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Biomedical subjects

A D Brown

Publications and source records attributed to A D Brown.

At least 55 records · Page 3Linked to original sources

Water stress plating hypersensitivity of yeasts.

Saccharomyces cerevisiae, when growing exponentially in batch culture, passed through a phase in which, on average, one cell in 10(4) survived plating onto a low water activity (aw) agar medium. Stationary phase cultures were resistant as were all other species tested, with the exception of Candida krusei. In continuous culture, S. cerevisiae was more resistant at low than at high dilution rates. Plating at low aw was lethal to those cells that were not protected by an adequate content of compatible solute. In naturally resistant yeasts and in S. cerevisiae that had been exposed to an adaptation process, the compatible solute was one or more types of polyhydric alcohol. Resistance in stationary phase was attributable to a different cause.

Cell Survival↗

Inhibitory effect of captopril on renal responses to frusemide in sodium-restricted rats.

Indomethacin (10 mg kg-1 orally) caused a moderate inhibition of the renal responses to frusemide (30 mg kg-1 orally) only in Na+-deficient rats, suggesting that renal prostaglandins (PG) are necessary for optimal effects of frusemide during Na+ restriction. Captopril (1, 3 and 10 mg kg-1 orally) also inhibited frusemide-induced diuresis and natriuresis in Na+-deficient rats; the large effect of captopril at 10 mg kg-1 was accompanied by arterial hypotension. In normal rats, captopril did not disturb blood pressure or affect the renal effects of frusemide. By comparison, minoxidil (10 and 20 mg kg-1 orally) caused hypotension and reduced the natriuretic effects of frusemide in both normal and low-Na+ states. Since circulating angiotensin II (AII) is a stimulus for PG synthesis during Na+ restriction, it is suggested that captopril may impair the renal responses to frusemide through hormonal and haemodynamic changes resulting from inhibition of A II formation.

Animals↗

Effects of a gastric antisecretory-cytoprotectant 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (Sch 28 080) on cysteamine, reserpine and stress ulcers in rats.

Prostaglandin E2 and carbenoxolone, putative cytoprotective agents, were tested in cysteamine, reserpine and stress ulcers in rats. In cysteamine-induced duodenal ulcer, PGE2 was inactive at 0.1 and 0.5 mg/kg p.o.; carbenoxolone at 100 mg/kg p.o. decreased the incidence but not the severity of the ulcer. PGE2 at 5.0 mg/kg p.o. and carbenoxolone at 300 mg/kg p.o. showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion. PGE2 (0.1 and 0.3 mg/kg p.o.) was inactive and carbenoxolone (100 and 300 mg/kg p.o.) further aggravated the gastric ulceration caused by reserpine or cold-restraint stress. In contrast, atropine (3 and 10 mg/kg p.o.) and cimetidine (30, 100 and 300 mg/kg p.o.) were active in all three ulcer models. But the results with cimetidine in stress ulcer were somewhat variable. 2-methyl-8-(phenylmethoxy) imidazo [1,2-a] pyridine-3-acetonitrile (Sch 28 080), a novel structure with both cytoprotective and antisecretory activity, was highly efficacious in cysteamine, reserpine and stress ulcers (1-30 mg/kg p.o.), which was presumably adequately accounted for by its potent antisecretory activity. It is concluded that cysteamine, reserpine and stress ulcers may not be appropriate models for testing the potential antiulcer effect of primarily cytoprotective compounds.

Animals↗

Posterior pubo-urethral ligaments in normal and genuine stress incontinent women.

Specimens of the posterior pubo-urethral ligament were taken from 10 continent females (7 at post mortem and 3 at gynaecological surgery) and from 9 genuine stress incontinent patients. They were examined and compared using light and electron microscopy and neuro-histochemistry. The morphology of all specimens was similar in that they contained dense connective tissue elements enclosing smooth muscle bundles which were associated with numerous nerves, the enzyme content and fine structure of which were similar to those believed to represent cholinergic autonomic nerves. There was no difference in the morphology, histochemistry and fine structure of the specimens of the ligaments from the control and incontinent patients. Therefore, it is suggested that altered morphology of the posterior pubo-urethral ligaments is unlikely to be an etiological factor in genuine stress incontinence. It is postulated that the ligaments may play a role in stabilising the proximal urethra or assist in bladder-neck opening during voiding.

Adult↗

Effect of captopril on pre-existing and aminonucleoside-induced proteinuria in spontaneously hypertensive rats.

Proteinuria is a side effect of captopril treatment in hypertensive patients. The possibility of reproducing the same renal abnormality with captopril was examined in SHR. Oral administration of captopril at 100 mg/kg for 14 days failed to aggravate proteinuria pre-existing in SHR. Also, captopril treatment failed to potentiate or facilitate development of massive proteinuria invoked by puromycin aminonucleoside in SHR. Captopril had little or no demonstrable effects on serum electrolyte concentrations, excretion of urine, sodium and potassium, endogenous creatinine clearance, body weight, and food and water consumption. However, ketone bodies were consistently present in urine and several lethalities occurred during multiple dosing of captopril in SHR.

Animals↗

Quantifying female incontinence with particular reference to the Urilos System.

An assessment of the Urilos System for quantifying urinary incontinence is presented. There was approximate reproducibility of urine loss measurements between nappies in the same pack but under- and over-recordings of up to 25 and 23%, respectively, were observed; when packs of nappies were compared there were differences of up to 68%. Thus, the Urilos System is not, as yet, sufficiently reliable for quantifying incontinence. Other methods of measuring incontinence objectively are discussed and the use of the daily bladder chart is commended.

Equipment and Supplies↗

The salt relations of Dunaliella. Further observations on glycerol production and its regulation.

Dunaliella tertiolecta (marine) and D. viridis (halophilic) were each trained by serial transfer to grow at salt concentrations previously regarded as the other's domain. D. viridis then had a salt optimum at 1.0-1.5 M sodium chloride whereas that for D. tertiolecta was less than 0-2 M. Nevertheless D. tertiolecta grew faster than the halophil at all salt concentrations up to 3.5 M, the highest at which they were compared. Both species accumulate glycerol, which is necessary for growth at elevated salinities and which responds in its content to water activity (aw) rather than specifically to salt concentration. Variation in glycerol content is a metabolic process which occurs in the dark from accumulated starch as well as photosynthetically. Regulation of glycerol content by aw does not require protein synthesis. The NADP-specific glycerol dehydrogenase of each of the algae is likely to be directly involved in the regulation of glycerol content. Kinetic studies, together with those described in an earlier publication, show that the enzyme has regulatory properties and that both glycerol and dihydroxyacetone act as effectors as well as reactants. A mechanism of the reaction is tentatively proposed.

Alcohol Oxidoreductases↗

Renal pharmacology of netilmicin.

Netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was studied for its effects on kidney function and mechanisms by which it is handled by the kidneys. Measurements of glomerular filtration rate (GFR) and urinalysis in chronic rat studies indicated that the nephrotoxicity of netilmicin was remarkably less than that of gentamicin. Gentamicin caused a dose-related reduction in GFR in association with glucosuria and elevated fractional excretion of K(+). By contrast, high doses of netilmicin produced only slight reduction in GFR with increased fractional excretion of K(+) but without glucosuria. In separate experiments, rats were shown to excrete 71 to 90% of netilmicin or gentamicin in 24 h after daily intramuscular administration of doses of 20 or 40 mg/kg for 4 days. In acute experiments on anesthetized dogs, GFR and renal plasma flow were unaffected at serum levels of 11.0 +/- 0.6 mug/ml maintained by constant infusion of netilmicin for 5 h. The renal clearance of netilmicin was significantly correlated with GFR. The urinary output of netilmicin was 80.0 +/- 4.2% of the infusion rate and was independent of urine flow over the range of 0.04 to 0.33 ml/kg per min. Preferential accumulation of netilmicin occurred in the renal cortex; the cortex-serum and medulla-serum ratios were 9.9 +/- 1.2 and 4.2 +/- 0.6, respectively. In addition, the extraction ratio of netilmicin, which was lower than that of inulin, suggested that netilmicin reabsorption occurs in the proximal tubule and results in cortical accumulation. It is concluded that netilmicin, like gentamicin, is excreted by the dog kidney by glomerular filtration plus limited reabsorption. However, the new drug is characterized by low intrinsic nephrotoxicity in rats.

Animals↗

Postmenopausal urinary problems.

Detailed objective assessment of urinary symptoms provides information from which satisfactory treatment can be given. The fundamental investigations are history and clinical examination, endoscopy and two-channel cystometry (using several provocative tests). Detrusor dysfunction is a commoner cause of urinary symptoms than is generally realized and it cannot be diagnosed easily on clinical assessment. Initial treatment of all urinary problems should be conservative as the majority of patients benefit, and surgery should be carried out only after careful selection of patients and operative techniques.

Adult↗

Microbial water relations. Effects of solute concentration on the respiratory activity of sugar-tolerant and non-tolerant yeasts.

The respiratory activity of the sugar-tolerant (osmophilic) yeast, Saccharomyces rouxii, and the non-tolerant species, Sacchromyces cerevisiae, were compared after growth in a complex basal medium, the medium supplemented with polyethylene glycol (mol. wt 200) to give a water activity of 0-95, and the medium supplemented with glucose (24 and 36%, w/v). The properties compared were Qo2 (glucose), NADH oxidase activity of isolated mitochondrial fractions, and cytochrome content. When grown in the basal medium S. cerevisiae was somewhat more active than S. rouxii by all criteria. Growth in the media supplemented were high glucose concentrations produced catabolite repression of respiration in S. cerevisiae but not in S. rouxii. The implications of this difference for polyol biosynthesis and the water relations of the sugar-tolerant species are discussed.

Cytochromes↗

Microbial water relations: features of the intracellular composition of sugar-tolerant yeasts.

Several factors contributed to differences in intracellular composition between sugar-tolerant (osmophilic) and nontolerant species of yeast. One such factor was the difference in accumulation of those nonelectrolytes whose uptake was not dominated by vigorous metabolism. In such cases (lactose and glycerol), the sugar-tolerant species had a much lower capacity for the solute than did the nontolerant species. Sucrose uptake was consistently different between all sugar-tolerant strains on the one hand and all nontolerant strains on the other. The difference was attributable in part to metabolism of sucrose by the nontolerant yeasts. The major difference between the two types of yeast, however, was the presence of one or more polyhydric alcohols at high concentrations within each of the sugar-tolerant strains but none of the nontolerant strains. In most cases the major polyol was arabitol. The solute concentration (and, hence, water availability) of the growth medium affected both the amount of arabitol produced by Saccharomyces rouxii and the proportion retained by the yeast after brief washing with water at 0 C. When the yeast was suspended in a buffer at 30 C, the polyol leaked out at a slow, constant, reproducible rate. The polyene antibiotic amphotericin B caused rapid release of polyol by the yeast, the rate being proportional to amphotericin concentration. Contact of the yeast with glucose (1 mM) caused an extremely rapid ejection of polyol which lasted less than 40 s. Some implications of these results are discussed, as is the role of the polyol as a compatible solute in determining the water relations of the yeast.

Alcohols↗