Fetal bile acid metabolism: analysis of urinary 3beta-monohydroxy-delta(5) bile acid in preterm infants

To elucidate the urinary concentration of total bile acids after birth and the profile of the usual and unusual urinary bile acids, especially 3beta-hydroxy-5-cholen-24-oic acid (Delta(5)-3beta-ol), we measured the concentrations of 13 bile acids in the urine from preterm infants vs. full-term controls by gas chromatography-mass spectrometry. The urinary concentration of total bile acids in early preterm infants below 32 weeks of gestational age significantly exceeded that of the late preterm and full-term infants (p < 0.0005). The major urinary bile acids in early preterm infants were cholic acid, 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acid and Delta(5)-3beta-ol. In conclusion, the high urinary concentrations of total bile acids in preterm infants may be due to an overproduction, or more likely to a low hepatic bile acid clearance. An alternative fetal pathway, the acidic pathway, may be a major route of bile acid biosynthesis in preterm infants.     

Developmental pattern of urinary bile acid profile in preterm infants

Background:  Bile acid metabolism in preterm infants is yet to be fully characterized. We compared the developmental pattern of urinary bile acid profiles in ten infants born at gestational ages from 25 to 33 weeks with previous data from full-term infants from birth to about 7 months of age.
Methods:  Gas chromatography–mass spectrometry was performed on serial samples.
Results:  Total urinary bile acid concentrations gradually increased until 1 to 2 months of age. After this peak of excretion (30 to 60 µmol/mmol creatinine), total urinary bile acid concentrations gradually decreased to less than 20 µmol/mmol creatinine. The percentage of usual bile acids (mainly cholic acid) relative to total urinary total bile acids gradually deceased from approximately 30% at birth to less than 15% at 7 months of age. On the other hand, 1β-hydroxylated bile acids (mainly 1β,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid) relative to total urinary bile acids were increased gradually from 60% at birth to reach 70% to 80% at 1 month of age. The percentage of 1β-hydroxylated bile acids relative to total urinary bile acids then remained stable at a high percentage (70% to 90%) until the age of 7 months.
Conclusion:  Physiological cholestasis in preterm infants persists longer than in full-term infants. Moreover, as large amounts of cholic and 1β,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acids were detected in urine from preterm infants during this study, the 25-hydroxylation pathway may be particularly important for bile acid synthesis in early preterm infants.     

Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs'negative haemolytic anaemia

We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs'negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum γ-glutamyl transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we detected large amounts of 1β-hydroxylated bile acids, especially lβ,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid (25.5-67.9% of total urine bile acids) in the urine during phenobarbital therapy. However, the amount of urinary 1β-hydroxylated bile acids gradually decreased as the disease progressed. At the end-stage, we detected large amounts of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The ratio of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end-stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of Δ⁴-3-oxo bile acids is increased. Familial intrahepatic cholestasis, Coombs'negative haemolytic anaemia, 1β-hydroxylated bile acids, unsaturated ketonic bile acids     

1 beta-hydroxylated bile acids in the urine of healthy neonates.

In order to clarify the metabolism of bile acids in neonates, 1 beta-hydroxylated bile acids in the urine of healthy newborns were examined by gas chromatography-mass spectrometry. The results showed that the percentage of total 1 beta-hydroxylated bile acids, 3 beta, 12 alpha-dihydroxy-5-cholenoic acid and hyocholic acid in neonates was significantly higher than in older children. The ratio of 1 beta-hydroxylated bile acids to their comparable primary bile acids was also higher in neonates than in older children. These results suggest that 1 beta- and 6 alpha-hydroxylation of bile acids are the predominant pathways of bile acid metabolism in neonates.     

Perinatal bile acid metabolism: analysis of urinary unsaturated ketonic bile acids in preterm and full-term infants

AIM: To compare urinary concentrations of unsaturated ketonic bile acids in preterm and full-term infants. METHODS: Urinary unsaturated ketonic bile acids were determined using gas chromatography-mass spectrometry. RESULTS: Urinary concentrations of total bile acids in early preterm infants (of less than 29wk gestational age) exceeded concentrations in late preterm (between 30 and 37 wk) and full-term infants (between 38 and 41 wk; p < 0.01). The percentage of ketonic bile acids (7alpha, 12alpha-dihydroxy-3-oxo-4-cholenoic acid and 7alpha-hydroxy-3-oxo-4-cholenoic acid) among total urinary bile acids in full-term infants (20.2 +/- 14.1%) was higher than that in early preterm infants (8.94 +/- 8.1%; p < 0.05). The percentage of unsaturated bile acids (3beta-hydroxy-delta5-bile acids) among total bile acids in urine did not differ greatly between groups. CONCLUSION: The percentage of 3-oxo-delta4 bile acids among total bile acids in urine gradually increased from early to late preterm infants, while healthy full-term infants excreted large amounts of 3-oxo-delta4 bile acids in urine at delivery.     

Bile acid metabolism during development: metabolism of lithocholic acid in human fetal liver

The metabolism of [24-14C]lithocholic acid was studied in the microsomal fraction of fetal human liver homogenates. Fetal livers were obtained at legal abortions performed between wk 14 and 24. Product formation was analyzed by thin-layer chromatography, liquid chromatography, and gas chromatography-mass spectrometry. From wk 14 lithocholic acid was hydroxylated in several positions. Hyodeoxycholic acid (3 alpha,6 alpha-dihydroxy-5 beta-cholanoic) and 1 beta,3 alpha-dihydroxy-5 beta-cholanoic acid were identified among the products. The 3 beta-isomer of the former acid, 6 alpha-hydroxy-3-oxo-5 beta-cholanoic acid and a 2-hydroxylithocholic acid were tentatively identified. Two other metabolites carried a hydroxyl group in an unknown position, one of them probably at an angular methyl group. The highest total conversions per mg of microsomal protein were obtained with preparations from 18 wk fetuses. The results are discussed with particular reference to the role of lithocholic acid in fetal hepatotoxicity.     

Bile acids and bile alcohols in two patients with Zellweger (cerebro-hepato-renal) syndrome

The Zellweger cerebro-hepato-renal syndrome (CHRS) is a rare hereditary disease in which there is a generalized deficiency of peroxisomal function. Liver peroxisomes are important for the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid into cholic acid, and, consequently, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid and metabolites of this bile acid precursor accumulate in serum and bile of patients with CHRS. Little is known about the urinary excretion of bile acids in this disease. Using gas chromatography-mass spectrometry we have analyzed serum bile acids and urinary excretion of bile acids and bile alcohols in two Swiss male CHRS patients. As expected, serum concentrations and urinary excretions of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid and 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid were elevated, which is probably an obligatory finding in CHRS. In addition, the urinary excretion of 1,3,7,12-tetrahydroxy-5 beta-cholanoic acid (a very polar unusual bile acid) was increased (99-1556 nmol/24 h). In contrast, the excretion of the major urinary bile alcohol, 27-nor-5 beta-cholestane-3 alpha, 7 alpha,12 alpha,24,25-pentol was found to be normal. 3 alpha, 7 alpha,12 alpha-Trihydroxy-5 beta-C29-dicarboxylic acid, a metabolite of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid previously believed to be obligatory in CHRS, was found only in one of our patients.     

Bile acid metabolism in infants and children and its implications for hepatobiliary diseases

Jenner and Howard proposed the hypothesis that idiopathic obstructive cholangiopathies might be caused by the toxic effect of bile acids, especially toxic monohydroxy bile acids. The toxic effects of bile acids on the liver has been recognized in various species of experimental animals. The present author and co-workers have studied the effects of the acids in the hepatobiliary system of rats and rabbits and found a descending order of toxicity for various bile acids: chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, deoxycholic acid and cholic acid. We have also studied biles acid metabolism in premature and neonatal infants and demonstrated that the metabolism was particularly primitive. The main bile acids were 3β-hydroxy-5 cholenic and chenodeoxycholic acid which may be relatively toxic in vitro. Also we used the intrinsic bile acid loading test by administering MCT (medium chain triglyceride) milk to differentiate between neonatal hepatitis and congenital biliary atresias.     

Urinary bile alcohol profile in infants with intrahepatic cholestasis: identification of 5beta-cholestane-3alpha,7alpha,24,25-tetrol

Urinary bile acids and bile alcohols were examined in six infants aged between 1 and 6 mo who had intrahepatic cholestasis. Following extraction, hydrolysis and solvolysis, cholanoids were analysed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. The relative ratio of the urinary excretion of bile alcohols to bile acids was very low (0.07-0.22) in three patients with mild to severe cholestasis, whereas the urinary excretion of bile alcohols was 2-4 times greater than that of the total bile acids in three patients with slight cholestasis. The urinary bile alcohol spectrum in infants appears to be quite different from that in adults. Although the major bile alcohol was 27-nor-5beta-cholestane-3alpha,7alpha,12alpha,24 ,25-pentol, comprising more than 50% of total urinary bile alcohols in healthy adults, it accounted for only 35% of total urinary bile alcohols in our patients. In addition, bile alcohols carrying chenodeoxycholic acid type nucleus were detected in our patients by comparison of the retention times and mass spectra with those of authentic standards. The presence of 5beta-cholestane-3alpha,7alpha,24,25-tetrol confirmed for the first time in this study may represent an alternative pathway for chenodeoxycholic acid biosynthesis via a "25-hydroxylation pathway" in early life.     

Abnormal low ratio of cholic acid to chenodeoxycholic acid in a cholestatic infant with severe hypoglycemia

We report a premature infant with severe hypoglycemia (serum glucose: 6 mg/dl) and cholestasis (serum total bile acids: 211.55 mumol/L) caused by hypoplasia of the interlobular bile ducts. This patient had developed intracranial hemorrhage and sepsis while undergoing treatment for hypoglycemia. As a result of endocrine evaluation, we made a diagnosis of idiopathic panhypopituitarism, congenital absence or hypoplasia of the pituitary gland. Moreover, we found abnormal bile acid profiles: The ratio of cholic acid to chenodeoxycholic acid was abnormally low in serum (0.04) and in biliary bile (0.33). However, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid and bile alcohols were not detected. We therefore suspected that the severe cholestasis and abnormal bile acid profiles in the serum and biliary bile in this patient were related to physiologic immaturity of the enterohepatic circulation of bile acids and immaturity of hepatic 12 alpha-hydroxylation.     

Prostaglandin and fatty acid metabolism in patients with extrahepatic biliary atresia

The relationship between essential fatty acid (EFA) deficiency and disturbance of prostaglandin (PG) biosynthesis was studied in children after radical operation for extrahepatic biliary atresia (EBA). In addition, to investigate the method for treatment of postoperative EFA deficiency and disturbance of PG biosynthesis, the serum fatty acid and plasma PG levels were determined before and after supplementation of an EFA-rich powder (38 g of linoleic acid per 100 g of powder) through Suruga II enterostomy. Before administration of the EFA-rich powder, linoleic acid, arachidonic acid, PGE1, and PGF2 alpha levels were significantly lower in both good bile excretion and poor bile excretion groups than in the control group. After administration, linoleic acid and PGE1 levels significantly increased in the good bile excretion group as compared with the preadministration values. These results suggest that the supplementation of EFA-rich powder is an effective treatment for linoleic acid deficiency and disturbance of PGE1 biosynthesis in postoperative EBA patients.     

Effect of Ursodeoxycholic Acid on the Expression of the Hepatocellular Bile Acid Transporters (Ntcp and bsep) in Rats With Estrogen-Induced Cholestasis

OBJECTIVES: Rats with ethinyl estradiol-induced cholestasis have a decreased bile flow and a decreased expression of basolateral and canalicular hepatocyte membrane transporters. The bile acid ursodeoxycholic acid improves bile flow in these animals. The purpose of this study was to examine the effect of ursodeoxycholic acid on the expression of hepatocellular bile acid carriers. METHODS: Rats received either ethinyl estradiol (5 mg.kg body wt. for 10 days) or ethinyl estradiol associated with ursodeoxycholic acid (1% in the diet). A third group of rats received ursodeoxycholic acid alone. Bile flow, bile acid, and glutathione biliary outputs were measured. Messenger RNA levels and protein expression of Na -dependent taurocholate co-transporting polypeptide, and bile salt export pump were determined in basolateral and canalicular membrane preparations by Northern and Western blot analysis. RESULTS: Ursodeoxycholic acid restored bile flow in ethinyl estradiol-treated rats by increasing bile acid secretion. It did not improve glutathione output nor bile acid-independent flow. Na -dependent taurocholate co-transporting polypeptide mRNA and protein were decreased by ethinyl estradiol and not restored by ursodeoxycholic acid. In contrast, canalicular bile salt export pump protein expression was decreased by ethinyl estradiol and fully restored to control levels by ursodeoxycholic acid. CONCLUSIONS: Ursodeoxycholic acid increases bile flow in ethinyl estradiol-treated rats by increasing bile acid secretion. This increase is possibly mediated by a normalization of the expression of the canalicular bile salt export pump.     

Failure of ursodeoxycholic acid to dissolve radiolucent gallstones in patients with cystic fibrosis

Ursodeoxycholic acid has been used widely to dissolve cholesterol gallstones and more recently was shown to improve clinical symptoms and biochemical indices in different chronic liver diseases, including that associated with cystic fibrosis. We treated 10 cystic fibrosis patients (5 males, 5 females, age range 2–22 years) with pancreatic insufficiency and normal liver function with ursodeoxycholic acid 15–20 mg/kg/day. Seven patients had radiolucent gallstones (in 3 cases associated with biliary sludge) and 3 had sludge; all were asymptomatic. Before treatment, the gallbladder was well opacified in oral cholecystogram. The gallbladder was scanned by ultrasound in similar conditions and by the same operator before administration of ursodeoxycholic acid and after a median period of treatment of 16 months (range 11–32 months). During treatment, all patients remained asymptomatic and the relative proportion of ursodeoxycholic acid in duodenal bile increased from 4.7 ± 3.2% at baseline to 34.7 ± 8.6%. Complete or partial dissolution of gallstones was never observed and the maximum diameter of stones increased from a mean of 6.1 ± 3.4 to 8.0 ± 5.3 mm; in one case the development of biliary sludge occurred during bile acid therapy. Sludge disappeared in 1 of the 6 patients who initially had it, while in 2 cases its volume increased. We conclude that ursadeokycholic acid is not effective in most CF patients with gallstones, probably because cholesterol is not the main component of stone or sludge.     

Urinary metabolites of oxidative stress and nitric oxide in preterm and term infants

BACKGROUND: Many neonatal diseases have been associated with oxidative stress and altered nitric oxide status. OBJECTIVE: To determine the effects of clinical interventions on the levels of urinary peroxides, a marker of oxidative stress, and urinary nitrate/nitrites, indices of nitric oxide production and metabolism, in the first 72 h of life in premature infants. METHODS: A single, spot urine sample was collected from 82 premature and 20 healthy term infants within the first 72 h of life. The peroxide levels were quantified using a fluorometric method, and nitrate/nitrite levels were quantified by chemiluminescence. RESULTS: Premature infants had a median peroxide level of 10.0 micromol/mmol creatinine (Cr) (interquartile range 4.8-20.0 micromol/mmol Cr). These values were significantly higher than term infants (median 5.0 micromol/mmol Cr, interquartile range 2.7-10.0 micromol/mmol Cr). Urinary nitrate/nitrite levels were not significantly different between preterm (220.5 micromol/mmol Cr, interquartile range 161-287 micromol/mmol Cr) and healthy term infants (244 micromol/mmol Cr, interquartile range 194-316 micromol/mmol Cr). For urinary peroxides, infants on TPN had significantly higher urinary peroxide levels than infants who were not on TPN at the time of urine collection (p = 0.006). Administration of indomethacin was associated with lower levels of urinary nitrate/nitrites (p = 0.0003). Both effects remained significant after controlling for gestational age, degree of respiratory distress and day of urine collection. CONCLUSION: Monitoring the level of both peroxides and nitrate/nitrite may offer added information about the degree of oxidative stress experienced by a newborn but needs to account for clinical and therapeutic interventions.     

动态持续十二指肠液检查鉴别诊断婴儿期持续性阻塞性黄疸

目的　评价动态持续十二指肠液检查鉴别诊断婴儿肝炎综合征 (Infantilehepatitissyndrome,IHS)与胆道闭锁 (Biliaryatresia,BA)的价值 ,寻求简单、快速、正确的鉴别诊断方法。方法应用婴儿十二指肠引流管和引流技术进行动态十二指肠液检查 ,观察十二指肠液颜色、定量测定十二指肠液胆红素值、γ 谷氨酰转肽酶 (γ GT)活性和胆汁酸定性或定量测定。结果　 5 6 1例婴儿持续性黄疸首次十二指肠液检查 ,在插管后 3～ 8min内获黄色液体 342例 ,持续引流 2 4h获黄色液体 2 1例 ,间接引流 4 8～ 72h获黄色液体 16例。十二指肠液呈淡黄色者 71例 ,十二指肠液呈微黄或白色者 111例 ,经治疗后再次对淡黄色和微黄或白色液体者 182例行十二指肠液检查 ,十二指肠液呈黄色者 91例 ,十二指肠液呈白色者 89例 ,呈微黄者 2例。十二指肠液呈黄色和淡黄色者胆红素定量≥ 8 5 μmol/L ,γ GT >2 0Iu/L ,胆汁酸阳性或定量为 33～ 2 6 0 μmol/L ,十二指肠液无色者胆红素值 0～ 2 μmol/L ,十二指肠液微黄者 2例 ,胆红素分别为 5 .8μmol/L ,胆汁酸阴性 ,γ GT 0～ 5Iu/L。以十二指肠液胆红素≥8 5 μmol/L ,胆汁酸阳性 ,γ GT >2 0Iu/L诊断为IHS 4 70例 ,经随访黄疸完全消退。以十二指肠液 <8 5μmol/L ,胆汁酸阴性 ,γ GT <2     

Fetal bile acids in congenital biliary atresia —production in the liver and clinical significance

The 1-hydroxy bile acids have been said to be fetal bile acids. These bile acids were evaluated in eight patients with congenital biliary atresia (CBA) using gas chromatography-mass spectrometry. At the time of operation 1,3,7,12-tetrahydroxy-5-cholan-24-oic acid (CA-1-ol) and 1,3,7-trihydroxy-5-cholan-24-oic acid (CDCA-1-ol) were 0.46 ± 34 g/ml and 0.72 ± 0.45 g/ml, respectively, which was significantly higher than in the control group. The percentage CA-1-ol of total bile acids showed a tendency to decrease as age advanced. The grade of hepatic fibrosis ranged from F₂ to F₃ and the values and percentages of CA-1-ol and CDCA-1-ol were relatively higher in F₂ than F₃ patients. The percentage of total bile acids gradually increased in patients without sufficient bile flow but fell sharply after Kasai's procedure in the patients with sufficient bile flow. It appears that fetal bile acids are produced in the livers of CBA patients in the same way as in fetal liver, and that production continues in patients without good bile secretion even after Kasai's procedure. These results suggest that these hydroxylases are reactivated in CBA patients.     

���� �μ���֭����������Ӥ����֭�ٻ��Ըβ��е�����

??Objective??To detect the level of fecal primary and secondary bile acids in infants with infantile cholestatic hepatopathy??ICH??and analyze its clinical value. Methods??Thirty infants with ICH were enrolled in this study??who were diagnosed with infantile cholestatic hepatopathy. Thirty infants with good health condition were enrolled as the healthy control group. The fecal samples were collected respectively in the preparatory treatment phase and treatment phase from infants with ICH and from the healthy infants. Bile acids were extracted from infants’ feces and were quantitatively analyzed by liquid chromatography-mass spectroscopy. Results??Among the fecal primary bile acids??the level of cholic acid??chenodeoxycholic and glycochenodeoxycholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group??P??0.016??.The level of fecal cholic acid and chenodeoxycholic acid of ICH treatment group was higher than in the ICH preparatory treatment group??P??0.016??. Among the fecal secondary bile acids??the level of lithocholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group??P??0.016????and the level of ursodeoxycholic acid in the ICH preparatory treatment group was lower than that in the ICH treatment group and healthy control group??P??0.016??. Conclusion??In infants with ICH, the changes of fecal primary bile acids and fecal secondary bile acids have their own characteristics at the early stage of treatment, which may be caused by the short-term treatment, the prognosis of the disease itself and the changes of intestinal function, including intestinal bacteria. Clinical attention should be paid to these changes.     

Ursodeoxycholic acid therapy in children with cholestatic liver disease

The beneficial effect of ursodeoxycholic add have been documented in adults but experience with this agent is limited in the pediatric population. The objective of this study was to evaluate ursodeoxycholic acid treatment in children with cholestatic liver disease. Twenty-four patients with intrahepatic cholestasis (neonatal hepatitis 7, Byler disease 7, idiopathic intrahepatic cholestasis 10) whose ages ranged from 1.5 months to 15 years were treated with ursodeoxycholic acid (15-20 mg/kg/day) for 12 months. Liver biopsy was performed initially on all patients and on 17 at the end of the twelve months. The outcome was evaluated by monitoring clinical and biochemical markers of cholestasis, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol, total serum tasting bile acids and total and conjugated bilirubin at entry and every three months of treatment. Pruritus was ameliorated in all patients; there was complete disappearance of itching in 16.7 percent. There were significant decreases in mean serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and gamma-glutamyl transpeptidase. Liver biopsy specimens showed a significant improvement in the cholestasis but not in fibrosis. No adverse effects of therapy were noted. The improvements in the clinical and biochemical parameters and tolerability of the drug suggest that ursodeoxycholic acid is a safe and effective treatment in children with intrahepatic cholestasis.     

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle. Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3 deficiency whereas the three homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia, normal sexual development and revealed no biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is compatible with an autosomal recessive mode of inheritance, sex dependent.     

新生猪多器官功能障碍综合征模型建立的实验研究

目的：探讨采用盲肠结扎加穿孔(CLP)建立新生猪多器官功能障碍综合征(MODS)模型的方法及实验与临床意义。方法：选用健康长白新生猪14只,随机分成实验组(E组,n=9)和对照组(C组,n=5),实验组施行盲肠结扎加穿孔(CLP)制成MODS动物模型,对照组只行剖腹和盲肠探查术。动态观察两组血清生化指标(ALT,AST,ALB,BUN,Cr,CKMB,lac)及血小板、血气分析(PaO2,PaCO2)的变化,通过光镜观察动物各重要生命器官组织形态学变化。结果：与对照组相比,实验组动物在CLP后血ALT,AST,BUN,Cr,CKMB,lac24h即已开始升高,48～96h明显升高,48h时ALT为83.0±9.3U/L、AST为348.8±132.9U/L、BUN为10.5±2.5mmol/L、Cr为79.2±9.0μmol/L、CKMB为5152.0±1857.8U/L、lac为12.3±4.0mmol/L(P<0.01),96h后开始有所降低,但仍高于0h;ALB24h后开始降低,各时间点均低于对照组,但差异无显著性;血小板24h开始降低,96h与0h比较差异有显著性;PaO2和PaCO248h时实验组与对照组差异有非常显著性(P<0.01);实验组动物死亡率与对照组差异有显著性(P<0.05),MODS的发生率为56%。实验组动物肺、肝、心、肾、胃肠道等器官均有不同程度的病理改变。结论：CLP诱发了新生猪多个器官的功能障碍,该实验可用于新生动物MODS模型的探讨。