OBJECTIVETo compare the patterns of respiratory function variations resulting from the classical reflex of blood pressure fall and high blood levels of bile acid, so as to provide evidence for the regulation of respiratory function via bile acids.

METHODSSeventy New Zealand male Rabbits, under general anesthesia with 20% urethane, were subjected to tracheal intubations and carotid artery cannulations via median incisions of the neck. Using a biological signal acquisition system, the changes in the breathing and blood pressure were observed in response to stimulation of the pneumogastric nerves or to ear vein injections of diluted bile acids or the water solutions of 5 dissociated bile acids.

RESULTSStimulation of the pneumogastric nerves and injections of diluted bile acids both lowered the blood pressure without significant differences in the total reaction time (T). However, the total respiratory reaction time of bile acids, RT(bile acids), was 9-10 times longer than the total reaction time of blood pressure T(bile acids) (P<0.001). The peak-peak values of respiratory range RR(bile acids) were higher than that RR(pneumogastric nerves)resulting from the classical reflex (P<0.001). In the interval of RT1(bile acids), the values of RR(bile acids) were significantly higher than those of RR(bile acids) in RT2(bile acids) interval. UDCA produced no significant influence on blood pressure or respiratory function (P<0.05) as the other 4 dissociated bile acid reagents did (P<0.001).

CONCLUSIONHigh blood levels of bile acids not only act through reflex factors but also have direct effects on respiratory function regulation. Under our experimental conditions, UDCA has no effect on blood pressure or respiratory function, but the other 4 dissociated bile acid reagents can all dose-dependently lower blood pressure and significantly affect respiratory function.

Animals ; Bile Acids and Salts ; blood ; Blood Pressure ; Male ; Rabbits ; Reflex ; Respiratory Function Tests ; Vagus Nerve ; physiopathology

Alagille syndrome (ALGS) is an autosomal dominant disease affecting multiple systems including the liver, heart, skeleton, eyes, kidneys and face. This paper reports the clinical and genetic features of an infant with this disease. A 3-month-and-10-day-old female infant was referred to the hospital with jaundiced skin and sclera for 3 months. Physical examination revealed wide forehead and micromandible. A systolic murmur of grade 3-4/6 was heard between the 2th and 3th intercostal spaces on the left side of the sternum. The abdomen was distended, and the liver palpable 3 cm under the right subcostal margin with a medium texture. Serum biochemistry analysis revealed abnormal liver function indices, with markedly elevated bilirubin (predominantly direct bilirubin), total bile acids (TBA) and gamma-glutamyl transpeptidase (GGT). Atrial septal defect and pulmonary stenosis were detected on echocardiography. Next generation sequencing detected entire deletion of the JAG1 gene, and then chromosomal microarray analysis revealed a novel interstitial deletion of 3.0 Mb in size on chr20p12.3p12.2, involving JAG1 gene. The child had special facial features, heart malformations, and cholestasis, and based on the genetic findings, ALGS was definitively diagnosed. Thereafter, symptomatic and supportive treatment was introduced. Thus far, the infant had been followed up till his age of 11 months. The hyperbilirubinemia got improved, but GGT and TBA were persistently elevated, and the long-term outcome needs to be observed. This study extended the JAG1 mutation spectrum, and provided laboratory evidences for the diagnosis and treatment of the patient, and for the genetic counseling and prenatal diagnosis in the family.
Alagille Syndrome ; genetics ; Bile Acids and Salts ; blood ; Child, Preschool ; Chromosome Deletion ; Humans ; Jagged-1 Protein ; genetics ; Male ; gamma-Glutamyltransferase ; blood

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of this study was to investigate the clinical features and VPS33B gene mutations of an infant with ARC syndrome. A 47-day-old female infant was referred to the hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal liver function for 39 days. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined diagnosis. Physical examination showed jaundice of the skin and sclera. Systemic skin was dry with desquamation in the limbs and trunk. There were no positive signs on cardiopulmonary examination. The liver was palpable 2.0 cm under the right subcostal margin. The hips and knees were flexed, and the extension was limited, with low muscular tone in the four limbs. Biochemical analysis demonstrated raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and transaminases, but the γ-glutamyl transpeptidase level was normal. Routine urine test revealed increased glucose as well as red and white blood cells. On genetic analysis, the infant was proved to be homologous for a VPS33B mutation c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome. Symptomatic and supportive therapy was given, but no improvement was observed, and the infant finally died at 3 months and 29 days of life.
Arthrogryposis ; blood ; genetics ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis ; blood ; genetics ; Humans ; Mutation ; Renal Insufficiency ; blood ; genetics ; Vesicular Transport Proteins ; genetics

Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges.
Bile Acids and Salts ; blood ; Cholestasis ; blood ; genetics ; physiopathology ; therapy ; Humans ; Infant ; Liver ; physiopathology ; Male ; Mutation ; Oxidoreductases ; blood ; deficiency ; genetics ; Steroid Metabolism, Inborn Errors ; blood ; genetics ; physiopathology ; therapy

OBJECTIVETo study the risk factors for elevated serum total bile acid (TBA) in preterm infants.

METHODSA retrospective analysis was performed for the clinical data of 216 preterm infants who were admitted to the neonatal intensive care unit. According to the presence or absence of elevated TBA (TBA >24.8 μmol/L), the preterm infants were divided into elevated TBA group with 53 infants and non-elevated TBA group with 163 infants. A univariate analysis and an unconditional multivariate logistic regression analysis were used to investigate the risk factors for elevated TBA.

RESULTSThe univariate analysis showed that there were significant differences between the elevated TBA group and the non-elevated TBA group in gestational age at birth, birth weight, proportion of small-for-gestational-age infants, proportion of infants undergoing ventilator-assisted ventilation, fasting time, parenteral nutrition time, and incidence of neonatal respiratory failure and sepsis (P<0.05). The unconditional multivariate logistic regression analysis showed that low birth weight (OR=3.84, 95%CI: 1.53-9.64) and neonatal sepsis (OR=2.56, 95%CI: 1.01-6.47) were independent risk factors for elevated TBA in preterm infants.

CONCLUSIONSLow birth weight and neonatal sepsis may lead to elevated TBA in preterm infants.

Bile Acids and Salts ; blood ; Female ; Humans ; Infant, Low Birth Weight ; blood ; Infant, Newborn ; Infant, Premature ; blood ; Logistic Models ; Male ; Retrospective Studies ; Risk Factors ; Sepsis ; blood

OBJECTIVETo assess the effects of treatment of Amanita mushroom poisoning with Glossy anoderma Decoction (, GGD).

METHODSTwelve patients with acute Amanita mushroom poisoning received conventional treatment (penicillin and reduced glutathione) combined with oral administration of GGD (treated group), which was prepared out of 200 g Glossy ganoderma decocted in water to 600 mL, and 200 ml was given once, three times a day for 7 successive days; while conventional treatment alone was given to the other 11 patients assigned to the control group. The therapeutic efficacy and changes in serum levels of total bilirubin (TBil), bile acids (BA), alanine transaminase (ALT), and aspartate transaminase (AST) activities in the two groups were compared.

RESULTSThe cured-markedly effective rate in the treated group was more significant than that in the control group (P<0.01). Elevation in TBil, BA, ALT, and AST activities were observed in both groups 3 days after poisoning, which progressively increased thereafter in the control group. In the treated group, they reached their peak on the 3rd day and then declined gradually. The differences between pre-treatment and post-treatment in both groups were obviously significant (P<0.01), so were the differences between the two groups at corresponding time points (P<0.01).

CONCLUSIONGGD shows excellent clinical efficacy in the treatment of acute Amanita mushroom poisoning and can reduce mortality significantly.

Acute Disease ; Adolescent ; Adult ; Amanita ; Bile Acids and Salts ; blood ; Child ; Female ; Ganoderma ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Mushroom Poisoning ; blood ; drug therapy ; mortality

The present study was conducted to evaluate the usefulness of common Korean legumes as a high-fiber supplement in therapeutic diets for diabetic patients. Streptozotocin-induced diabetic rats were used as animal models and four kinds of legumes, black soybean (BS), yellow soybean (YS), green pea (GP) and soybean curd residue (SCR) were tested as high-fiber supplements. Seven groups of normal and streptozotocin-induced diabetic rats were fed isocaloric experimental diets containing 8% dietary fiber from one of four legumes or purified cellulose and pectin for 6 weeks. The effects of the legumes on the glucose and lipid metabolism of diabetic rats was examined and compared with the effects of cellulose and pectin. The legume supplementation did not show any beneficial effect on glucose tolerance, however, it exhibited a plasma cholesterol-lowering effect in diabetic rats. The cholesterol-lowering action was especially strong in BS and the degree of the effect was comparable to that of pectin. The levels of total lipids, cholesterol, and triglyceride in the hepatic tissues of rats fed legume diets were similar to those of the pectin group. All legume supplements induced an increase in fecal steroid excretion. The fecal cholesterol contents were significantly high following the supplementations of YS and SCR (p<0.05). The excretion of fecal bile acids in the BS and YS groups was significantly higher than it was in the pectin group (p<0.05). Concentration of lipid peroxidation products in the blood and urine of diabetic animals was lower in the legume groups than in the cellulose group. The levels of hepatic lipid peroxidation products were significantly lower in the BS and YS groups than in the pectin group (p<0.05). From the results of this study, the plasma cholesterol-lowering effect of BS is possibly due to the significant (p<0.05) in-crease in fecal steroid excretion, which suggests that BS could be beneficial in improving abnormal lipid metabolism in diabetic rats.
Animals ; Bile Acids and Salts ; Blood Glucose ; Cellulose ; Cholesterol ; Diet ; Dietary Fiber ; Fabaceae* ; Glucose* ; Humans ; Lipid Metabolism* ; Lipid Peroxidation* ; Models, Animal ; Peas ; Plasma ; Rats* ; Soybeans ; Triglycerides

Pathophysiological conditions such as sepsis and hepatitis are frequently associated with cholestasis. Cholestasis in patients with sepsis has been attributed to the effects of endotoxin(lipopholysaccharides, LPS) and LPS-induced cytokines(TNF-a, IL-6, IL-1, etc.). LPS and cytokines reduced bile acid uptake in cultured hepatocyte. Perfusion of LPS decrease the bile flow in the isolated liver. Bile flow is increased by intravenous infusion of secretin, but it's effect remains unclear in sepsis. The aim, of this study is to elucidate the effect of LPS on the bile flow and bile composition and to test the effect of secretin on the bile flow. The animals used in this study were Korean wild cats. Under the general anesthesia, the incision was made on the midline. Common bile duct was cannulated with polyethylene tube after cholecystectomy. Bile was collected every five minutes and its volume was measured. E. coli LPS(1 mg/kg), secretin(0.1mg/kg) and H3-taurocholic acid(0.2uCi/kg) were infused via mesenteric vein. Bile was collected every 5 minutes, and the volume and its composition were analyzed. Radio-activity of the bile was quantified by Packard 1600 TR liquid scintillation analyzer. LPS of E.coli (1mg/kg) had a little effect on the blood pressure. LPS decreased the bile flow by 37% compared with the control group. Maximal impairment of the bile secretion appeared 15 minites after LPS infusion, and then secreted stablely thereafter. Secretin increased the bile flow in the normal control group. It, however, did not make any change in the bile flow after LPS infusion. LPS also reduced H3-taurocholate secretion(maximum 56%), and peak level was delayed about 10 minites compared with control group. In the composition of the bile, LPS decreased the secretion of bile acids significantly compared with the control group. Conclusively, LPS decreased the bile flow and the bile acid secretion. Secretin did not stimulate the bile flow in the LPS group. It also reduced the bile acids secretion compared with the control group. These findings will contribute to the understanding and treatment of the cholestasis and impairment of the liver function of sepsis. The findings, of reduced bile acids secretion in the LPS group may explain the pathogenesis of intrahepatic gallstone partly.
Anesthesia, General ; Animals ; Bile Acids and Salts ; Bile* ; Blood Pressure ; Cats* ; Cholecystectomy ; Cholestasis ; Common Bile Duct ; Cytokines ; Escherichia coli* ; Escherichia* ; Gallstones ; Hepatitis ; Hepatocytes ; Humans ; Infusions, Intravenous ; Interleukin-1 ; Interleukin-6 ; Liver ; Mesenteric Veins ; Perfusion ; Polyethylene ; Secretin ; Sepsis

OBJECTIVETo study injury of liver and kidney among the workers exposed to terephthalic acid(TPA), ethylene glycol(EG) and(or) dowtherm A(DOW), and research for early biological monitoring indexes.

METHODSBy using the method of occupational epidemiology, an investigation of industrial hygiene in a chemical fibre corporation was carried out and the changes of the liver and kidney functions were analyzed among the workers who had been exposed to TPA, EG, DOW.

RESULTSThe values of serum gamma-glutamyl traspetidase(GGT) and total bile acid(TBA) in TPA + EG + DOW group men were (35.45 +/- 16.09) U/L, (10.29 +/- 6.76) mumol/L respectively and the values of serum alanine transaminase(ALT) and TBA in TPA + EG + DOW group women were(30.68 +/- 8.58) U/L, (9.53 +/- 6.63) mumol/L respectively, significantly higher than those in TPA, DOW and control groups(P < 0.05, P < 0.01). Compared with TPA, DOW and control groups, the values of urine N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-2-microglobulim (beta 2-MG) in TPA + EG + DOW group of both men and women increased significantly(P < 0.05, P < 0.01), with(5.68 +/- 4.01) U/mmol Cr and (23.49 +/- 13.44) mg/mol Cr, and(6.68 +/- 4.68) U/mmol Cr and (22.80 +/- 13.00) mg/mol Cr, respectively. Analysis of regression indicated that both liver and renal injuries of the workers were evidently correlated with their exposure to TPA, EG and DOW after adjustment for the confounding factors such as sex, smoking, drinking, etc(P < 0.001).

CONCLUSIONBased on available knowledge, it is reasonable to assume that the joint actions should be considered on the injury of liver and kidney caused by TPA, EG and(or) DOW among the workers. Serum ALT, GGT, TBA, urine NAG and beta 2-MG should be suggested as biomarkers for liver and kidney damage.

Acetylglucosaminidase ; urine ; Alanine Transaminase ; blood ; Bile Acids and Salts ; blood ; Ethylene Glycol ; toxicity ; Female ; Humans ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Occupational Exposure ; adverse effects ; Phenyl Ethers ; toxicity ; Phthalic Acids ; toxicity ; gamma-Glutamyltransferase ; blood

OBJECTIVETo explore the effect of cold preservation and reperfusion injury (CPRI) on the bile salt spectrum in rat orthotopic liver transplantation (OLT) model.

METHODSA special analysis method was established to investigate the bile salts in rat by reverse phase high performance liquid chromatography (RP-HPLC). Rats were randomly divided into 3 groups: group A (control group, n = 6), group B (group with 1 h graft preservation pre-OLT, n = 6) and group C (group with 12 h graft preservation pre-OLT, n = 6). The bile samples of 0 - 14 post-transplantation days were analyzed by RP-HPLC.

RESULTSEleven kinds of bile salts were detected in rat bile. It showed that CPRI could influence the concentration of bile salts significantly in rat model after OLT, the concentration of hydrophobic bile salts (TCA and TCDCA) increased significantly in group B and C. However, the concentration of hydrophilic bile salts (TUDCA and THDCA) just increased in a short-time. The hydrophobicity index (HI) wasn't significantly changed during the first 4 post-transplant days. Thus the HI of bile salts elevated gradually from the 5th day and reached the peak at the 10th day after OLT.

CONCLUSIONThe increase of the proportion of hydrophobic bile salts may be one of the major factors leading to the increase of bile toxicity after OLT.

Animals ; Bile ; metabolism ; Bile Acids and Salts ; secretion ; Chromatography, High Pressure Liquid ; Cryopreservation ; Disease Models, Animal ; Liver ; blood supply ; metabolism ; Liver Transplantation ; Male ; Postoperative Period ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology