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Biomedical subjects

A D Brown

Publications and source records attributed to A D Brown.

At least 19 recordsLinked to original sources

Dietary variability in Cebus apella in extreme habitats: evidence for adaptability.

The dietary composition of Cebus apella in two subtropical forest environments of Argentina reflects the seasonal availability of potential food resources. In the marginal areas of the geographical distribution of this species, different resources are used during periods of scarcity. A greater tendency to use leaves in the diet is observed in the northwest (El Rey National Park), where there is greater seasonal variation of fruit availability. In El Rey, where there are few potential resources, the diet is dominated by a few resources, notably bromeliads. Where the resources are more abundant and the availability is more constant throughout the years (Baritú and Iguazú National Parks), the monkeys exhibit a feeding behavior similar to that seen in tropical areas. This ability of the genus Cebus to exploit resources not accessible to other primate species is one of the reasons for its wide geographical distribution and its widespread existence in ecosystems marginally used by primates.

Adaptation, Biological

The Burch Colposuspension operation for stress urinary incontinence.

One hundred and thirteen patients with genuine stress incontinence were treated by a modified Burch Colposuspension after having failed an adequate trial with medical management. Three-quarters of patients were evaluated with pre-operative video-cystometry (video-C.M.G.) while a third underwent post-operative video-cystometry. Flow rates were generally lower after surgery with 3 of the 113 patients developing post-surgery bladder instability. Previous incontinence surgery and higher parity produced statistically a greater number of failures. The overall subjective success of the operation was 80% with another 12% improved at 2 years. A 5 year long-term questionnaire follow-up did not demonstrate marked changes in these figures. The operation itself carries a 16% incidence of significant early complications, while late complications totalled 23%, the latter being primarily minor conditions. Patients left hospital after an average of 10 days.

Adult

Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit.

In order to study noradrenaline-induced regulation of alpha- and beta-adrenoceptors, groups of male New Zealand White rabbits (n = 8) were treated with intravenous noradrenaline (0.09 mumol/kg x h) or ascorbate (0.1%) for 10 days via osmotic minipumps implanted in the femoral vein, and the number of cardiac, lung and lymphocyte beta-adrenoceptors as well as renal and platelet alpha 2-adrenoceptors were determined. 1. The mean arterial blood pressure, heart rate and catecholamine levels were measured before commencing, and after 24 h and 10 days infusion. Circulating noradrenaline concentrations were elevated approximately 6-fold at 24 h and were sustained at these levels after 10 days administration of noradrenaline. There were no significant alterations in the blood pressure while a significant decrease in the heart rate was observed at 24 h. 2. Alpha 2-adrenoceptor density was assessed using [3H]-yohimbine. A significant decrease in the number of alpha 2-adrenoceptors in the kidney was observed following the 10 days infusion with noradrenaline. This down-regulation was in marked contrast to the lack of alteration in platelet alpha 2-adrenoceptor number and the platelet alpha 2-adrenoceptor mediated aggregatory response. 3. The density of beta-adrenoceptors in lymphocytes, heart and lung were quantified using (-)[125I]iodocyanopindolol (ICYP). The noradrenaline infusions caused significant reductions in beta-adrenoceptor number in the heart and lung (containing predominantly beta 1-adrenoceptors) but not in lymphocytes (possessing mainly beta 2-adrenoceptors). The KD-values (pM) for ICYP binding to heart and lung were also significantly decreased in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines.

The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

Angiotensin-Converting Enzyme Inhibitors

Water stress plating hypersensitivity of yeasts: protective role of trehalose in Saccharomyces cerevisiae.

Water stress plating hypersensitivity was studied in two strains of Saccharomyces cerevisiae, one of them being a mutant incapable of accumulating trehalose to significant levels. The wild-type strain was grown in a defined medium with glucose, maltose or ethanol as carbon/energy source. In each case plating hypersensitivity was demonstrated and resistance to the stress developed in the second half of the exponential growth phase. Development of resistance was accompanied by accumulation of trehalose and was apparently unrelated to glycerol content which, under these conditions, was always low. A qualitatively similar trend was observed in the mutant grown on glucose but trehalose levels remained low and recovery of stress resistance was only slight. Dinitrophenol induced trehalose breakdown in resting yeast and simultaneously induced the onset of plating hypersensitivity. A negative correlation was demonstrated between trehalose content and 'plating discrepancy' (log colony count on 'normal' agar-log colony count on stressing agar) for both strains under all experimental conditions. The correlation held for trehalose contents up to about 50 mg (g dry yeast)-1, above which the yeasts were apparently fully resistant. Trehalose was evidently a more effective compatible solute, per mole, than glycerol.

Colony Count, Microbial

Protective action of SCH 12223 against experimentally induced gastric and intestinal lesions.

The gastrointestinal protective action of SCH 12223 [3-(n-butyl)-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one hydrate, sodium salt] against various noxious stimuli was characterized in rats. SCH 12223 inhibited the ethanol-induced gastric lesions when given p.o. (0.3-3 mg/kg) or i.v. (1 and 3 mg/kg). Indomethacin pretreatment (10 mg/kg p.o.) did not interfere with this effect. SCH 12223 was also active p.o. in five gastric erosion models: aspirin (1-10 mg/kg), aspirin + acid (1-30 mg/kg), indomethacin (1-10 mg/kg), stress (1 and 3 mg/kg) and reserpine (0.3-10 mg/kg)-induced erosions. The compound lacked antisecretory activity in the pylorus-ligated rats (10 mg/kg p.o.) but increased total gastric mucus (N-acetylneuraminic acid measurements) (1-10 mg/kg p.o.). SCH 12223 (10 and 30 mg/kg p.o.) attenuated intestinal lesions provoked by indomethacin (20 mg/kg p.o. or s.c.) and the protected animals showed better weight gain and food intake than controls. In a 38-day study, SCH 12223 also improved survival from indomethacin lethality (6 of 16 vs. 16 of 16 in the control, P less than .05). The protection cannot be attributed to changes in biliary excretion and plasma levels of indomethacin. We conclude that SCH 12223 is a unique agent which protects both gastric and intestinal epithelia from noxious stimuli, a feature shared by prostaglandins.

Administration, Oral

Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women.

The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double-blind prospective trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo. Patients were assessed subjectively and objectively before and after treatment by 7-day bladder charts, urethral pressure profiles (UPP), the Urilos nappy test, vaginal cytology and hormone assays (plasma oestrogens and gonadotrophins). There was no statistical difference in the subjective response to treatment between the two groups. After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen-treated patients that approached statistical significance but, because of a marked response in the placebo group, this difference was not significant after 3 months of treatment. There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens. In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited.

Aged

An objective assessment of physiotherapy for female genuine stress incontinence.

Sixty women with genuine stress incontinence were consecutively assigned to one of four physiotherapy groups who were treated for 6 weeks by either (1) pelvic floor exercises (PFE) in hospital; (2) PFE and faradism; (3) PFE and interferential therapy; (4) PFE at home. Assessment before and after treatment was by 7-day bladder charts, urethral pressure profiles and perineometry. Approximately two-thirds of the hospital-treated patients (groups 1, 2 and 3) experienced marked or moderate subjective improvement and at 6 months, 27% were dry or almost dry. There was little difference in outcome between groups 1, 2 and 3 but hospital-based therapy was more effective than home treatment. Statistical analyses showed that there were significant improvements in the objective indices measured in the 45 hospital-treated patients. Successful treatment was more likely in younger patients, in those with lesser degrees of genuine stress incontinence and those who had had no previous pelvic floor surgery.

Adult

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

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