayed puberty in females compared to that of animals fed the Phyto-free diet. Circulating testosterone or estradiol levels in males or estrous cyclicity were not altered by the diets. The volume of the SDN-POA was significantly altered by a change in diet at 80 days of age where one-half of the males or females fed the Phyto-600 diet (from birth) were switched to the Phyto-free diet until 120 days of age. Males initially fed a Phyto-600 diet but changed to a Phyto-free diet had significantly smaller SDN-POA volumes compared to males fed the Phyto-600 diet (long-term). These data suggest that consumption of phytoestrogens via a soy diet, significantly: (1) decreases body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA volumes during adulthood. 相似文献
363.
J.?M.?DonovanEmail author K.?Von Bergmann K.?D.?R.?Setchell J.?Isaacsohn A.?S.?Pappu D.?R.?Illingworth T.?Olson S.?K.?Burke 《Digestive diseases and sciences》2005,50(7):1-1238
Colesevelam HCl is a potent bile acid–binding polymer. This study's aim was to determine effects of colesevelam HCl on sterol
and bile acid excretion in patients with type IIa hypercholesterolemia. Twenty-four patients (low-density lipoprotein cholesterol,
130 to 220 mg/dL) enrolled in an open-label, parallel-design study, entered an American Heart Association/National Cholesterol
Education Program diet for 6 weeks and were randomized to colesevelam HCl, 2.3 or 3.8 g/day for 4 weeks. In an apparent dose-related
manner, respective mean serum concentrations HCl of low-density lipoprotein cholesterol decreased by 10% (P < 0.01) and 13% (P = 0.05), mean total cholesterol levels decreased by 4.9% (P = 0.05) and 6.1% (P = 0.09), and total fecal bile acid excretion showed median changes of +324% (P < 0.05) and +316% (P < 0.05). Colesevelam HCl did not affect fecal neutral sterol or fecal fatty acid excretion; however, 24-hr urinary mevalonic
acid levels significantly increased in both treatment groups (P < 0.05). The cholesterol-lowering action of colesevelam HCl appears to be mediated through increased bile acid excretion.
The authors acknowledge the Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, USA. This publication was supported
by Sankyo Pharma Inc.
An erratum to this article can be found at 相似文献
364.
365.
Taylor A Sharma M Tsirkas P Di Spiezio Sardo A Setchell M Magos A 《BJOG : an international journal of obstetrics and gynaecology》2005,112(3):340-345
OBJECTIVES: To evaluate triple tourniquets in controlled conditions and for the first time to investigate the hypothesis that leaving a semi-permanent tourniquet around the uterine artery reduces post-operative bleeding from the uterine incisions. DESIGN: A randomised controlled trial. SETTING: Two University teaching hospitals. POPULATION: Twenty-eight patients with symptomatic fibroids and uterine sizes ranging from 14 to 24 weeks of gestation undergoing open myomectomy. METHODS: A number 1 polyglactin suture was tied around the cervix to occlude the uterine arteries, and polythene tourniquets were tied around the infundibulopelvic ligament to obstruct the ovarian vessels. At the end of the procedure, the ovarian ties were released but the uterine artery suture remained in situ. MAIN OUTCOME MEASURES: Intra-operative blood loss, post-operative blood loss, blood transfusion rates, operative morbidity, uterine blood flow and ovarian function. RESULTS: There was significantly less blood lost in the tourniquet group than in the control group (difference between means 1870 mL, 95% CI 1159-2580 mL, P < 0.0001; transfusion rates of 7% and 79%, P= 0.0003). The volume in the pelvic drain 20 min post-operatively and after 48 hours failed to reach statistical significance between the two groups (P= 0.10 and P= 0.165). There were no differences in uterine artery Doppler resistance indices at five days (P= 0.54), six weeks (P= 0.47), three months (P= 0.49) and at six months (P= 0.18). Day two serum FSH concentrations after surgery were unchanged (P= 0.45), compared with baseline values. CONCLUSIONS: Triple tourniquets are effective in reducing bleeding and transfusion rates. There appears no obvious adverse effect on uterine perfusion or ovarian function. 相似文献
366.
Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia 总被引:13,自引:0,他引:13
A rat T-cell leukemia model was used to study the safety of germ cell transplantation as a mean of preventing infertility in males undergoing gonadotoxic cancer treatment. Donor germ cells were harvested from the testes of terminally ill leukemic rats and were either used directly or cryopreserved and thawed before transplantation by rete testis microinjection. All rats transplanted with testicular cells from leukemic donors developed signs of terminal rat T-cell leukemia, whereas control animals remained healthy. Cryopreservation of the donor germ cells caused a 3- to 6-day delay in the terminal phase of leukemia. When a known number of leukemic cells were mixed with germ cells and microinjected into the testis, the rate of appearance of terminal leukemia was directly related to the number of transferred leukemic lymphoblasts. As few as 20 leukemic cells were able to cause a cancer relapse resulting in terminal leukemia 21 days after transplantation in three of five transplanted animals. Our results demonstrate that germ cell transplantation with the presently used techniques is not safe enough for clinical use. Improved methods for purging testicular specimens of cancer cells or totally new approaches with transient xenogenetic host models to detect contamination of malignant cells must be developed before this technique can be offered to patients without fear of disease relapse. 相似文献
367.
Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease 总被引:3,自引:0,他引:3
Heubi JE Wiechmann DA Creutzinger V Setchell KD Squires R Couser R Rhodes P 《The Journal of pediatrics》2002,141(2):237-242
OBJECTIVE: To determine whether tauroursodeoxycholic acid (TUDCA) would prevent or ameliorate the liver injury in neonates treated with total parenteral nutrition (TPN). STUDY DESIGN: Eligible infants were enrolled after surgery when serum direct bilirubin (DB) was <2 mg/dL. TUDCA (30 mg/kg/day) was given enterally to 22 subjects. A concurrent untreated/placebo group was evaluated for comparison (n = 30). Blood chemistries including alanine aminotransferase (ALT), alkaline phosphatase (AP), conjugated bilirubin (CB), and bile acids (BA) were obtained weekly. RESULTS: There was no difference in peak serum CB, ALT, AP, or BA levels between the TUDCA-treated and control infants. When stratified for birth weight (<1500 g and >1500 g), no differences in peak CB, ALT, AP, or BA were noted. Serum CB levels were similar between TUDCA-treated and control infants after 14, 40, 60, 70, and 120 days of TPN. CONCLUSION: TUDCA appears ineffective in preventing the development or treatment of TPN-associated cholestasis in neonates. Erratic biliary enrichment and prolonged inability to initiate treatment may compromise the utility of enterically administered TUDCA for TPN-treated infants. 相似文献
368.
The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones 总被引:20,自引:0,他引:20
Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial metabolism of dietary isoflavones and it possesses estrogenic activity, having affinity for both estrogen receptors, ERalpha and ERbeta. Equol is superior to all other isoflavones in its antioxidant activity. It is the end product of the biotransformation of the phytoestrogen daidzein, one of the two main isoflavones found in abundance in soybeans and most soy foods. Once formed, it is relatively stable; however, equol is not produced in all healthy adults in response to dietary challenge with soy or daidzein. Several recent dietary intervention studies examining the health effects of soy isoflavones allude to the potential importance of equol by establishing that maximal clinical responses to soy protein diets are observed in people who are good "equol-producers." It is now apparent that there are two distinct subpopulations of people and that "bacterio-typing" individuals for their ability to make equol may hold the clue to the effectiveness of soy protein diets in the treatment or prevention of hormone-dependent conditions. In reviewing the history of equol, its biological properties, factors influencing its formation and clinical data, we propose a new paradigm. The clinical effectiveness of soy protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic isoflavone, equol. The failure to distinguish those subjects who are "equol-producers" from "nonequol producers" in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soy. 相似文献
369.
The study was designed to investigate the hyperlipidaemia associated with the steroid responsive nephrotic syndrome in children and in particular to examine the mechanism for the delayed clearance of the circulating triglyceride-rich lipoproteins. The possibility that plasma from patients with steroid responsive nephrotic syndrome may contain an inhibitor of lipoprotein lipase activity was studied by examining the effect of the addition of plasma from patients, on normal postheparin lipoprotein lipase activity. Plasma from children with steroid responsive nephrotic syndrome significantly inhibited lipoprotein lipase activity (p less than 0.001), whereas that from patients with familial hypercholesterolaemia and normal children had no significant effect. The inhibition of lipoprotein lipase activity by plasma from patients with steroid responsive nephrotic syndrome correlated significantly with their increased plasma cholesterol and reduced plasma albumin concentrations (p less than 0.001 and less than 0.02, respectively), but there was no significant correlation with plasma triglyceride concentrations. Thus, the degree of inhibition probably reflected the severity of the condition at the time of study. Neither the cholesterol, albumin nor triglyceride concentrations appeared to directly influence the lipoprotein lipase activity of postheparin plasma. 相似文献
370.
In a programme to examine the effect of 5 months of swimming training on school-children with asthma, 46 children swam a total distance of 3608 km (2242 miles) during 2806 training sessions. On post-training re-examination, nonspecific effects of physical conditioning were detected including improved posture and fitness, reduced fat folds, and enhanced swimming ability. Continuous monitoring of asthma and medication showed significant decreases in both parameters during the final phases of the study between children who continued to swim regularly and those who did not. The frequency and severity of exercise-induced asthma (after running) was unchanged by swimming training. Post-training questionnaires indicated a high degree of enthusiasm and acceptance of the programme by children and parents. No significant adverse effects were observed or reported during the study. 相似文献