Biomedical subjects

J B Watkins

Publications and source records attributed to J B Watkins.

133 records · Page 8Linked to original sources

PubMedDate not supplied

Successful management of an acquired gastric outlet obstruction with endoscopy guided balloon dilatation.

Antral-pyloric strictures and gastric outlet obstruction are known complications of caustic ingestions. These lesions can develop even in the absence of overt signs of potentially serious upper gastrointestinal tract pathology such as oropharyngeal burns, dysphagia, vomiting, or abdominal pain at the time of ingestion. The development of radial balloon catheters, which can be endoscopically guided into narrow strictures and inflated, offers an alternative therapy to surgical resection of obstructing lesions. We report the successful management of a pyloric stricture secondary to a caustic ingestion by sequential endoscopically guided balloon dilatations and offer guidelines for the use of this procedure.

Catheterization↗

PubMedDate not supplied

Comparative study of phase II biotransformation in rabbit ocular tissues.

To assess the biotransformational capability of ocular tissues in the rabbit, representative phase II enzymes were assayed in five tissues from the eye, and in the liver, kidney, and intestine. Within the eye, the iris/ciliary body exhibited the highest glutathione S-transferase activity, whereas the cornea possessed the highest specific activities for N-acetyl-, sulfo-, and UDP-glucuronosyl-transferases. Cornea, iris/ciliary body, choroid, and retina exhibited significant activities of p-aminobenzoic acid N-acetyltransferase, 2-naphthol sulfotransferase, and 1-chloro-2,4-dinitrobenzene glutathione S-transferase. Despite its size and protein content, lens displayed little or no biotransformational activity. Only the iris/ciliary body conjugated sulfobromophthalein with glutathione. UDP-glucuronsyltransferase activity varied depending on tested substrates and tissues. When compared to liver, kidney, or intestine, N-acetyltransferase activity in the iris/ciliary body nearly matched the rate measured in kidney, glutathione S-transferase activity in cornea and iris/ciliary body was nearly 70 and 89%, respectively, of the rate in intestine, and corneal sulfotransferase activity was greater than that in kidney. These data suggest that biotransformation pathways are present in the eye, and particularly in ocular tissues having adequate blood supply or interfacing with the external environment.

Acetyltransferases↗

PubMedDate not supplied

Development of UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside in neonatal rats.

Glucuronidation is low or undetectable in embryonic and early fetal tissues and changes to adult levels at rates depending on the acceptor, tissue, and species. Because other data indicate there may be a specific UDP-glucuronosyltransferase (GT) in the liver of adult rats that glucuronidates digitoxigenin-monodigitoxoside (DIG), the development of GT activity in neonatal rats toward DIG was compared with that of other acceptors. Conjugation of p-nitrophenol and 1-naphthol was higher at birth and decreased to adult levels by 20 days of age. Glucuronidation of chloramphenicol, morphine, valproic acid, and bilirubin increased from birth to adult activity by 20 days of age. Conjugation of phenolphthalein, estrone, and diethylstilbestrol was low in 1-day-old rats and higher than adult in 20-day-old animals. In contrast, glucuronidation of DIG was barely detectable (9% of adult) in 20-day-old rats. The concentration of UDP-glucuronic acid was 50% of adult levels at birth and increased to adult values by 10 days of age. Administration of 3-methylcholanthrene on days 6 to 9 after birth significantly stimulated GT activity toward 1-naphthol, p-nitrophenol, and morphine, whereas phenobarbital precociously increased conjugation of chloramphenicol, valproic acid, morphine, and diethylstilbestrol. Pregnenolone-16 alpha-carbonitrile enhanced the development of GT activity toward morphine, chloramphenicol, valproic acid, bilirubin, diethylstilbestrol, and estrone. Glucuronidation of DIG was not increased after 3-methylcholanthrene or phenobarbital, but could be induced after pregnenolone-16 alpha-carbonitrile to 7% of adult values in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Alterations in biliary excretory function by streptozotocin-induced diabetes.

Hepatic clearance and biliary excretion of model substrates for each of four carrier-mediated transport systems were studied in male Sprague-Dawley rats treated 28 days earlier with 45 mg/kg streptozotocin iv to induce uncontrolled insulin-deficient diabetes. Diabetic rats exhibited hyperglycemia (560 mg/dl), polyuria (160 ml/24 hr), polyphagia, polydipsia, and generalized myopathy. The plasma disappearance, biliary excretion, and elimination half-life of the anionic dye phenol red was unchanged in diabetic rats, but total clearance of phenol red was increased. Conjugation of phenol red with glucuronic acid appeared to be increased in diabetic rats, whereas acetylation of procainamide ethobromide was decreased. Plasma elimination and total clearance of cationic procainamide ethobromide, uncharged ouabain, and the bile acid taurocholate were significantly increased in diabetic animals. Biliary excretion of these three compounds was only slightly elevated in the first 15 min after administration and was decreased after 1 hr. Biliary and total systemic clearance were also increased from 2-3-fold for procainamide ethobromide, ouabain, and taurocholate. These changes in clearance are predominantly due to the 2-5-fold increase in steady state volume of distribution. Basal bile flow rates were increased by 62% after the induction of diabetes to 88 microliter/min/kg. Diabetic rats secreted higher levels of bile acids, cholesterol, and phospholipids into bile. These data indicate that long term insulin-dependent diabetes does alter hepatic excretory function.

Animals↗

PubMedDate not supplied

Induction of UDP-glucuronosyltransferase activities in Gunn, heterozygous, and Wistar rat livers by pregnenolone-16 alpha-carbonitrile.

The effect of pregnenolone-16 alpha-carbonitrile (PCN) on UDP-glucuronosyltransferase (UDP-GT) activity was comprehensively examined in Wistar (JJ), heterozygous (Jj) and Gunn (jj) rats with eleven different acceptors for glucuronic acid. UDP-GT activity after 3-methylcholanthrene (3-MC) and phenobarbital (PB) treatment was studied in additional rats for comparative purposes. Conjugation of group-1 aglycones (1-naphthol and p-nitrophenol) was much lower in Gunn than in Wistar rats. PCN did not alter UDP-GT conjugation of these acceptors. UDP-GT activity toward group-1 aglycones was increased by 3-MC in Wistar and heterozygous rats but was not enhanced in Gunn rats by any inducer. Activity toward group-2 aglycones (morphine, chloramphenicol, valproic acid) was similar in control rats of all genotypes. PCN increased chloramphenicol conjugation, whereas PB enhanced the glucuronidation of all group-2 aglycones in Wistar, heterozygous, and Gunn rats. Conjugation of group-3 acceptors (bilirubin and digitoxigenin monodigitoxoside, DIG) was deficient in Gunn rats and was not inducible. PCN increased glucuronidation of bilirubin and DIG in Wistar and heterozygous rats. The concentration of UDP-glucuronic acid (UDPGA) in liver was similar in control animals of all genotypes and was increased in rats treated with 3-MC. The other inducers did not affect hepatic UDPGA levels. Thus, 3-MC, PB, and PCN induce UDP-GT activities toward different groups of acceptors of glucuronic acid. The results support the hypothesis that PCN induces a form of UDP-GT that preferentially conjugates the group-3 acceptors, bilirubin and DIG.

Animals↗

PubMedDate not supplied

Chemically-induced alteration of UDP-glucuronic acid concentration in rat liver.

Since many xenobiotics alter hepatic UDP-glucuronosyltransferase activity, their effect on UDPGA concentration was determined. Rats were pretreated with: 1) microsomal enzyme inducers (7,8-benzoflavone, benzo(a)pyrene, butylated hydroxyanisole, isosafrole, 3-methylcholanthrene, phenobarbital, pregnenolone-16 alpha-carbonitrile (PCN), 2,3,7,8-tetrachlorodibenzo-p-dioxin, trans-stilbene oxide); 2) inhibitors of microsomal enzymes (cobaltous chloride, piperonyl butoxide, SKF 525-A, borneol, galactosamine); 3) hepatotoxins (allyl alcohol, aflatoxin B1, alpha-naphthylisothiocyanate, bromobenzene, cadmium chloride, carbon tetrachloride, 1,1-dichloroethylene), and 4) commonly used anesthetics (pentobarbital, urethane, diethyl ether, halothane, enflurane, methoxyflurane). Rats were decapitated before removal of the liver. All inducers except PCN and isosafrole increased UDPGA 36-85% above control. Mixed-function oxidase inhibitors had no effect whereas borneol and galactosamine reduced UDPGA 85-90%. Aflatoxin B1 and cadmium produced decreases of 59 and 25%, respectively. Hepatic UDPGA content was diminished 70-95% after exposure to the inhalation anesthetics, whereas the other anesthetics reduced UDPGA about 25%. Thus, numerous xenobiotics alter the concentration of UDPGA in rat liver, which may influence the rate of glucoronidation.

Anesthetics↗

PubMedDate not supplied

Chronic voluntary exercise may alter hepatobiliary clearance of endogenous and exogenous chemicals in rats.

A chronic voluntary exercise paradigm, which mimics the exercise pattern of many humans, influences the hepatic clearance of several organic anions and a bile acid, whereas a neutral organic compound is seemingly unaffected. To extend these observations, the present work has evaluated in female Sprague-Dawley rats the effect of 6 weeks of voluntary running on the hepatobiliary elimination of endogenous bile acids and glutathione and exogenously injected rose bengal, digoxin, and acetaminophen. Inactive rats had mobility limited to their cages, whereas exercised rats had free access to a 44-in running wheel. In comparison to weight-matched sedentary rats, the exercised rats ran 4.3 +/- 0.3 miles/day, consumed 45% more food daily, had slightly greater liver/body weight ratios, and slightly elevated basal bile flow rates. Biliary excretion of endogenous bile acids was increased significantly, and excretion of reduced and oxidized glutathione was increased in exercised rats by 190% and 173% of sedentary levels, respectively. Total clearance, biliary clearance, and maximal biliary excretion of the injected organic anion rose bengal (60 mumol/kg) were elevated in exercised rats by 86%, 440%, and 85%, respectively. In contrast, there were no observed differences in pharmacokinetic parameters, serum elimination, or biliary excretion for the clinically important cardiac glycoside digoxin (dose of 100 nmol/kg). Finally, study of the analgesic acetaminophen (330 mumol/kg) revealed that total and biliary clearances were increased by 37% and 42%, respectively, in exercised rats, whereas steady-state volume of distribution and elimination half-life were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗