EFFECT OF LIGHT EXPOSURE ON GUT TRANSIT TIME IN JAUNDICED NEWBORNS

In order to elucidate the mechanism by which phototherapy induces loose stools in newborns, studies were performed on the speed of gut transit by performing the Carmine Red test on normal newborn, on jaundiced newborns before and after phototherapy. A statistically accelerated intestinal transit was observed in jaundiced newborns treated with phototherapy. The increased rate of intestinal transit produced by phototherapy is probably due to the action of the photo-decomposition derivatives of bilirubin, which are excreted during phototherapy.     

A Clinical Study on the Effect of Jinshisan(金石散）in Dissolving Gallstone

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D-PENICILLAMINE, A NON-BILIRUBIN-DISPLACING DRUG IN NEONATAL JAUNDICE

Abstract. Brodersen, R., Lakatos, L. and Karmazsin, L. (Institute of Medical Biochemistry, University of Aarhus, Denmark, and Pediatric Clinic, University Medical School, Debrecen, Hungary). D-penicillamine, a non-bilirubin-displacing drug in neonatal jaundice. Acta Paediatr Scand, 69:31, 1980.—D-penicillamine, a drug used clinically for the treatment of neonatal hyperbilirubinaemia, was tested for interference with the binding of bilirubin to human serum albumin by three methods: 1) The peroxidase technique, investigating the effect of D-penicillamine on the equilibrium concentration of unbound bilirubin in a solution containing a molar excess of albumin; 2) the MADDS method, measuring the concentration of vacant bilirubin binding site on albumin in a solution of pure albumin, or infant blood serum, with added D-penicillamine; and 3) injection of D-penicillamine into Gunn rats and determination of any decrease of plasma biiirubin which would be caused by displacement of the pigment. Results were negative in all cases. Quantitatively, the doses of D-penicillamine used clinically cannot displace bilirubin from its binding to albumin. The ameliorating effect on hyperbilirubinaemia in the newborn must be due to some other mechanism     

EFFECTS OF STABILIZERS IN PREPARATIONS OF HUMAN SERUM ALBUMIN ON THE SERUM BILIRUBIN IN GUNN RATS

ABSTRACT. Commercially available preparations of human serum albumin (HSA) containing stabilizers (i.e. 16 mmol/I Na caprylate plus 16 mmol/I Na N-acetyl- dl -tryptophan) were injected either s.c., i.p. or i.v. into homozygous infant Gunn rats. 30 min and 3 hours after s.c. injection, a serum bilirubin decline which surpassed dilution by the injected volume could be ascertained. It was mainly caused by N-acetyl- dl -tryptophan since s.c. injections of appropriate amounts of this substance alone or a mixture of both components of the stabilizer without HSA brought about similar results. HSA without these stabilizers had not such an effect. It is postulated that under these conditions Na N-acetyl- dl -tryptophanate displaced bilirubin from albumin bonds. It became obvious that after s.c. injection equilibration of HSA between skin and plasma was delayed, whereas Na N-acetyl- dl -tryptophan was rapidly transported to the blood. As for Na caprylate, a displacing effect of short duration could not be excluded by the experimental arrangement used, since the metabolism of the substance in the rat is very fast. When HSA and the stabilizers entered the plasma simultaneously (i.v. injection) no effect on serum bilirubin concentration could be proved 30 min and 3 hours later. All the bilirubin and the Na N-acetyl- dl -tryptophan present in the plasma at that time can be bound to the large amount of albumin which is directly given into the circulation of the animal. 30 min after i.p. injection of HSA preparations containing stabilizers a small decrease of serum bilirubin concentration could be recognized. It was less pronounced and less persisting than after s.c. injection. Probably equilibration of HSA between peritoneum and plasma went on faster than between skin and plasma. Only for a short period a lack of albumin binding sites in the plasma of the rat pointed to a surplus of Na N-acetyl- dl -tryptophan.     

Bilirubin-induced cell death during continuous and intermittent phototherapy and in the dark

AIM: To compare continuous and intermittent light exposure in the presence of bilirubin with respect to cellular damage. Furthermore, it was of interest to characterize the nature of cellular toxicity of bilirubin in the dark. METHOD: A murine lymphoma cell line, L5178Y-R (LY-R), was exposed to solutions of bilirubin (160 microM) supplemented with human serum albumin (200 microM) and irradiated with phototherapy light (Philips 20W/52) at a constant total dose of approximately 500 kJ/m2. The irradiation was given either as intermittent or continuous treatment with light of variable irradiance. The three lower irradiance levels were clinically relevant. Cells treated with bilirubin were also kept in the dark for various periods of time. Cell toxicity was determined by measuring apoptosis and necrosis. Apoptosis was measured by terminal deoxynucleotide transferase and propidium iodide staining assay, while trypan blue assay was used for detection of necrosis. RESULTS: There was no difference (n = 6, p > 0.05) between continuous and intermittent irradiation in the induction of early and late apoptotic cell death. Necrosis was more pronounced after intermittent treatment. Bilirubin dark toxicity was observed and classified as both apoptotic and necrotic. CONCLUSION: Continuous and intermittent light exposure caused the same degree of apoptotic cell death, while the cells underwent more necrotic death after intermittent exposure. Bilirubin was cytotoxic in the dark by both cell death mechanisms.     

Deproteinization of serum: another best approach to eliminate all forms of bilirubin interference on serum creatinine by the kinetic Jaffe reaction

The negative interference of conjugated, unconjugated, and delta bilirubin on patient serum creatinine determined by the kinetic Jaffe reaction is the unresolved problem. We compared bilirubin interference on thirty patients' serum creatinine obtained from four analyzers, with and without deprotenization before the Jaffe reaction, to the Vitros dry enzymatic method. We found significant negative interference from bilirubin on serum creatinine in all samples directly applied to four wet chemical methods, except the one incorporated with serum blank rate. The negative interferences linearly related to bilirubin concentration. However, bilirubin did not interfere on serum creatinine obtained from all wet chemical methods incorporated with deproteinization process before the reaction. We conclude that deproteinized serum before the reaction is the best approach to eliminate all forms of bilirubin interference on serum creatinine determined by the kinetic Jaffe reaction.     

Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic cycling of bilirubin in hamsters

BACKGROUND: We have evidence for enterohepatic cycling of bilirubin experimentally and in vivo in humans. This study was designed to investigate whether Zn salts might inhibit such cycling of bilirubin. MATERIALS AND METHODS: Micellar bile salt solutions with unconjugated bilirubin were prepared, appropriate concentrations of Zn salts were added, and unconjugated bilirubin precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored. RESULTS: Unconjugated bilirubin was precipitated maximally (90%) after a 10-min incubation with 5 mM Zn salts in the pH range of 6.8-9.0. In control hamsters, total bilirubin secretion rates into bile were 36.0 +/- 2.8 nmol h(-1) 100g(-1) body weight, whereas they were 25.0 +/- 3.3 nmol h-1 100(-1) g in the ZnSO4 group (P < 0.05). CONCLUSIONS: Zn salts that flocculate at physiological pH adsorb unconjugated bilirubin almost completely from unsaturated micellar BS solutions. In addition, Zn salts administered orally suppress biliary bilirubin secretion rates in hamsters. These findings suggest that the administration of Zn salts may inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are predisposed to pigment gallstone formation due to diet, disease or drugs.     

综合模拟胆汁体系中未结合胆红素的热力学研究及其临床价值

目的 在Admirand-Small胆汁体系基础上建立-含有未结合胆红素(UCB)的综合模拟体系及其数学模型,并探讨其临床价值。方法 研究胆汁中磷脂、胆盐、胆固醇以及总脂浓度等综合因素对UCB溶解的影响,获得在总脂浓度不一、胆固醇饱和指数(CSI)同时变化的综合模拟胆汁中UCB饱和溶解度的数学表达式,并建立描述UCB致石指数(UCB Lithogenic Index,ULI),评估其临床意义。结果 UCB饱和溶解度值与CSI、磷脂／胆盐 磷脂以及总脂浓度呈有固定的数学关系;临床上胆石症与非胆石症患者胆汁的ULI有显著差异。结论 UCB与胆固醇的溶解、沉淀(热力学)相互影响,考察UCB饱和溶解的指标能判别致石胆汁与非致石胆汁。     

2型糖尿病患者血清总胆红素浓度与总胆固醇关系的探讨

目的 :探讨糖尿病人群中 ,血清总胆红素 (TBIL)水平与总胆固醇 (TCH)的关系。方法 :比较 2 15例男性 2型糖尿病患者 TCH与 TBIL的相关性。结果 :血清总胆固醇与血清总胆红素、结合胆红素呈负相关 (P<0 .0 1)。以 TCH为应变量 ,以与动脉粥样硬化有关的指标为自变量进行多元线性逐步回归分析。结果显示 ,在 P<0 .0 5水平 ,TBIL 继糖化血红蛋白、体重指数后进入模型。结论 :在糖尿病人群中 ,血清总胆红素浓度、总胆固醇存在显著负相关 ,提示低TBIL 可能是导致血脂紊乱的独立危险因素