Appearance Of Bilirubin Research Articles

Therapeutic efficacy of S-adenosylmethionine in chronic uranium intoxication in rats

Introduction. Chronic exposure to uranium compounds causes adverse cytotoxic and immunopathological effects in the body. The aim of the work was to evaluate the therapeutic efficacy of S-adenosylmethionine when administered intragastrically with respect to hepato-, nephro- and immunotoxic effects in chronic intoxicationwith uranyl acetate dihydrate (UAD). Materials and methods. Chronic intoxication was modeled by injecting 85 male rats with UAD solution (5.0 mg/kg/day by element) for one month. S-adenosylmethionine was administered to animals at a dose of 72.7 mg/kg for 21 days. Results. In chronic poisoning with UAD, 65% lethality, decrease of liver mass ratios (MR) and increase of renal MR were observed. Decrease in alkaline phosphatase activity, glucose level, lactic acid, number of CD4+ T-lymphocytes, increase in lactate dehydrogenase activity and creatinine level, number of CD8+ T-lymphocytes and apoptotic cell death, formation of catabolic pool of low and medium molecular weight substances (LMSMS) of blood plasma were registered. The results of urine analysis revealed the development of hyposthenuria, signs of glucosuria, hematosuria, proteinuria and leukocyturia, appearance of bilirubin in the urine. S-adenosylmethionine contributed to the decrease in the degree of target organ damage (reduction of fibroplastic and dystrophic changes in the liver and kidneys), normalization of immune system parameters (increase in CD4+ T-cells, decrease in CD8+ T-cells and frequency of apoptotic death of lymphocytes in immunocompromised animals) and endotoxicosis (decrease in the level of LMSMS from the catabolic pool area). Discussion. According to the totality of all revealed pathological changes, UAD poisoning led to the development of tubulointerstitial nephritis, metabolic disorders of detoxification functions of the liver. The causes of animal death during the first week of the experiment were acute kidney damage or confluent pneumonia. The appearance of bilirubin in the urine was associated with porphyrin metabolism disorders. In the remote period of intoxication an imbalance of the T-cell link of the immune system developed, as well as, probably, a decrease in nonspecific resistance, which led to the development of pneumonia in rats. Conclusion. S-adenosylmethionine therapy of hepato-, nephro- and immunotoxic effects in chronic UAD intoxication contributed to a decrease in the degree of damage to target organs, normalization of immune system parameters and endogenous intoxication.

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.

An acute haemolytic transfusion reaction caused by anti‐Wra

The Wright (Wr(a)) antigen is found on the red blood cells of approximately 1 : 1000 Caucasians. Anti-Wr(a) has been reported to be present in 1 : 25 to 1 : 100 healthy blood donors and an even higher proportion of hospital patients. Incompatibility due to anti-Wr(a) might therefore be expected to occur in approximately 1 in 50,000 blood transfusions. Reports of haemolytic transfusion reactions (HTR) and haemolytic disease of the newborn due to anti-Wr(a) are, however, rare. We report an acute HTR due to anti-Wr(a) in a 58-year-old man with myelodysplastic syndrome associated with rigors, shortness of breath and a significant rise in serum bilirubin from 16 micromol L(-1) pretransfusion to 110 micromol L(-1) immediately afterwards. This was accompanied by the appearance of bilirubin and urobilinogen in his urine and a fall in haemoglobin of nearly 2 g dL(-1) following the transfusion. Anti-Wr(a) was the only antibody implicated. When tested against the recipients plasma, Wr(a+) panel cells and the transfused unit responsible for the reaction were 2-3+ by indirect antiglobulin test (IAT) and the donation typed as Wr(a+). The recipient had the common Wr(a-) phenotype. The reaction resulted in the patient being admitted to hospital for 2 days. The increasing use of electronic issue may result in more frequent reports of reactions due to anti-Wr(a) using current screening cells.

P38 An Acute Hemolytic Transfusion Reaction Due to Anti‐Wra Antibodies.

The Wra antigen is found on the red blood cells of approximately 1 : 1000 caucasians. Anti‐Wra antibodies have been reported to be present in 1 : 25 to 1 : 100 healthy blood donors and an even higher proportion of hospital patients. Wra incompatibilty might therefore be expected to occur in approximately one in 50,000 blood transfusions. Reports of hemolytic transfusion reactions (HTR) and hemolytic disease of the newborn (HDN) due to anti‐Wra are however rare. We report an acute HTR due to anti‐ Wra in a 58 year old male with MDS associated with rigors, shortness of breath and a significant rise in serum bilirubin from 16 μmol L−1 pre‐transfusion to 110 μmol L−1 immediately afterwards. This was accompanied by the appearance of bilirubin and urobilinogen in his urine and a fall in haemoglobin of nearly 2 g dL−1 following the transfusion. Anti‐ Wra was the only antibody implicated. Wra antigen expressing reference panel cells and the unit being transfused during the gave 2–3+ reactions by IAT against the recipient's plasma. The donation typed as positive with Wra antisera. The recipient typed as Wra antigen negative. The reaction resulted in the patient being admitted to hospital for 2 days. The increasing use of electronic issue may result in more frequent reports of reactions due to anti‐Wra as commonly used screening cells do not express this antigen.

皮下組織内胆汁色素生成過程に関する組織顕微分光学的研究

The formation of bilirubin with the absorption maximum at 478-480 mμ from verdohemoglobin could be scarecely decided, because the mixture of decompostion from the oxyhemoglobin produced by the subcutaneous injection of verdohemoglobin to white rat.2. The appearance of bilirubin was observed at the relatively early period on the administration of biliverdin to white rat and the apperance of relatively numerous hematodin crystal was observed.3. On the subcutaneous administration of hematoidin to white rat, it elapsed the product displaying the absorption maximum at 630 mμ and resolved to bilirubin without the formation of methemalbumin.

SOME NEWER CONCEPTS OF THE NATURAL DERIVATIVES OF HEMOGLOBIN: I. General Considerations II. The Serum Bilirubin and Bilirubinuria III. The Erythrocyte Protoporphyrin

Abstract The transition of hemoglobin to bile pigment, at least under normal conditions, is believed to occur via an intermediate biliverdin-globin-iron (verdohemoglobin) and not over the stages of hematin and protoporphyrin. It is probable that the next step is a reduction to bilirubin with splitting off of iron. There is much reason to believe that the globin remains attached until the bilirubin passes through the liver cell, bilirubinglobin exhibiting a delayed or indirect van den Bergh reaction and not being excreted in the urine; the sodium bilirubinate of the bile exhibiting a prompt (1') van den Bergh reaction and being readily excreted in the urine. The former type is characteristic of retention, the latter of regurgitation jaundice. The appearance of bilirubin in the urine is believed to be related to the concentration in the blood of the 1' or prompt bilirubin, rather than that of the total bilirubin. It is evident that the threshold may be considerably lower at the onset of jaundice, as, for example, in hepatitis, than during its defervescence. This undoubtedly accounts for the appearance of bilirubinuria prior to recognizable jaundice in certain instances, likewise for its presence in the cases of so-called "hepatitis without jaundice." In retention jaundice marked elevation of the total serum bilirubin is unassociated with bilirubinuria; in these cases the increase of bilirubin is mainly of the delayed or indirect reacting type. Further evidence is presented of the essential difference between the 1' or prompt, and the T minus 1', or delayed and indirect reacting bilirubins. This consists of a change of the order of reaction at one minute after adding the diazonium salt. The normal upper limit of the 1' bilirubin has been shown to be in the neighborhood of 0.2. mg. per 100 cc.; figures well below this value are usually obtained. Further experience with the erythrocyte protoporphyrin in the anemias has revealed that this determination, quite apart from its fundamental interest, is at times of diagnostic value. Thus in several instances a significant elevation of the erythrocyte protoporphyrin has indicated that the initial impression of pernicious anemia was incorrect, and has led to the search for other information. Conversely, a low normal value in the presence of anemia has often correctly indicated or confirmed the diagnosis of pernicious anemia. Marked elevations have aided in confirming the presence of iron deficiency and have given some insight into the degree of its severity and chronicity. In certain cases, high values for the erythrocyte protoporphyrin have suggested the possibility of heavy metal toxicity, the existence of which has then been borne out by subsequent study.

Bilirubin Resorption in Obstructive Jaundice

SummaryBilirubin did not appear in the blood or thoracic duct lymph when the intrabiliary pressure was lower than the secretory pressure of the liver. Obstruction of the common duct by raising the intrabiliary pressure above the secretory pressure of the liver resulted in bilirubinemia of approximately constant level, and in the appearance of bilirubin in the lymph in concentrations which increased as the intrabiliary pressure was increased.