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J D Ostrow

Publications and source records attributed to J D Ostrow.

At least 73 records · Page 4Linked to original sources

Excretion of administered and endogenous photobilirubins in the bile of the jaundice gunn rat.

Radiolabeled photobilirubins, prepared in vitro by anaerobic illumination of [34C]bilirubin, were injected intravenously into homozygous jaundiced Gunn rats with an external bile fistula. With the animals kept in darkness, the labeled photobilirubins were excreted rapidly in bile. Photobilirubins IA and IB were excreted primarily as unconjugated bilirubin, whereas photobilirubin II was excreted primarily as photobilirubin II and not converted into bilirubin. Bile of Gunn rats given no exogenous pigments, but undergoing phototherapy, contained a large proportion of photobilirubin II and, if collected in liquid nitrogen, traces of photobilirubins I; neither was found in bile when these rats were kept in the dark. Because there is prior evidence that these rats were kept in the dark. Because there is prior evidence that these photobilirubins are isomers of bilirubin, these experiments indicate that the major mechanism of phototherapy is photoisomerization of bilirubin. Photobilirubin II is the unidentified major photoderivative described previously, whereas formation of photobilirubins IA and IB, and their reversion to bilirubin-IXalpha, account for the remarkably increased output of the parent pigment during phototherapy.

Animals↗

New concepts in phototherapy: photoisomerization of bilirubin IX alpha and potential toxic effects of light.

New information is summarized, indicating that configurational photoisomerization of bilirubin at the 5 and 15 carbon bridges is the major mechanism of bilirubin photocatabolism in vivo, and that singlet oxygen photooxidation plays only a minor role. The literature is reviewed concerning potentially damaging photodynamic reactions that are observed in vitro with vitamins, proteins, lipids, and nucleic acids, and their possible relationships to the limited number of toxic side-effects that have been detected with clinical phototherapy of neonatal jaundice. Secondary toxic effects, mediated by bilirubin photoderivatives or by retina-neuroendocrine pathways are also considered. Areas requiring further investigations are delineated.

Bilirubin↗

Preparation and properties of bilirubin photoisomers.

Polar photoisomers of bilirubin were formed by irradiation of bilirubin in chloroform solution in the absence of O2. Two pairs of compounds were isolated with molecular weights identical with bilirubin. One pair reverted to bilirubin in polar media and gave chemical reactions similar to bilirubin; the other pair were not reconverted into bilirubin by chemical means and gave reactions distinct from those of bilirubin. However, both groups were reconverted into bilirubin by irradiation in chloroform solution in the absence of O2. The probable role of these photoisomers in the catabolism of bilirubin during phototherapy of neonatal jaundice is discussed.

Bilirubin↗

Inaccuracies in measurement of conjugated and unconjugated bilirubin in bile with ethyl anthranilate diazo and solvent-partition methods.

A criticial evaluation was made of the ethyl anthranilate diazo and two solvent-partition methods for the determination of conjugated and unconjugated bilirubin in human and rat bile. The ethyl anthranilate diazo reagent, which reacts only with conjugated bilirubin in serum, also diazotized a variable proportion of unconjugated bilirubin in bile and thus overestimated the concentration of monoconjugates. With the Weber-Schalm and modified Folsch solvent-partition methods applied to human or rat bile, 4--9% of added 14C-labelled unconjugated bilirubin partitioned with the conjugated bilirubin in the upper phase, and 4--9% of added 14C-labelled conjugated bilirubin partitioned into the lower phase. With dog bile, the spill-over of 14C-labelled bilirubin into the lower phase was 9--11%. Analysis of azopigments from the Weber-Schalm partition confirmed that over two-thirds of the bilirubin in the lower phase represents monoconjugates, principally the less-polar monoxylosides and monoglucosides. These solvent-partition methods thus overestimate the concentration of unconjugated bilirubin in bile.

Animals↗

Pigment gallstone composition in cirrhotic and noncirrhotic subjects.

The composition of pigment gallstones from patients with and without cirrhosis was compared. Carbonate-containing pigment stones were distinguished from noncarbonate stones by infrared spectroscopy. Calcium was the major cation of each stone group. The major anion in noncarbonate pigment stones was bilirubinate or phosphate, but was carbonate in carbonate stones. The composition of pigment stones from cirrhotic and noncirrhotic patients was similar except that significantly less carbonate was present in carbonate stones, and less pigment (bilirubinate) was present in noncarbonate stones from noncirrhotics. These data suggest that irrespective of the presence of cirrhosis, the formation of noncarbonate pigment stones involves the selective precipitation of calcium bilirubinate and phosphate, whereas carbonate stone formation involves the selective precipitation of calcium carbonate.

Age Factors↗

Stimulation of bilirubin catabolism in jaundiced Gunn rats by an induced of microsomal mixed-function monooxygenases.

The homozygous, jaundiced Gunn rat compensates for its inability to form bilirubin conjugates by production of polar bilirubin metabolites which can be excreted in the bile without conjugation. To assess whether microsomal mixed-function monooxygenases might be involved in formation of these metabolites, a potent inducer of these enzymes, 2,3,7,8-tetrachlorodibenzo-p-dioxin, was administered to Gunn rats in a single intraperitoneal dose of 10 mug/kg. Four to 6 days after treatment, plasma bilirubin levels had declined by a mean of 61%, whereas no significant change was observed in control Gunn rats that received only the dioxane vehicle. Use of tracer [(14)C]bilirubin showed that the decline in plasma bilirubin was the result of a 7-fold increase in fractional bilirubin turnover which reduced the bilirubin pool to an average of 11% of the control values. In the new steady state, total bilirubin turnover was unaltered. The accelerated fractional bilirubin turnover was associated with augmented biliary excretion of polar bilirubin metabolites and a 16-fold increase in hepatic benzo[a]-pyrene hydroxylase activity. Hepatic bilirubin-UDPglucuronate transferase was not induced, and no bilirubin conjugates appeared in the bile. This chemical simulation of the alternate pathways of bilirubin catabolism by the inducer suggests that microsomal cytochrome P(448)-dependent monooxygenases may be involved in the formation of the polar bilirubin metabolites excreted by the Gunn rat.

Animals↗

Pigment gallstones.

Pigment gallstones are defined as any dark brown-to-black stone, consisting of calcium salts of bilirubin, phosphate, carbonate and other anions, and can be separated into carbonate- and noncarbonate-containing groups. Pigment stones predominate in the rural Orient, in cirrhosis, and in elderly United States patients undergoing cholecystectomy. Clinical associations include bile duct obstruction, stasis, and possibly hemolysis. Of pigment stones, 50% are radioopaque and account for two-thirds of all opaque stones. The concentrations of bile salts, phospholipids,, cholesterol, and total bilirubin in bile are similar to normal levels, but the concentration of unconjugated bilirubin is increased in the bile of some patients. Increased unconjugated bilirubin in bile may be caused by increased hydrolysis of excreted conjugated bilirubin. Unconjugated bilirubin is solubilized by bile salts, but the interaction is primarily nonmicellar. Ionized calcium and pH are important determinants of solubility. Sulfated glycoproteins, excreted in increased amounts in patients with cholelithiasis, may be the site of pigment stone precipitation because these compounds bind calcium salts tightly. E coli is frequently cultured from pigment stones in Japan but not in the United States; thus, bacterial beta-glucuronidase may be important in stone formation in Japan but probably not in the West. Stasis leads to increased calcium secretion and to increases in the concentration of sparingly soluble compounds that may then precipitate. Incomplete emptying of the gallbladder may result in the same concentration process. Unsaturated fats and chronic vagal stimulation cause pigment stone formation in animals. At present, surgery is the only treatment for pigment lithiasis.

Adolescent↗

Pigment versus cholesterol cholelithiasis: identification and quantification by infrared spectroscopy.

We previously reported that 27% of 92 cholecystectomized patients had pigment stones (Am J Dig Dis 19:585-590, 1974). Using standard biochemical methods, we found that cholesterol accounted for an average of 77% of the dry weight of cholesterol stones, but that unconjugated bilirubin represented a mean of only 7% of pigment stones. This quantitation of pigment stones was limited because approximately 66% of their weight was insoluble. To characterize pigment and cholesterol stone composition further, we used infrared spectroscopy--a technique requiring neither crystallinity nor solubilization--to quantitate pigment, carbonate, and cholesterol in gallstones. Other organic and inorganic components of stones were measured by standard methods. By infrared spectroscopy, two types of pigment stones were identified: carbonate-containing and noncarbonate pigment stones. Carbonate pigment stones contained significantly more calcium, carbonate, and phosphate, but less pigment than noncarbonate stones. Compared to our initial report, the total measured components of all pigment stones were increased 6-fold from 10 to 63%. Cholesterol was the major component of cholesterol stones by chemical assay or infrared spectroscopy. Among five cholesterol stones with limited solubility, 80% of the insoluble residue was identified as cholesterol by infrared spectroscopy. This study extends our knowledge of pigment stone and cholesterol stone composition by the use of quantitative infrared spectroscopy in conjunction with standard biochemical methods; furthermore, it confirms that pigment and cholesterol stones differ in composition and form by different mechanisms.

Carbonates↗

Hemoccult testing.

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Blood Chemical Analysis↗

Reliability of chemical tests for fecal occult blood in hospitalized patients.

In 39 hospitalized patients with suspected gastrointestinal bleeding and given intravenous 51Cr-labeled red cells, reactions of three chemical spot tests for fecal occult blood were compared with the "true" blood loss as determined by stool radioassay. Guaiac reagent and orthotolidine (Hematest) tablets were extremely sensitive, but yielded false-positive reaction rates of 72% and 76%, respectively on the 240 stool specimens compared. A modified guaiac test (Hemoccult) exhibited a false positive rate of 12%. Of the 27 patients entering the study due to positive guaiac or Hematest screening tests, 17 (63%) were not bleeding. Hemoccult, approximately 1/4 as sensitive as guaiac and Hematest, could miss lesions with low rates of bleeding unless multiple stools were tested. While barium had no effect, iron therapy or laxatives tended to lower both false-positive and false-negative reactions for all reagents. A positive Hemoccult test usually indicated significant gastrointestinal bleeding and would appear to be the test of choice provided at least 3 stools are tested to minimize false-negative results.

Barium Sulfate↗

Effects of phototherapy on hepatic function in human alcoholic cirrhosis.

Phototherapy has been used to treat neonatal jaundice, but little assessment has been made of possible beneficial effects on adult liver disease. Effects of phototherapy on bile acid turnover, biliary lipid concentration, liver function tests, and bromosulfophthalein (BSP) kinetics were studied in 8 alcoholic cirrhotics. Phototherapy initially increased biliary specific activity of both primary bile acids and then produced an acceleration of cholic and chenodeoxycholic acid decay curves. Pruritus was relieved in the 3 patients who had this symptom. The proposed mechanism for these changes is mobilization of bile acids from an expanded cutaneous bile acid pool with augmented bile acid excretion. No significant change in serum liver function tests or BSP plasma disappearance curves was seen. Phototherapy causes little improvement in intrinsic liver function, but produces specific changes in bile acid metabolism; these changes may be related to effects of light on a cutaneous bile acid pool.

Adult↗

Effect of phototherapy on bilirubin excretion in man and the rat.

Further evidence that the bilirubin excreted by Gunn rats during phototherapy is unconjugated is presented. The unconjugated bilirubin is not carried into bile as a water-soluble complex with rapidly excreted bilirubin derivatives, nor as a result of leakage of plasma protein into bile. Phototherapy does not augment biliary excretion of bilirubin in normal nonjaundiced rats, but does increase the concentration of conjugated bilirubin in the bile of patients with alcoholic cirrhosis, although their serum bilirubin concentrations are unaffected. The mechanism for augmented excretion of unconjugated bilirubin during phototherapy remains unexplained.

Alcoholism↗

Measurement of conjugated and unconjugated bilirubin in bile. II. A new thin-layer chromatographic method.

A new thin-layer chromatographic (TLC) method is described for measurement of conjugated (CB) and unconjugated (UCB) bilirubin in bile. Bile is streaked on a silica-gel plate and developed with chloroform. Bilirubin in the mobile UCB band and stationary CB band is quantitated by diazotization from the scraped gel with p-iodoaniline reagent. Both CB and UCB in bile yielded identical azopigment absorbance. There was no contamination of the UBC band with either CB or oxidative derivatives of bilirubin, and over 98 per cent added 14C-UBC migrated with the mobile band. Recoveries from TLC averaged 98.2 +/- 4.3 per cent of the applied pigment, duplicated agreed within 10 per cent, and the method accurately detected the enzymatic and alkaline hydrolysis of CB to UCB. Concentrations of UCB in nine samples of normal human gallbladder bile were found to be less than 1.9 mg./dl. and never exceeded 1.2 per cent of the total bilirubin.

Aniline Compounds↗