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Biomedical subjects

C A Brown

Publications and source records attributed to C A Brown.

At least 127 records · Page 7Linked to original sources
PubMed1994

Effects of aging and dietary protein intake on uninephrectomized geriatric dogs.

Thirty-one clinically normal Cocker Spaniels, Miniature Schnauzers, and Doberman Pinschers (28 female, 3 male) 7 to 8 years old were uninephrectomized (month -2) to increase the risk of renal damage associated with reduction of renal mass. Two diets, differing principally in protein concentration, were used to test the hypothesis that high dietary protein intake causes renal damage in aging dogs. For 2 months after uninephrectomy, all dogs were fed diet A (18% protein). After glomerular filtration rate (GFR) was measured (month 0), 16 dogs were assigned to group A and were fed diet A for an additional 48 months. The other 15 dogs were assigned to group B, and were fed diet B (34% protein) for the subsequent 48 months. At 6-month intervals, GFR and urine protein-to-creatinine ratio (UP/C) were determined. At 48 months, terminal studies were done, survivors were euthanatized, and tissues were examined. Of 16 dogs in group A, 10 survived, compared with 13 of 15 in group B. Among survivors, a significant difference in GFR was not found between groups A and B, and decrease in GFR was not evident with time in either group. At 48 months, oral administration of casein caused minor acute effects on GFR and renal plasma flow in dogs of groups A and B. The UP/C values increased significantly (P = 0.001) from baseline values, but the increase was not progressive. The UP/C values were not affected by diet. Some dogs in both groups developed UP/C > 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Stimulation of insulin secretion by the imidazoline alpha 2-adrenoceptor antagonist efaroxan is mediated by a novel, stereoselective, binding site.

We have studied the stereospecificity of three responses mediated by the alpha 2-antagonist efaroxan in rat islets of Langerhans. alpha 2-Adrenergic inhibition of insulin secretion was relieved most effectively by the (+) enantiomer. In contrast, direct stimulation of insulin secretion and antagonism of the inhibitory effects of diazoxide were both preferentially mediated by the (-) enantiomer. Culture of islets in the presence of efaroxan resulted in loss of responsiveness to subsequent re-addition of the drug. On the basis of these results we propose the existence, in islets, of a novel 'non-adrenergic' binding site at which efaroxan acts as an agonist.

Adrenergic alpha-Antagonists↗
PubMed1993

Delayed hypersensitivity testing as a clinical measure of cell-mediated immunity in the cat.

The purposes of this study were to examine the cell-mediated immune response of the normal cat to the modified live feline viral rhinitis, calicivirus, and parvovirus (FVRCP) vaccine (Felocell CVR, Norden, Lincoln, NE), and to evaluate the intradermal skin test as a clinical measure of the immune response of cats. Vaccine and diluent were injected intradermally on the dorsal pinna of 34 normal adult cats. Skin thickness measurements, lymphocyte counts, and Concanavalin A mitogenesis indices were evaluated in 18 of these cats. Skin biopsies were obtained in 16 cats. In normal cats, the FVRCP vaccine induced a delayed hypersensitivity response characterized by a mononuclear infiltrate most pronounced at 72 h. Five cats with either feline leukemia (FeLV) or feline immunodeficiency virus (FIV) were tested and had a significantly reduced response to the skin test. The skin test provides a clinically useful method of evaluating immune function in cats and may be useful in development of a prognostic index.

Animals↗
PubMed1993

Nutrient intake by duration of ex-smoking in the Scottish Heart Health Study.

Information on current-, never- and ex-smokers (including duration of cessation) was obtained in a cross-sectional survey of risk factors for coronary heart disease (CHD), the Scottish Heart Health Study. Diet was also assessed by food frequency questionnaire in a total of 4265 men and 4770 women. Nutrient intakes were computed by sex and smoking group and, according to their diet, the ex-smokers were categorized as current- or never-smokers using discriminant analysis techniques. The current- and five ex-smoking groups differed negligibly in past smoking characteristics. Energy-adjusted intake of polyunsaturated fat, fibre and the antioxidant vitamins were lowest in current-smokers, and for men, intakes increased progressively with duration of ex-smoking to reach the level of never-smokers. In a similar manner, energy, sugar and alcohol decreased with duration of ex-smoking. Fewer trends were observable for women, and the diets of ex-smokers more immediately resembled that of never-smokers. Discriminant analysis for the combined nutrients correctly categorized 72 and 69% of male, and 66 and 65% of female current- and never-smokers respectively. By 4 years of smoking cessation the general dietary pattern of ex-smokers was similar to never-smokers for both sexes. Whether this represents a change in diet over time or a cohort effect is unclear, but the results do suggest that the apparent healthier diet of ex-smokers may contribute to their reduction in CHD risk compared with life-long current-smokers.

Adult↗
PubMed1993

Stimulation of insulin secretion by imidazoline compounds is not due to interaction with non-adrenoceptor idazoxan binding sites.

1. The potency of interaction of several imidazoline compounds with non-adrenoceptor idazoxan binding sites (NAIBS) in rat liver membranes was compared with their ability to alter insulin secretion from rat pancreatic islets. 2. NAIBS could be labelled specifically with [3H]-idazoxan in both rat liver membranes and in rat islet homogenates. Liver binding sites exhibited a KD for [3H]-idazoxan of 24 nM and a Bmax of 264 fmol mg-1 protein. 3. Binding of [3H]-idazoxan to NAIBS in rat liver membranes was displaced effectively by unlabelled idazoxan (IC50 0.1 microM) and by UK14304 (IC50 0.5 microM). However, two other imidazoline compounds efaroxan and RX821002, which are related in structure to idazoxan, were much less effective as displacers. 4. In insulin secretion experiments, the ATP-sensitive potassium channel agonist diazoxide (250 microM) was able to suppress the rise in insulin secretion induced by 20 mM glucose. Both efaroxan and RX821002 (100 microM) antagonized the inhibitory effect of diazoxide on glucose-induced insulin secretion. By contrast, neither idazoxan (100 microM) nor UK14304 (50 microM), was able to overcome significantly the inhibitory effect of diazoxide. 5. The ability of 100 microM efaroxan to antagonize the suppression of insulin secretion mediated by diazoxide, was not prevented by idazoxan (up to 100 microM) or by UK14304 (up to 50 microM). 6. The results indicate that the stimulatory effects of imidazoline compounds on insulin secretion are not due to interaction with NAIBS similar to those present in rat liver.

Adrenergic alpha-Agonists↗
PubMed1993

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080.

1. The imidazoline alpha 2-adrenoceptor antagonist, efaroxan, stimulates insulin secretion from rat isolated islets and antagonizes the ability of diazoxide to inhibit glucose-induced insulin secretion. These effects result from closure of ATP-sensitive potassium channels although the mechanisms involved have not been elucidated. 2. In the present work, we have examined the effects of a close structural analogue of efaroxan, RX801080, in rat isolated islets of Langerhans. RX801080 was found to be ineffective as a stimulator of insulin secretion and did not prevent the inhibition of insulin secretion mediated by diazoxide. 3. RX801080 acted as an antagonist of the actions of several imidazolines (efaroxan, phentolamine and midaglizole) in rat islets. It dose-dependently inhibited the ability of efaroxan to antagonize the effects of diazoxide in islets and also completely inhibited the direct stimulation of insulin secretion mediated by efaroxan. 4. RX801080 also antagonized the effects of the non-imidazoline, ATP-sensitive potassium channel blocker, glibenclamide, in rat islets. It inhibited both the capacity of glibenclamide to stimulate insulin secretion and the ability of glibenclamide to overcome the inhibitory effects of diazoxide in rat islets. 5. Antagonism of glibenclamide responses by RX801080 was not due to inhibition of binding of the sulphonylurea to its receptor on the pancreatic beta-cell. 6. The results suggest that imidazoline compounds and sulphonylureas interact with distinct binding sites on islet cells, but that these sites can interact functionally to control islet cell ATP-sensitive potassium channel activity and insulin secretion.

Adrenergic alpha-Antagonists↗
PubMed1993

Coffee and tea consumption and the prevalence of coronary heart disease in men and women: results from the Scottish Heart Health Study.

STUDY OBJECTIVES: The aim was to determine if there was a relationship between coffee or tea consumption and the prevalence of coronary heart disease in Scotland. DESIGN: The relationship between self reported coffee and tea consumption and the prevalence of coronary heart disease (history, symptoms, or electrocardiographic evidence) was investigated using multiple logistic regression analysis in the Scottish Heart Health Study (SHHS), a cross sectional study. SETTING: Twenty two Scottish districts were surveyed for the SHHS between 1984 and 1986. SUBJECTS: A total of 10,359 men and women aged 40-59 years were studied. MEASUREMENTS AND MAIN RESULTS: Of the 9740 subjects who were assigned a category, 21.8% (2122) were classified as having indications of coronary heart disease. Men and women were combined in the odds ratio analysis because they showed almost identical patterns in the prevalence of coronary heart disease across the coffee and tea quarters (grouped according to consumption). Those who did not drink coffee had a significantly higher (p < 0.05) prevalence of coronary heart disease than the three groups for coffee drinkers. Adjustments for risk factors including cigarette smoking, total blood cholesterol, and diastolic blood pressure did not remove the significance of the odds ratios. There was a positive dose-response effect between tea consumption and coronary heart disease which was removed after adjustment for various risk factors. CONCLUSIONS: These findings do not support a positive relationship between coffee or tea consumption and coronary heart disease in this British study where most coffee consumed is instant coffee.

Adult↗
PubMed1993

Prevalence of chronic cough and phlegm among male cigar and pipe smokers: results of the Scottish Heart Health Study.

BACKGROUND: Previous studies investigating the effect of cigar or pipe smoking on the occurrence of chronic cough and chronic phlegm have reported prevalences among cigar and pipe smokers lying between those of non-smokers and current cigarette smokers. This study uses data on previous cigarette consumption, current cigar or pipe consumption, and biochemical markers of smoking to provide a detailed analysis of chronic cough and chronic phlegm among cigar and pipe smokers. METHODS: A total of 10,359 men and women aged 40-59 years were sampled for the Scottish Heart Health Study between 1984 and 1986. Prevalence of chronic cough and chronic phlegm among male cigar and pipe smokers (non-cigarette smokers) was compared with those who had never smoked, between ex-smokers of cigarettes and those who had never smoked cigarettes, between cigar-only and pipe-only smokers, and by cigar or pipe consumption levels. RESULTS: In all, 463 ex-smokers of cigarettes and 154 who had never smoked cigarettes were cigar or pipe smokers; 1080 had never smoked any form of tobacco. Ex-cigarette smokers smoked and inhaled more than those who had never smoked cigarettes. Among the ex-cigarette smokers, cigar or pipe smokers had 1.63-1.71 times the prevalence of both chronic cough and chronic phlegm than those who had never smoked (1.31-1.36 among cigar only smokers; 2.23-2.84 among pipe only smokers). A strong positive dose-response effect was found between the prevalence of symptoms and cigar or pipe consumption. CONCLUSIONS: Cigar and pipe smokers have a higher prevalence of chronic cough and phlegm than those who have never smoked, and the difference is more marked in pipe-only smokers than in cigar-only smokers. Both categories show a positive dose-response effect. Among cigar and pipe smokers, ex-cigarette smokers have a higher prevalence of symptoms than those who have never smoked cigarettes, which may be because they inhale more or may be attributable to previous cigarette smoking.

Adult↗