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Biomedical subjects

J B Watkins

Publications and source records attributed to J B Watkins.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of volatile anesthetics on the hepatic UDP-glucuronic acid pathway in mice.

Large, rapid decreases in hepatic UDP-glucuronic acid concentrations occur in rats following exposure to myriad chemicals. In fact, 80% reductions in UDP-glucuronic acid occur within minutes after exposure to inhalation anesthetics. The present study was designed to determine whether this decrease in hepatic UDP-glucuronic acid may be due to (a) a decrease in the precursor UDP-glucose; (b) decreased activity of UDP-glucose dehydrogenase, which oxidizes UDP-glucose to UDP-glucuronic acid; (c) increased activity of UDP-glucuronosyltransferases; or (d) increased activity of nucleotide pryophosphatase, which degrades UDP-glucuronic acid to glucuronic acid-1-phosphate. Exposure to halothane, isoflurane and sevoflurane decreased UDP-glucuronic acid concentrations by 40-52% as compared to that in unanesthetized control mice. No sex-dependent or anesthetic-induced effects of UDP-glucose levels and the activities of UDP-glucose dehydrogenase and UDP-glucuronosyltransferase were observed. Nucleotide pyrophosphatase activity was increased by 47-65% in female mice after inhalation of halothane, isoflurane and sevoflurane. The apparent Vmax for hydrolysis of 4-nitrophenol thymidine 5'-monophosphate ester by nucleotide pyrophosphatase was increased by 56-80% in female mice, whereas the apparent Km was unchanged. These alterations in nucleotide pyrophosphate kinetics may be responsible, in part, for the marked decrease of hepatic UDP-glucuronic acid concentrations by the volatile anesthetics.

Anesthetics↗
PubMed1990

Role of nucleotide pyrophosphatase in enflurane-induced reduction of UDP-glucuronic acid concentration in mouse liver.

Because hepatic UDP-glucuronic acid levels decrease upon exposure to volatile anesthetics, the present study was designed to determine the mechanism by which enflurane decreases UDP-glucuronic acid in mice by measuring the concentrations of intermediates and the activities of enzymes in the UDP-glucuronic acid pathway. UDP-glucuronic acid concentrations were decreased by 40% in both male and female mice after 10 min of enflurane-induced narcosis. Concentration of UDP-glucose and the activities of diethylstilbestrol UDP-glucuronosyltransferase and UDP-glucose dehydrogenase were not affected by enflurane treatment. In contrast, nucleotide pyrophophatase activity was increased approximately 50% in both sexes. Thus, the decrease in hepatic UDP-glucuronic acid upon exposure of mice to enflurane is probably due to increased degradation by nucleotide pyrophosphatase.

Animals↗
PubMed1990

Taurocholate transport by brush-border membrane vesicles from the developing rabbit ileum: structure/function relationships.

To examine the ontogenesis of bile acid transport in the rabbit ileum, brush-border membrane vesicles (12- to 20-fold purified) were prepared from 14- to 49-day-old animals. Taurocholate uptake was characterized by the emergence of secondary active, Na(+)-dependent transport at the start of weaning (21 days). Transient intravesicular accumulation (overshoot) of taurocholate occurred at 5-10 s of incubation, and the overshoot maximum increased significantly from 21 days (349.2 +/- 22.4 nmol/mg protein) to 35 days (569.0 +/- 84.3 nmol/mg protein; p less than 0.001), without further increase at maturity (49 days, not equal to 607.6 +/- 136.7 nmol/mg protein). No significant taurocholate active uptake component was noted at 14 days; however, ileal vesicles from sucklings showed carrier-mediated, Na+ D-glucose cotransport. In greater than or equal to 35-day-old rabbits, osmolarity studies at 20 s of incubation showed that only approximately 12% of [14C]taurocholate uptake was secondary to bile acid-to-membrane binding. Conversely, at 20 min, greater than 95% of radiolabel incorporation represented solute bound to the external and/or internal membrane surface. Arrhenius plots establish brush-border membrane taurocholate uptake as an intrinsic, lipid-dependent process, with a slope discontinuity between 24 and 28 degrees C, similar to the membrane lipid thermotropic transition region. Steady-state fluorescence polarization studies (1,6-diphenyl-1,3,5-hexatriene) demonstrate a temporal association between the maturation of taurocholate uptake and age-related decreases in ileal brush-border membrane fluidity. These data indicate that maturation of bile acid secondary active transport in the rabbit ileum may be regulated, at least in part, by changes in brush-border membrane lipid dynamics.

Age Factors↗
PubMed1990

Procedural compliance and clinical outcome associated with therapeutic interchange of extended-spectrum penicillins.

The degree of procedural compliance and the clinical outcome associated with a therapeutic interchange of extended-spectrum penicillins were assessed. Pharmacists conducted a concurrent chart review on all patients receiving mezlocillin as a therapeutic alternative for piperacillin or ticarcillin over a five-month period. The pharmacists assessed whether (1) the pharmacy appropriately dispensed mezlocillin when orders were written for piperacillin or ticarcillin, (2) physicians and nurses were properly notified of the therapeutic interchange, and (3) the bacterial isolates were susceptible to mezlocillin. Pharmacists and physicians evaluated clinical outcomes of all patients receiving mezlocillin through a retrospective chart review and classified the responses as "success," "failure," or "indeterminate." Fifty-one orders for piperacillin were written during the study period, and mezlocillin was selected as a therapeutic alternative in all cases. No orders for ticarcillin were written. Proper notification was made to nurses and physicians in 98% and 65% of cases, respectively. No mezlocillin-resistant gram-negative bacteria were found. Eighty-three courses of therapy were reviewed for clinical outcome; 68 were classified as successes, 0 were failures, and 15 were indeterminate. The cost savings after nine months of therapeutic interchange of mezlocillin for piperacillin was $6600. This study indicates that the pharmacy made a proper therapeutic interchange of mezlocillin for piperacillin and followed the correct procedure for notification of the nursing staff. However, more effort is needed to ensure communication with the prescribing physicians.

Bacteria↗
PubMed1989

Skeletal muscle in the diabetic mouse: histochemical and morphometric analysis.

Despite the extensive literature concerning the neuropathy associated with diabetes, only limited information describes changes in the associated muscle. The objective of this study was to evaluate the histochemical and morphometric characteristics of diabetic muscle in the C57BL/KsJ db-m strain of mouse. The histochemical analysis of myofiber type for the diabetic mouse revealed that the extensor digitorum longus muscle consisted of 53.1% type 2a, 46.0% type 2b, and 0.9% type 1 myofibers, a significant shift from the percentages found in the nondiabetic litter mates (44.4% type 2a, 55.6% type 2b, no type 1). Computer-assisted morphometric analysis of myofiber size by fiber type indicated a significant difference in myofiber size for the type 2b fibers in muscles from diabetic mice. Similarly, there was a shift in the fiber size distribution to include a greater number of small type 2b myofibers when compared to controls. Skeletal muscle from diabetic mice exhibited a significant change in the percentage of fiber types, with an increase in the number of type 2a fibers, a fiber type grouping that implies possible denervation and reinnervation, and a decrease in myofiber size. These findings may explain why some diabetic patients complain of muscle weakness.

Animals↗
PubMed1989

Carbon tetrachloride and the sorbitol pathway in the diabetic mouse.

1. Sorbitol dehydrogenase activity and the hepatic and serum concentrations of sorbitol, glucose and fructose were quantified in diabetic mice. 2. Blood glucose concentrations were increased over 300% by diabetes and were decreased toward normal after insulin-treatment. 3. Hepatic sorbitol concentrations ranged from 7-15 mumol/g and were highest in uncontrolled diabetic mice. 4. Hepatic concentrations of fructose and sorbitol were not affected by insulin administration. 5. Challenge with carbon tetrachloride (25 microliters/kg i.p.) did not alter concentrations of glucose, sorbitol or fructose in blood or liver. 6. Sorbitol dehydrogenase activity in blood was increased similarly in normal, diabetic and insulin-treated diabetic mice after CCl4 administration. 7. The data indicate that sorbitol did not accumulate in diabetic mice, and that induction of diabetes did not increase the susceptibility of mice to CCl4 hepatotoxicity as occurs in rats.

Animals↗
PubMed1989

Comparison of glucose, sorbitol and fructose accumulation in lens and liver of diabetic and insulin-treated rats and mice.

1. The accumulation of glucose, fructose and sorbitol was determined in the lens, liver, and blood from normal, streptozotocin-induced diabetic, and insulin-treated diabetic rats and mice. 2. Sorbitol concentration in rat lens was 10-100 times greater than that in mouse lens, with the highest concentrations in the diabetic animals. 3. Sorbitol levels in rat and mouse liver, and mouse lens were similar and increased only slightly under hyperglycemic conditions. 4. Fructose accumulation was similar in rat and mouse liver and was elevated in the diabetic mouse blood and diabetic rat lens. 5. Aldose reductase activity in rat lens was approximately 350 times that of mouse lens. 6. Lenticular sorbitol dehydrogenase activity in rats was approximately ten times that in mouse lens. 7. Administration of insulin tended to lower liver glucose and subsequent sorbitol formation in the diabetic rat and mouse.

Aldehyde Reductase↗
PubMed1989

The "psychosomatic family" model: an empirical and theoretical analysis.

Evolution of the Family Systems Paradigm has been constrained by the dichotomy between theory building and empirical research. This article integrates these two domains by presenting a theoretical analysis of the "psychosomatic family" model as it informs and is informed by an empirical research project. Forty families of children with Crohn's disease (CD), ulcerative colitis (UC), and functional recurrent abdominal pain syndrome (RAP) were rated during standard, videotaped family interaction tasks, lunch, and interview. Laboratory scores of disease activity were associated with triangulation, marital dysfunction, and total "psychosomatic family" scores. Disease activity was not significantly correlated with enmeshment, overprotection, rigidity, conflict avoidance, or poor conflict resolution. Thus, the marital/triangulation and enmeshment/overprotection/conflict clusters may be subcomplexes of the "psychosomatic family" complex. CD, UC, and RAP groups differed in the relations among particular family patterns and disease activity. A heuristic family-psycho-somatic model is presented to facilitate future research.

Abdominal Pain↗
PubMed1989

Exposure of rats to inhalational anesthetics alters the hepatobiliary clearance of cholephilic xenobiotics.

Several recent studies indicate that anesthesia-induced alteration of UDP-glucuronic acid concentrations can affect the rate of xenobiotic glucuronidation by UDP-glucuronosyltransferases. Other data demonstrate that the biliary excretion of several cholephilic drugs is depressed in rats anesthetized with diethyl ether. The present study has examined the effect of 2% halothane, 1.5% isoflurane, 2% enflurane and 3% sevoflurane on the clearance and biliary excretion of acetaminophen, digoxin, phenol red and phenol-3,6-dibromphthalein disulfonate. All volatile anesthetics reduced hepatic UDP-glucuronic acid concentrations 50 to 75%. Biliary excretion of acetaminophen as well as the glucuronide and sulfate conjugates was depressed by all anesthetics for about 1 hr, whereas biliary excretion of the glutathione conjugate was increased during this time. Although total clearance, elimination half-life and steady-state volume of distribution were not altered, biliary clearance of acetaminophen was decreased by 39 to 50%. Formation of the glucuronide conjugate of phenol red and its biliary excretion were depressed by all volatile anesthetics; however, total clearance was increased by 15 to 25% during isoflurane or sevoflurane anesthesia. Total clearance and steady-state volume of distribution of digoxin were decreased only in rats exposed to halothane. There were no changes in biliary excretion. Urinary clearance of digoxin was increased by all volatile anesthetics, whereas biliary clearance was decreased by halothane and enflurane. Biliary excretion, clearance and volume of distribution of phenol-3,6-dibromphthalein disulfonate were not altered by the anesthetics. These data indicate that the hepatobiliary elimination of the glucuronidated metabolites is reduced in rats exposed to volatile anesthetics.

Acetaminophen↗
PubMed1988

Bile salt binding properties of commonly used gastrointestinal drugs: maalox, carafate, and questran.

We have validated a method to measure bile salt binding by Maalox (aluminum hydroxide and magnesium hydroxide), Carafate (sucralfate), and Questran (cholestyramine) in vitro. The method used in this study involves a correction for adherent water volume and thus provides a correct measure of bile salt binding. With this approach, we described the binding properties of Maalox, Carafate, and Questran. The bile salt binding capacities of Carafate and Maalox are limited and do not have physiological or pharmacological significance. On the other hand, we found that Questran has substantial bile salt binding capacity. At the recommended dosage, Questran could deplete the total bile salt pool. We also found that Carafate, although not used as an antacid, has buffering capacity (maintaining a pH of solution in the range 4.2-4.8) which might contribute to its effectiveness as an ulcer treatment drug.

Aluminum Hydroxide↗
PubMed1988

The effect of long-term streptozotocin-induced diabetes on the hepatotoxicity of bromobenzene and carbon tetrachloride and hepatic biotransformation in rats.

To exclude the possibility that changes in hepatotoxicity and biotransformation were induced by diabetogen administration, the influence of long-lasting experimental insulin-dependent diabetes on the activities of benzphetamine demethylase, styrene oxide hydrolase, and UDP-glucuronosyl-transferases toward 1-naphthol, diethylstilbestrol, estrone and testosterone, and glutathione S-transferases toward 1-chloro-2,4-dinitrobenzene, ethacrynic acid, and sulfobromophthalein was studied. Adult male Sprague-Dawley rats injected with 45 mg streptozotocin/kg rapidly developed the classical symptoms of diabetes which persisted throughout the 90-day test period. Ketonemia was detectable at 6 but not at either 35 or 90 days after streptozotocin administration. After acute challenge with bromobenzene or carbon tetrachloride (CCl4), aspartate and alanine aminotransferase activities in rats diabetic for 35 and 90 days were markedly higher than those in normal rats, suggesting that diabetes potentiated the hepatotoxicity of these chemicals. Administration of 25 microliters CCl4/kg, ip, to diabetic rats decreased enzyme activities toward benzphetamine, sulfobromophthalein, 1-chloro-2,4-dinitrobenzene, and 1-naphthol. In normal rats, a dose of 400 microliters CCl4/kg, ip, was required to cause similar changes in enzyme activities. Bromobenzene (500 microliters/kg, ip) elicited opposing responses in diabetic and normal rats in N-demethylase activity, in UDP-glucuronosyltransferase activity toward 1-naphthol, estrone, and testosterone, and in glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene. Total cytochrome P450 concentrations were reduced by both induction of diabetes and hepatotoxicant challenge. Thus, chronic uncontrolled diabetes alters the response of hepatic xenobiotic biotransformation enzymes in a non-uniform, substrate-dependent manner, independent of initial diabetogen effects. The role of cytochrome P450j in potentiating CCl4 toxicity is discussed.

Animals↗
PubMed1988

Hepatic phase II biotransformation in C57Bl/KsJ db/db mice: comparison to that in Swiss Webster and 129 REJ mice.

1. Cytochrome P-450 concentrations were similar in male and female carrier (db/+) and diabetic (db/db) mice. Benzphetamine N-demethylase and styrene oxide hydrolase activities were 47 and 65% lower in db/+ than in db/db mice. 2. UDP-Glucuronosyltransferase activity toward 1-naphthol, estrone and diethylstilbestrol was not different between db/db and db/+, but was 40% higher in db/db mice toward testosterone. 3. Glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene and ethacrynic acid was 47 and 59% lower in db/db mice than in male db/+ mice. Female db/+ mice had similar activities to those found in diabetic animals. 4. The differences in enzyme activity between hyperinsulinemic and normal animals suggest that insulin can influence both phase I and phase II biotransformations. 5. Enzyme activities in db/+ and db/db mice were compared to those in 129 REJ and Swiss Webster mice.

Animals↗
PubMed1988

Sibling psychological status and style as related to the disease of their chronically ill brothers and sisters: implications for models of biopsychosocial interaction.

This study explores the relationship between disease type and disease activity, and the psychological status of siblings of chronically ill children. Closest-age siblings of children with Crohn's disease (CD) (n = 41) and ulcerative colitis (UC) (n = 24) were assessed for psychological disorder and psychological style, using reliable and standardized measures. The disease activity of the patients was also evaluated. Assessment occurred during outpatient visits to a pediatric gastroenterology division. Results indicated that CD siblings had more psychological disorder than UC siblings. This was not due to greater acute disease activity in the CD patients. However, as a group, siblings of the sickest CD patients displayed more "internalizing" behaviors, whereas siblings of the healthiest CD patients displayed more "externalizing" behaviors. UC siblings, who were psychologically healthier, displayed "externalizing" behaviors regardless of the patient's disease activity. These results are in accord with our previous findings on family functioning, which, together, yield a heuristic model representing the different patterns of biopsychosocial interaction for CD in contrast to UC.

Adolescent↗
PubMed1987

Hepatic biotransformation in lean and obese Wistar Kyoto rats: comparison to that in streptozotocin-pretreated Sprague-Dawley rats.

1. Phase I and phase II biotransformation was compared in streptozotocin-induced hypoinsulinemic (STZ) and genetic hyperinsulinemic (WKY-fatty) rats. 2. Total cytochrome P-450 concentrations were reduced in both STZ and WKY, whereas styrene oxide hydrolase and benzphetamine N-demethylase activities were normal in STZ and reduced in WKY. 3. UDP-glucuronosyltransferase activity was decreased toward testosterone and 1-naphthol in STZ and WKY, and was increased toward estrone in the obese female WKY. 4. Glutathione S-transferase activity was decreased in STZ toward 1-chloro-2,4-dinitrobenzene, ethacrynic acid and sulfobromophthalein, but was similar to that in normal rats for WKY.

Animals↗
PubMed1987

Pneumatic dilatation and operative treatment of achalasia in children.

The therapeutic approach to children with achalasia of the esophagus is controversial. Both pneumatic dilatation (PD) and Heller esophageal myotomy (EM) are considered effective, while bougienage has been discarded by most authorities. To determine the best place for each in the therapy of achalasia, 19 cases treated since 1964 were reviewed. Ages ranged from 9 months to 17 years (median 11 years), and duration of symptoms ranged from 4 months to 8 years (median 1 year). Three patients had symptoms from infancy. Two patients underwent a successful EM as their sole procedure. Two underwent bougienage as their initial therapy. Dysphagia recurred quickly and both required operation. Fifteen underwent PD under intravenous sedation with a Brown-McHardy dilator placed under fluoroscopy. Seven underwent a single dilatation; seven underwent two; and one underwent four. Relief of dysphagia was achieved in 11 patients, but four required surgery. The patients who experienced adequate relief with dilatation alone were clinically identical to those in whom it failed with respect to age, race, sex, symptom duration, and manometric data. Those who required EM following PD experienced only a brief period of relief following PD (median 1 month) compared with those who enjoyed lasting results (median 18 months). Three patients suffered prolonged chest pain or fever following PD, but without esophageal leakage and with full recovery. Two of eight operative patients developed late postoperative reflux. There were no deaths. Both PD and EM are safe and effective treatments for achalasia. Our results indicate that dilatation is the logical first therapeutic step, but rapid recurrence of symptoms may identify those patients who will require operative myotomy.

Adolescent↗
PubMed1987

Characterization of xenobiotic biotransformation in hepatic, renal and gut tissues of cattle and sheep.

Microsomal and cytosolic preparations of hepatic, renal, ileal and ruminal tissues of cattle and sheep were used to measure oxidative, hydrolative and conjugative biotransformations of 11 xenobiotic substrates. Within species, enzyme activities were generally higher (P less than .05) in hepatic than non-hepatic tissue but, in both species, non-hepatic tissue exhibited considerable capacities for metabolizing certain substrates. Sheep rumen wall (with papillae) was notably high in cytochrome P-450 content (34% of hepatic value), in glutathione conjugation of ethacrynic acid (223% of hepatic activity; P less than .05), and UDP-glucuronidation of estrone (290% of hepatic activity; P less than .05). Sheep differed (P less than .05) from cattle, having lower cytochrome P-450 content in liver and ileum (but not kidney); lower N-demethylase activity in liver, but two- to threefold higher activity in kidney; lower sulfotransferase activity in liver and kidney; and higher glutathione S-transferase activity toward certain substrates. UDP-glucuronidation varied too widely among substrates to afford strong generalization in comparisons among tissues or between species. Non-hepatic tissues in ruminants exhibit considerable capacities for oxidative, hydrolative and conjugative metabolism of xenobiotics. Sheep and cattle differ widely in hepatic and non-hepatic capacities for biotransforming certain xenobiotics.

Animals↗
PubMed1986

Effects of ethinyl estradiol on intestinal membrane structure and function in the rabbit.

Structural and functional properties of the small intestinal microvillus membrane were evaluated in the rabbit after administration of ethinyl estradiol, a synthetic estrogen with a demonstrated propensity to alter hepatic membrane lipid fluidity, and promote cholestasis. In the jejunum, no estrogen-induced changes in microvillus membrane total lipid, cholesterol or phospholipid content were observed. However, the ileal microvillus membrane in estradiol-treated animals demonstrates significant reductions vs. controls (per mg protein) in total lipid (0.55 milligrams vs. 0.89 milligrams) [corrected] and phospholipid (206.7 micrograms vs. 304.91 micrograms) (p less than 0.001) content, as well as modifications in specific phospholipid species. The increase in the ileal microvillus membrane cholesterol: phospholipid molar ratio (0.65 vs. 0.51, p less than 0.05) was associated with a significant decrease in membrane lipid fluidity reflected by an increase in fluorescence anisotropy measurements utilizing diphenyl hexatriene as the fluorophore (r at 25 degrees C = 0.306 vs. 0.282, p less than 0.05). Thermotropic lipid phase transitions, assessed by Arrhenius plots of both fluorescence data and ileal microvillus membrane p-nitrophenylphosphatase activity demonstrate that phase changes occur between and 24 and 28 degrees C in both treated and untreated groups. Within the temperature range studied (40-10 degrees C) no differences from control were observed in microvillus membrane alkaline phosphatase activity following estrogen treatment. These data therefore indicate that ethinyl estradiol-induced effects on microvillus membrane lipid composition and physical properties occur predominantly in the ileum and appear to be related, in part, to specific alterations in the availability of phospholipid following estrogen treatment.

4-Nitrophenylphosphatase↗