Treatment of arterial hypertension with tienilic acid, a new diuretic with uricosuric properties.
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Tienilic acid--2,3-dichloro-4-(2-thienyl-carbonyl)phenoxyacetic acid--is a new diuretic with uricosuric properties. Nineteen patients with moderate arterial hypertension were treated for 5 consecutive weeks in a randomized fashion in a double-blind study with either tienilic acid or hydrochlorothiazide. Blood pressure was significantly reduced and to the same degree with both drugs. In 7 of the 11 patients receiving tienilic acid the daily dose was increased from 250 to 500 mg after 2 weeks, and in 2 of the 8 patients taking hydrochlorothiazide the daily dose was increased from 50 to 100 mg. Because of the potent uricosuric action of tienilic acid the mean serum urate concentration decreased from 6.3 to 3.3 mg/dL in the patients taking the drug. In contrast, the patients receiving hydrochlorothiazide the mean serum urate concentration increased from 6.1 to 7.8 mg/dL. Moderate hypokalemia of almost identical degree (mean serum potassium values 3.6 and 3.5 mmol/L) and mild metabolic alkalosis were observed in both groups. Tienilic acid had a marked hypocalciuric effect, which was of the same magnitude as the observed with hydrochlorothiazide. During the 5 weeks of treatment no significant change in renal or liver function was observed in either group. There were no hematologic complications and the drug was remarkably well tolerated. Tienilic acid, because of its unique character as a diuretic, hypouricemic and antihypertensive agent, should become the preferred drug for the treatment of arterial hypertension. (+info)
Phenoxyacetic acid degradation by the 2,4-dichlorophenoxyacetic acid (TFD) pathway of plasmid pJP4: mapping and characterization of the TFD regulatory gene, tfdR.
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Plasmid pJP4 enables Alcaligenes eutrophus JMP134 to degrade 3-chlorobenzoate and 2,4-dichlorophenoxyacetic acid (TFD). Plasmid pRO101 is a derivative of pJP4 obtained by insertion of Tn1721 into a nonessential region of pJP4. Plasmid pRO101 was transferred by conjugation to several Pseudomonas strains and to A. eutrophus AEO106, a cured isolate of JMP134. AEO106(pRO101) and some Pseudomonas transconjugants grew on TFD. Transconjugants with a chromosomally encoded phenol hydroxylase also degraded phenoxyacetic acid (PAA) in the presence of an inducer of the TFD pathway, namely, TFD or 3-chlorobenzoate. A mutant of one such phenol-degrading strain, Pseudomonas putida PPO300(pRO101), grew on PAA as the sole carbon source in the absence of inducer. This isolate carried a mutant plasmid, designated pRO103, derived from pRO101 through the deletion of a 3.9-kilobase DNA fragment. Plasmid pRO103 constitutively expressed the TFD pathway, and this allowed the metabolism of PAA in the absence of the inducer, TFD. Complementation of pRO103 in trans by a DNA fragment corresponding to the fragment deleted in pRO101 indicates that a negative control-regulatory gene (tfdR) is located on the BamHI E fragment of pRO101. Other subcloning experiments resulted in the cloning of the tfdA monooxygenase gene on a 3.5-kilobase fragment derived from pRO101. This subclone, in the absence of other pRO101 DNA, constitutively expressed the tfdA gene and allowed PPO300 to grow on PAA. Preliminary evidence suggests that the monooxygenase activity encoded by this DNA fragment is feedback-inhibited by phenols. (+info)
Activity of agricultural chemicals to modify mitomycin C induced growth inhibition of Bacillus subtilis in the rec assay.
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Rec assay of agricultural chemicals, MCPA-E, MCPA, CNP and PCNB was conducted. It was found that MCPA-E and MCPA accelerated the growth-inhibition originally induced by Mitomycin C in the rec- strain. (+info)
Risk of malignant lymphoma in Swedish agricultural and forestry workers.
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The risk of malignant lymphoma after possible exposure to phenoxy acid herbicides was studied in 354,620 Swedish men who, according to a national census in 1960, were employed in agriculture or forestry. The cohort was divided into subcohorts according to assumed exposure and compared with 1,725,645 Swedish men having other economic activities. All were followed up in the Cancer-Environment Register between 1961 and 1979. Non-Hodgkin lymphoma was found in 861 men in the study cohort. The relative risk was not significantly increased in any subcohort, did not differ significantly between the subcohorts, and showed no time related increase in the total cohort or any subcohort. Hodgkin's disease was found in 355 men in the study cohort. Relative risks significantly higher than unity were found among fur farming and silviculture workers where the relative risks were 4.45 and 2.26, respectively. All five cases in the former group were engaged in mink farming. A time related rising trend in relative risk was found in the silviculture subcohort. Elsewhere the relative risk did not diverge from unity and no time related trend was discernible. (+info)
A double-blind comparison of the effects of hydrochlorothiazide and tienylic acid (a diuretic with uricosuric properties) in hypertension.
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1. A double-blind comparison of the effect of tienylic acid and hydrochlorothiazide on blood pressure was made in patients with moderate hypertension. 2. The antihypertensive effect of 500 mg tienylic acid was comparable to 100 mg hydrochlorothiazide; mean decrease in supine blood pressure after 6 weeks treatment was 20/12 mmHg with tienylic acid and 17/9 mmHg with hydrochlorothiazide. Onset of antihypertensive action was within 1 week and was associated with significant weight loss. 3. Tienylic acid caused a marked decrease in serum uric acid to a mean of 0.18 mmol/1 (n = 11, P less than 0.001), this persisted through the treatment period and returned to placebo values 1 week after treatment ceased. Some patients had uric acid crystaluria and some had post-treatment uric acid levels higher than on placebo. 4. Tineylic acid and hydrochlorothiazide caused mild hypokalemia and alkalosis with proportional decrease in plasma chloride. 5. Blood urea and serum creatinine rose with both drugs and there was an unimportant decline in plasma sodium. 6. Tienylic acid is an effective antihypertensive agent with powerful uricosuric action and appears relatively free of side effects. Further studies are necessary to determine optimal dosage regimes and long term safety. (+info)
Comparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone.
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The antihypertensive properties of the new diuretic tienilic acid were investigated. Thirteen previously untreated hypertensive patients took part in a double-blind crossover study in which 30 days' treatment with tienilic acid 250 mg, bendrofluazide 5 mg, and spironolactone 100 mg were compared. Bendrofluazide caused the greatest natriuresis on the first treatment day and the most rapid fall in blood pressure. The ultimate antihypertensive effect of all three drugs was similar. Tienilic acid caused a noticeable reduction in serum urate concentrations and a rise in urate clearance, in contrast to the other two agents, which caused slight urate retention. Tienilic acid and bendrofluazide caused falls and spironolactone a rise in plasma potassium concentrations. No untoward effects were seen from any of the drugs. It is concluded that tienilic acid is a moderately potent diuretic that lowers plasma urate concentrations. It may be the drug of first choice for hypertensive patients who already have gout or are likely to develop it when taking thiazide diuretics. (+info)
Extrapolation of biodegradation results to groundwater aquifers: reductive dehalogenation of aromatic compounds.
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The reductive biodegradation of a variety of haloaromatic substrates was monitored in samples from two sites within a shallow anoxic aquifer and was compared with freshwater sediment and sewage sludge. The metabolic capacity existing in methane-producing aquifer material was very similar to that in sediment in that three of four chlorobenzoates, five of seven chlorophenols, and one of two chlorophenoxyacetate herbicides were reductively dehalogenated in both types of incubations. The 2,4-dichlorophenoxyacetate was first converted to a dichlorophenol before dehalogenation occurred. Sewage sludge microorganisms dehalogenated four of seven chlorophenols tested and degraded both phenoxyacetate herbicides by first converting them to the corresponding chlorophenols, but the microorganisms did not transform the chlorobenzoates. In general, the same suite of initial metabolites were produced from a test substrate in all types of samples, as confirmed by cochromatography of the intermediates with authentic material. Aquifer microbiota from a sulfate-reducing site was unable to significantly degrade any of the haloaromatic substrates tested. Biological removal of the sulfate in samples from this site permitted dehalogenation of a model substrate, while stimulation of methanogenesis without removal of sulfate did not. These results demonstrate that dehalogenating microorganisms were present at this site but that their activity was at least partially inhibited by the high sulfate levels. (+info)
Anaerobic degradation of veratrylglycerol-beta-guaiacyl ether and guaiacoxyacetic acid by mixed rumen bacteria.
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Veratrylglycerol-beta-guaiacyl ether (0.2 g/liter), a lignin model compound, was found to be degraded by mixed rumen bacteria in a yeast extract medium under strictly anaerobic conditions to the extent of 19% within 24 h. Guaiacoxyacetic acid, 2-(o-methoxyphenoxy)ethanol, vanillic acid, and vanillin were detected as degradation products of veratrylglycerol-beta-guaiacyl ether by thin-layer chromatography, gas chromatography, and gas chromatography-mass spectrometry. Guaiacoxyacetic acid (0.25 g/liter), when added into the medium as a substrate, was entirely degraded within 36 h, resulting in the formation of phenoxyacetic acid, guaiacol, and phenol. These results suggest that the beta-arylether bond, an important intermonomer linkage in lignin, can be cleaved completely by these rumen anaerobes. (+info)