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PubMed2005

Degradation of beta-Hexachlorocyclohexane by Haloalkane Dehalogenase LinB from Sphingomonas paucimobilis UT26.

Beta-Hexachlorocyclohexane (beta-HCH) is the most recalcitrant among the alpha-, beta-, gamma-, and delta-isomers of HCH and causes serious environmental pollution problems. We demonstrate here that the haloalkane dehalogenase LinB, reported earlier to mediate the second step in the degradation of gamma-HCH in Sphingomonas paucimobilis UT26, metabolizes beta-HCH to produce 2,3,4,5,6-pentachlorocyclohexanol.

Bacterial Proteins↗
PubMed1977

Purification and properties of cis-toluene dihydrodiol dehydrogenase from Pseudomonas putida.

The purification of (+)-cis-1(S),2(R)-dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase from cells of Pseudomonas putida grown with toluene as the sole source of carbon and energy is reported. The molecular weight of the enzyme is 104,000 at pH 9.7. The enzyme is composed of four apparently identical subunits with molecular weights of 27,000. The enzyme is specific for nicotinamide adenine dinucleotide and oxidizes a number of cis-dihydrodiols. Both enantiomers of a racemic mixture of cis-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol are oxidized by the enzyme. No enzymatic activity is observed with trans-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol.

Amino Acids↗
PubMed1994

Cloning and sequencing of a 2,5-dichloro-2,5-cyclohexadiene-1,4-diol dehydrogenase gene involved in the degradation of gamma-hexachlorocyclohexane in Pseudomonas paucimobilis.

In Pseudomonas paucimobilis UT26, gamma-hexachlorocyclohexane (gamma-HCH) is converted to 2,5-dichloro-2,5-cyclohexadiene-1,4-diol (2,5-DDOL), which is then metabolized to 2,5-dichlorohydroquinone. Here, we isolated from the genomic library of UT26 two genes which expressed 2,5-DDOL dehydrogenase activity when they were transformed into P. putida and Escherichia coli. Both gene products had an apparent molecular size of 28 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The first gene, named linC, located separately from the two genes (linA and linB) which we had already cloned as genes involved in the gamma-HCH degradation. The other, named linX, located about 1 kb upstream of the linA gene encoding gamma-HCH dehydrochlorinase. A gamma-HCH degradation-negative mutant, named UT72, which lacked the whole linC gene but had the intact linX gene was isolated. The linC gene given in a plasmid could complement UT72. These results strongly suggest that the linC gene but not the linX gene is essential for the assimilation of gamma-HCH in UT26. Deduced amino acid sequences of LinC and LinX show homology to those of members of the short-chain alcohol dehydrogenase family.

Alcohol Oxidoreductases↗
PubMed1979

Improved metabolic profiles in insulin-treated diabetic patients given an alpha-glucosidehydrolase inhibitor.

An alpha-glucosidehydrolase inhibitor (acarbose; BAY g 5421) taken with food was compared with dummy tablets in seven insulin-treated diabetic patients over eight-hour periods that included breakfast, lunch, and two snacks. Acarbose diminished the postprandial increases in blood glucose, lactate, and pyruvate concentrations and may therefore be of value in the management of insulin-dependent diabetes.

Administration, Oral↗
PubMed2003

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

OBJECTIVE: To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. DESIGN: Double blind randomised placebo controlled parallel group study. SETTING: Hospital in Hampshire. PARTICIPANTS: 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. INTERVENTIONS: Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. MAIN OUTCOME MEASURES: Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. RESULTS: The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. CONCLUSIONS: Enzyme potentiated desensitisation showed no treatment effect in this study.

Adult↗
PubMed2006

Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study.

OBJECTIVE: To compare the risk of suicide in adults using the antidepressant venlafaxine compared with citalopram, fluoxetine, and dothiepin. DESIGN: Retrospective cohort study. SETTING: UK General Practice Research Database. PARTICIPANTS: 219,088 patients, aged 18-89 years, who were prescribed venlafaxine, citalopram, fluoxetine, or dothiepin from 1995 to 2005. MAIN OUTCOME MEASURES: Completed suicide and attempted suicide. RESULTS: Venlafaxine users had a higher burden of risk factors for suicide, including previous suicide attempts and proxies for severe depression or depression that was difficult to treat. In the analysis for completed suicides, unadjusted and adjusted hazard ratios for venlafaxine compared with citalopram were 2.44 (95% confidence interval 1.12 to 5.31) and 1.70 (0.76 to 3.80), for venlafaxine compared with fluoxetine were 2.85 (1.37 to 5.94) and 1.63 (0.74 to 3.59), and for venlafaxine compared with dothiepin were 2.54 (1.07 to 6.02) and 1.31 (0.53 to 3.25). Compared with other study drugs, venlafaxine was also associated with an increased risk of attempted suicide, but adjustment for measured confounders substantially reduced the hazard ratios. CONCLUSIONS: Venlafaxine use was consistently associated with higher risk of suicide compared with citalopram, fluoxetine, and dothiepin. Venlafaxine users had a higher burden of suicide risk factors, however, and adjustment for measured confounders substantially reduced the excess risks. Since the secondary data used in this analysis allowed only indirect and partial measurements of potential confounders, it is possible that residual confounding explains much, if not all, of the observed excess risk.

Adolescent↗
PubMed1974

Sites of competition in the selective hepatic uptake of rifamycin-SV, flavaspidic acid, bilirubin, and bromsulphthalein.

In rats both rifamycin-SV and flavaspidic acid impaired the disappearance of bromsulphthalein (BSP) from plasma. The addition of rifamycin-SV to rat liver supernatant containing BSP did not displace BSP from ligandin or Z protein unless it was added in very high concentration. In similar studies in vitro with flavaspidic acid, BSP was displaced from Z protein even at low concentrations of flavaspidic acid, whereas there was only a minor effect on the binding to ligandin. The intravenous administration of rifamycin to Gunn rats raised the plasma bilirubin concentration slightly after 30 minutes whereas flavaspidic acid was without significant effect. At 30 minutes the amount of bilirubin in the liver was markedly reduced by rifamycin and moderately depressed by flavaspidic acid. Although both the rifamycin and flavaspidic acid lowered the bilirubin in cell sap, the main effect of flavaspidic acid appeared to be on binding to Z protein. Rifamycin reduced the amount bound to both ligandin and Z protein. It is suggested that flavaspidic acid acted on the hepatic uptake of bilirubin and BSP predominantly by competing for binding to Z protein. Rifamycin-SV acted at a different site, probably blocking uptake at the plasma membrane.

Animals↗
PubMed1979

Effect of alpha-glucosidehydrolase inhibition and intestinal absorption of sucrose, water, and sodium in man.

The effect of a new complex oligosaccharide exhibiting potent inhibitory action on alpha-glucoside hydrolases on intestinal absorption of sucrose in man was tested by constant in vivo perfusion of the jejunum. At concentrations of 4.65 or 15.5 X 10(-6)M the alpha-glucosidehydrolase inhibitor (alpha-GHI) markedly inhibited absorption of glucose from sucrose and absorption of sodium and water. Oral administration of the alpha-GHI resulted as well in depression of solute, sodium, and water absorption. This new compound can serve as an interesting tool to induce carbohydrate malabsorption by inhibition of final digestion and may possibly be of beneficial therapeutic effect in dietary control of diabetes or obesity.

Adult↗
PubMed1986

Effect of modern analgesic drugs (tramadol, pentazocine, and buprenorphine) on the bile duct sphincter in man.

Modern narcotic analgesic drugs, such as tramadol, pentazocine, and buprenorphine share similarities of molecular structure with morphine which is widely believed to cause spasm of the bile duct sphincter and so impede bile flow. This study assessed the effects of intravenously administered analgesics on bile duct sphincter motor activity measured by ERCP manometry. Ten minutes after pentazocine injection the duration of contractions and baseline pressure of the bile duct sphincter rose from 6.2 +/- 0.2 to 8.2 +/- 0.27 s and from 5.1 +/- 0.6 to 8.8 +/- 0.4 mmHg respectively. Tramadol, buprenorphine and saline showed no such effect. These data indicated that the effects of such drugs on bile duct sphincter function can be safely assessed by ERCP manometry and that pentazocine adversely affects the bile duct sphincter, whilst tramadol and buprenorphine do not. We consider therefore that pentazocine is not the premedication of first choice for endoscopic procedures involving the sphincter of Oddi and should also be avoided in patients with pancreatic and biliary disorders.

Adult↗
PubMed2000

Venlafaxine-induced serotonin syndrome with relapse following amitriptyline.

A case of venlafaxine-induced serotonin syndrome is described with relapse following the introduction of amitriptyline, despite a 2-week period between the discontinuation of one drug and the commencement of the other. Electroencephalography may play an important part in diagnosis. With the increasing use of selective serotonin re-uptake inhibitors, greater awareness of the serotonin syndrome is necessary. Furthermore, the potential for drug interactions which may lead to the syndrome needs to be recognised.

Adrenergic Uptake Inhibitors↗
PubMed1988

The mucolytic effect of Sputolosin in horses with respiratory disease.

The effect of the mucolytic drug Sputolosin on the clinical signs of respiratory disease among 28 matched pairs of horses was examined. Compared with the untreated group, the treated group showed a significant decrease in the frequency of coughing and a decreased time to resolution of both cough and nasal discharge. The results indicate that the drug is potentially useful in the management of respiratory disease characterised by an abnormal or increased production of mucus.

Animals↗
PubMed1979

Patulin biosynthesis: the metabolism of phyllostine and isoepoxydon by cell-free preparations from Pencillium urticae.

Cell-free extracts of Penicillium urticae (NRRL 2159A), and its Pat- mutants, J2, J1, and S11, were found to contain significant NADP-dependent isoepoxydon dehydrogenase activity. This reversible interconversion of the epoxides (-)-phyllostine and (+)-isoepoxydon occurred optimally at pH 5.8 and was completely inhibited by 1 mM p-chloromercuribenzoate (PCMB). The cytosol enzyme possessed specificity for both substrate and cofactor since neither (+)-epoxydon, an epimer of (+)-isoepoxydon, nor NADH was utilized. Cell extracts of the parent and of mutant J2, which is blocked before the epoxides in the patulin pathway, were found to convert phyllostine and isoepoxydon to a number of unknown metabolites which appeared as yellow spots on thin-layer chromatograms after spraying with a chromogenic reagent. Extracts of mutant J1 were unable to carry out this conversion, while whole cells of mutant S11 accumulated what appeared to be these same 'yellow' compounds. Since PCMB-treated extracts of J2 converted phyllostine but not isoepoxydon to these new metabolites, phyllostine appeared to be their more immediate precursor. The relative positions of isoepoxydon and phyllostine in the patulin pathway are discussed.

Cell-Free System↗
PubMed2002

Cardiovascular effects of 1,8-cineole, a terpenoid oxide present in many plant essential oils, in normotensive rats.

The cardiovascular effects of i.v. treatment with 1,8-cineole, a monoterpenic oxide present in many plant essential oils, were investigated in normotensive rats. This study examined (i) whether the autonomic nervous system is involved in the mediation of 1,8-cineole-induced changes in mean aortic pressure (MAP) and heart rate (HR) and (ii) whether the hypotensive effects of 1,8-cineole could result from its vasodilatory effects directly upon vascular smooth muscle. In both pentobarbital-anesthetized and conscious, freely moving rats, bolus injections of 1,8-cineole (0.3-10 mg/kg, i.v.) elicited similar and dose-dependent decreases in MAP. Concomitantly, 1,8-cineole significantly decreased HR only at the highest dose (10 mg/kg). Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardic responses to 1,8-cineole (10 mg/kg) without affecting hypotension. In conscious rats, i.v. pretreatment with methylatropine (1 mg/kg), atenolol (1.5 mg/kg), or hexamethonium (30 mg/kg) had no significant effects on the 1,8-cineole-induced hypotension, while bradycardic responses to 1,8-cineole (10 mg/kg) were significantly reduced by methylatropine. In rat isolated thoracic aorta preparations, 1,8-cineole (0.006-2.6 mM) induced a concentration-dependent reduction of the contraction induced by potassium (60 mM). This is the first physiological evidence that i.v. treatment with 1,8-cineole in either anesthetized or conscious rats elicits hypotension; this effect seems related to an active vascular relaxation rather than withdrawal of sympathetic tone.

Animals↗