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Biomedical subjects

I A MacDonald

Publications and source records attributed to I A MacDonald.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effect of intravenous infusion of adrenaline on the cardiovascular responses to distal body subatmospheric pressure in man.

1. On two separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline [0.27 nmol (50 ng) min-1 kg-1] or saline (154 mmol/l NaCl), plus ascorbic acid (5.68 mmol/l), over 30 min. 2. On each occasion, the subjects were exposed to distal body subatmospheric pressure (DBSP), 0 to 50 mmHg (0 to 6.65 kPa) in 10 mmHg (1.33 kPa) steps, before infusion, during the final 15 min of the infusion, and at 15 min and 30 min after the cessation of the infusion. 3. Venous adrenaline concentrations of 2.85 +/- 0.22 nmol/l were achieved during the adrenaline infusion, compared with 0.49 +/- 0.07 nmol/l during the saline infusion (P less than 0.001). At 15 min and at 30 min after cessation of the adrenaline infusion, venous adrenaline concentrations had fallen to levels similar to those achieved after the cessation of the saline infusion. 4. Heart rate rose significantly from 58 +/- 4 beats/min to 67 +/- 4 beats/min during the adrenaline infusion (P less than 0.05), but there was no further significant change in response to 50 mmHg (6.65 kPa) DBSP. At 30 min after the cessation of the adrenaline infusion, heart rate rose from 60 +/- 4 beats/min to 78 +/- 7 beats/min in response to 50 mmHg DBSP. This increase was significantly greater than that observed before the adrenaline infusion [58 +/- 4 beats/min to 69 +/- 7 beats/min during 50 mmHg (6.65 kPa) DBSP; P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The effect of underfeeding on the physiological response to food ingestion in normal weight women.

1. The thermogenic, cardiovascular and metabolic responses to the ingestion of a 30 kJ/kg body-weight test meal were studied in six normal weight, female subjects before and after a 7 d period of underfeeding at 60 kJ/kg ideal body-weight per d. 2. With underfeeding there were decreases in body-weight, plasma insulin and 3,5,3'-triiodothyronine concentrations, resting metabolic rate and respiratory exchange ratio, with increased blood ketone levels. Baseline 'arterialized' venous plasma noradrenaline and adrenaline concentrations were not affected by underfeeding. 3. Ingestion of the test meal caused similar increases in heart rate and calf blood flow and changes in blood pressure in the fed and underfed states. There was a greater glycaemic response to the test meal in the underfed state compared with the fed state although the rise in plasma insulin concentration was similar and ketogenesis was suppressed. The increases in metabolic rate and plasma noradrenaline concentrations following the test meal were similar in the fed and underfed states. 4. Although the period of underfeeding in the present study led to considerable metabolic adaptation, and some alteration in physiological responses to ingestion of a test meal, there was no evidence that there were associated changes in sympathetic nervous system activation.

3-Hydroxybutyric Acid↗
PubMed1988

Abnormal thermoregulation in diabetic autonomic neuropathy.

Hypothermia has been reported to be more common in diabetic people than in nondiabetic people, and we have investigated the possibility that autonomic neuropathy may be associated with disordered thermoregulation. After an overnight fast and maintenance of normoglycemia, 12 insulin-treated diabetic patients with and 11 without neuropathy and 12 nondiabetic control subjects, all less than 55 yr, were subjected to external cooling by perfusing water at 16 degrees C through a liquid-conditioned coverall for less than or equal to 45 min. Patients with autonomic neuropathy had impaired vasoconstriction to cooling, particularly in the foot, calf, and forearm. Core temperature rose by 0.2 degrees C in control subjects and by 0.15 degrees C in patients with diabetes but no neuropathy. In contrast, group mean core temperature was unchanged in those with autonomic neuropathy and fell in 3 subjects (P less than .001). Cooling caused shivering in 6 patients with diabetic autonomic neuropathy, but not in those with neuropathy or control subjects (P less than .05). Baseline metabolic rates were similar in all three groups, but the increase after cooling was significantly greater among those who shivered (P less than .05-.02). Thus, young diabetic patients with autonomic neuropathy have impaired thermoregulation to a relatively short period of external cooling, even during metabolic stability, which may predispose to hypothermia.

Adult↗
PubMed1986

The influence of streptozotocin-induced diabetes mellitus on fluid and electrolyte handling in rats.

Intakes and urine outputs of fluid and electrolytes were measured daily in rats before, and for 3 weeks after, induction of diabetes by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg); control animals received saline. Water intakes and urine outputs were increased on and after the first day after injection with STZ; after a transient period of negative water balance, fluid intakes and urine outputs increased in parallel. Food intake was reduced for the first 3 days after injection of STZ but thereafter there was a steady increase. On the final experimental day, the food intake of the diabetic group was 60% greater than that of the control group. Urinary electrolyte excretion was increased after injection of STZ; at the end of the experiment, the increase in urinary sodium excretion was similar to the increase in intake but the increase in urinary potassium excretion was less. On day 21 after injection of STZ plasma sodium concentration and packed cell volume were significantly reduced in the diabetic group but plasma potassium concentration was not. There was a difference between the measured osmolality and the calculated osmolarity of the plasma of the diabetic animals which was not seen in the controls. This difference was not due to pseudohyponatraemia, but was probably due to the presence of unidentified solutes, since there was a significant gap between the urinary osmolal and osmolar excretion in the diabetic animals that was not present in the control animals.

Animals↗
PubMed1986

Withdrawal of salt supplementation from adrenalectomized Wistar rats distinguishes between those animals with, and those without, adrenocortical insufficiency.

The effects of replacing a 1% NaCl drinking solution with Na+-free water for 2 days on body weight and fluid and electrolyte balances were studied in adrenalectomized and sham-operated rats. Eight weeks after operation, after the animals had been drinking Na+-free water for 2 days, some adrenalectomized animals (about 75%; designated group experienced body weight losses which were outside the 99% confidence limits for the sham-operated rats (-9.2 to +5.3 g) whereas the remainder (designated group 2) were indistinguishable from the controls. The body weight loss in group 1 was associated with negative fluid, Na+ and K+ balances. In group 2 rats, fluid balance was maintained as well as in the sham-operated rats, but their handling of Na+ and K+ was different. In a separate experiment, plasma aldosterone, corticosterone, catecholamine and solute concentrations were measured in adrenalectomized rats from groups 1 and 2 (selected on the basis of body weight loss whilst drinking Na+-free water) and sham-operated rats, after drinking Na+-free water for 2 days. In group 1 animals, plasma aldosterone levels were unmeasurable and corticosterone was extremely low (less than 5% of controls). In group 2, aldosterone was measurable but low, and corticosterone was higher than in group 1 but lower than in sham-operated rats. In line with these findings, animals in group 1, but not those in group 2, were hyponatraemic and hyperkalaemic. These results are consistent with the activation of latent adrenocortical tissue in the group 2 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Insufficiency↗
PubMed1985

The effect of adrenaline upon cardiovascular and metabolic functions in man.

On three separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline, 50 ng min-1 kg-1 (high A), adrenaline, 10 ng min-1 kg-1 (low A) or sodium chloride solution (saline: 154 mmol of NaCl/l) plus ascorbic acid, 1 mg/ml (control), over 30 min. Venous adrenaline concentrations of 2.19 +/- 0.15 nmol/l, 0.73 +/- 0.08 nmol/l and 0.15 +/- 0.03 nmol/l were achieved during the high A, low A and control infusions respectively. Heart rate rose significantly by 19 +/- 3 beats/min (high A) and by 6 +/- 1 beats/min (low A). Heart rate remained significantly elevated 30 min after cessation of the high A infusion, despite venous plasma adrenaline concentration having fallen to control levels. The diastolic blood pressure fell during the high A and low A infusions, but the systolic blood pressure rose only during the high A infusion. Vasodilatation occurred in the calf vascular bed during both high A and low A infusions. The changes in hand blood flow and hand vascular resistance were not statistically significant, although there was a tendency to vasoconstriction during the infusion of adrenaline. Metabolic rate rose significantly by 23.5 +/- 1.8% (high A) and by 11.8 +/- 1.6% (low A). Metabolic rate remained elevated between 15 and 30 min after termination of the high A infusion. There was an initial transient increase in respiratory exchange ratio (RER) during the adrenaline infusions. During the later stages of the adrenaline infusions and after their cessation, RER fell, probably reflecting increased fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

The influence of environmental temperature upon the thermoregulatory responses to ethanol in man.

Ten healthy male subjects ingested ethanol (BP; 0.5 g/kg body weight) after an overnight fast, on two separate occasions, at environmental temperatures of either 21 degrees C or 30 degrees C. The mean maximal fall in deep body temperature was not significantly different on the two occasions, being 0.18 degrees C and 0.17 degrees C respectively. Metabolic rates throughout the experiments at the two temperatures were not significantly different. The vasodilatation of the hand and forearm vascular beds after ethanol ingestion was markedly reduced at the lower environmental temperature. In three subjects who ingested a higher dose of ethanol (BP; 1.0 g/kg body weight) after an overnight fast, at an environmental temperature of 21 degrees C, the mean maximum fall in core temperature was 0.15 degrees C, which was not significantly different from the change seen after consumption of the lower dose of ethanol. It is likely that the failure of ethanol ingestion to provoke hypothermia at the lower environmental temperature was due to the attenuated vasodilatation observed under these conditions.

Adult↗
PubMed1984

Rutin-induced beta-glucosidase activity in Streptococcus faecium VGH-1 and Streptococcus sp. strain FRP-17 isolated from human feces: formation of the mutagen, quercetin, from rutin.

A fecal isolate, Streptococcus sp. strain FRP-17, and strain VGH-1 of Streptococcus faecium were shown to contain beta-glucosidases which converted rutin (quercetin-3-O-beta-D-glucose-alpha-L-rhamnose) to quercetin and were active against o-nitrophenyl-beta-D-glucose. The activity against rutin could be measured by increased mutagenicity in the Ames assay or visualized on thin-layer chromatography plates. In both organisms, the beta-glucosidase activities were inducible by the addition of rutin to the growth media. Several closely related strains of Streptococcus spp. lacked any beta-glucosidase activity. In cell preparations of the active organisms, activities with rutin and o-nitrophenyl-beta-D-glucose were optimal at pH 6.8 and could be enhanced by increasing the ionic strength of the assay system. At low ionic strengths, both quercetin and a new product (intermediate between the polarities of rutin and quercetin) were formed by the incubation of rutin with cell preparations of either active organism. This product disappeared with increased ionic strength, suggesting that it may be a reaction intermediate, quercetin-3-O-beta-D-glucose. These results suggest that the beta-glucosidase active against rutin and that active against o-nitrophenyl-beta-D-glucose are the same.

Bacterial Proteins↗
PubMed1983

Estimation of ursodeoxycholic acid in human and bear biles using Clostridium absonum 7 beta-hydroxysteroid dehydrogenase.

Ursodeoxycholic acid was estimated in bile samples from humans and wild North American black bears using 7 beta-hydroxysteroid dehydrogenase purified from Clostridium absonum by Procion Red affinity chromatography. The percentage ursodeoxycholic acid was calculated by two methods: (a) 7 beta-hydroxyl groups were quantified using 7 beta-hydroxysteroid dehydrogenase and 3 alpha-hydroxyl groups (total bile acids) were quantified using 3 alpha-hydroxysteroid dehydrogenase. The percentage ursodeoxycholic acid was calculated on the basis of [7 beta-hydroxyl groups]/[3 alpha-hydroxyl groups] X 100. (b) Bile was hydrolyzed with sodium hydroxide and subjected to thin-layer chromatography. Bands corresponding to cholic acid, chenodeoxycholic acid plus deoxycholic acid, and ursodeoxycholic acid were identified by the use of standards and Komarowsky's spray reagent. Total bile acids and total ursodeoxycholic acid were measured by elution of silica gel in unsprayed areas corresponding to the bile acid standards and quantification of the total bile acid in each eluate. Direct comparison of these methods validated the use of 7 beta-hydroxysteroid dehydrogenase in the estimation of ursodeoxycholic acid in the biles of black bears and of patients fed ursodeoxycholic acid for cholesterol gallstone dissolution. Relative percentages of ursodeoxycholic acid were 8-24% in four bears and 22 and 27% in the patients ingesting 500 and 750 mg ursodeoxycholic acid per day for 3 months, respectively. Predictably lower values were obtained in two control subjects and one patient ingesting 750 mg chenodeoxycholic acid per day for 3 months.

Animals↗
PubMed1983

Day-case dental anaesthesia. Evaluation of pre-operative sublingual buprenorphine.

Sixty patients undergoing day-case dental surgery were either given sublingual buprenorphine 0.2 mg or 0.4 mg or a buffered placebo 1 hour prior to general anaesthesia. Pre-operative anxiety was not allayed and there was no significant analgesia afforded by buprenorphine in the immediate postoperative period. The synthetic opiate depressed psychomotor function and both 0.2 mg and 0.4 mg buprenorphine yielded a significantly higher incidence of postoperative nausea and vomiting.

Adolescent↗
PubMed1982

Nitrite-induced volatile fecal mutagens: some preliminary studies.

Further studies are reported on the formation of volatile mutagens from normal human feces incubated with sodium nitrite at 37 degrees C. Volatile mutagens were detected using Ames' Salmonella typhimurium tester strain TA1535 on petrie plates inverted over samples in sealed containers. An optimal exposure period was shown to be approximately 24 hours. When plates inverted over samples were replaced periodically, mutagenicity during serial 24 hour or 48 hour periods could be measured. Mutagenicity was optimal during the second 24 hour period and the first 48 hour period with 0.6 M sodium nitrite, and in the first 24- and 48-hour period with 0.2 M sodium nitrite. Subsequent exposure periods showed decreasing mutagenicity with time. Because of the great differences in reactivity with nitrite in stools of healthy volunteers, the effect of mixing "high reacting" samples with "low reacting" samples were investigated. When "low reacting" samples were mixed with "high reacting" samples, a lower mutagenicity of the mixture was observed compared to a predicted "average" value. Autoclaving stool samples made very little difference in nitrite-induced mutagenicity and behavior in mixing experiments. Thus, fecal mutagens arise as a spontaneous chemical process involving nitrite ions and both dietary and flora factors may be important in their production or absence.

Adult↗
PubMed1982

Formation of ursodeoxycholic acid from chenodeoxycholic acid by a 7 beta-hydroxysteroid dehydrogenase-elaborating Eubacterium aerofaciens strain cocultured with 7 alpha-hydroxysteroid dehydrogenase-elaborating organisms.

A gram-positive, anaerobic, chain-forming, rod-shaped anaerobe (isolate G20-7) was isolated from normal human feces. This organism was identified by cellular morphology as well as fermentative and biochemical data as Eubacterium aerofaciens. When isolate G20-7 was grown in the presence of Bacteroides fragilis or Escherichia coli (or another 7 alpha-hydroxysteroid dehydrogenase producer) and chenodeoxycholic acid, ursodeoxycholic acid produced. Time course curves revealed that 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid produced by B. fragilis or E. coli or introduced into the medium as a pure substance was reduced by G20-7 specifically to ursodeoxycholic acid. The addition of glycine- and taurine-conjugated primary bile acids (chenodeoxycholic and cholic acids) and other bile acids to binary cultures of B. fragilis and G20-7 revealed that (i) both conjugates were hydrolyzed to give free bile acids, (ii) ursocholic acid (3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) was produced when conjugated (or free) cholic acid was the substrate, and (iii) the epimerization reaction was at least partially reversible. Corroborating these observations, an NADP-dependent 7 beta-hydroxysteroid dehydrogenase (reacting specifically with 7 beta-OH-groups) was demonstrated in cell-free preparations of isolate G20-7; production of the enzyme was optimal at between 12 and 18 h of growth. This enzyme, when measured in the oxidative direction, was active with ursodeoxycholic acid, ursocholic acid, and the taurine conjugate of ursodeoxycholic acid (but not with chenodeoxycholic, deoxycholic, or cholic acids) and displayed an optimal pH range of 9.8 to 10.2

Bacteroides fragilis↗
PubMed1981

Bile induction of 7 alpha- and 7 beta-hydroxysteroid dehydrogenases in Clostridium absonum.

Eight strains of Clostridium absonum grown in the presence of 4 . 10(-4) M deoxycholate contained both NADP-dependent 7 alpha- and 7 beta-hydroxysteroid dehydrogenase activities. In one strain studied in detail, significant amounts of NADP-dependent 7 alpha- and 7 beta-hydroxysteroid dehydrogenase and NAD-dependent 7 alpha-hydroxysteroid dehydrogenase activities were demonstrated only when cells were grown in the presence of deoxycholate or chenodeoxycholate, both optimal at 4 . 10(-4) M. When the bile salt was deleted from the medium, only a trace of 7 alpha-hydroxysteroid dehydrogenase was present and 7 beta-hydroxysteroid dehydrogenase was absent. Other bile salts including cholate, ursodeoxycholate and keto bile salts were less effective as inducers. Addition of cholate to medium already containing deoxycholate at a suboptimal concentration enhanced the induction, while addition of ursodeoxycholate suppressed the induction. Further enhancement of 7 alpha- and 7 beta-hydroxysteroid dehydrogenase could be obtained by additions of deoxycholate (up to a total of 6 . 10(-4) M) during the growth of the organisms (in log phase). As enzyme enhancement is blocked by addition of rifampicin to the medium, the authors conclude that the enzymes are bile salt-inducible. Growth curve studies revealed an optimal enzyme yield at a harvest time of approx. 6-9 h. We have preliminarily characterized several inducible enzyme components: an NADP-dependent 7 beta-hydroxysteroid dehydrogenase as well as both NAD- and NADP-dependent 7 alpha-hydroxysteroid dehydrogenases.

Chenodeoxycholic Acid↗
PubMed1981

Nitrite-induced volatile mutagens from normal human feces.

Volatile mutagens (putative carcinogens) were produced from normal human and animal feces upon incubation with sodium nitrite in saline at 37 C for 48 hours. The mutagens were detected by using Ames' Salmonella typhimurium tester strain TA1535 without microsomes, on plates inverted over samples in sealed containers. Mutagenicity was maximal at 0.2 to 0.6 M NaNO2 and at pH 6.2 to 6.8. Reversions per plate varied from approximately 30 to 450 (1.5 to 25 x background) within the normal human population. Sodium ascorbate and alpha-Tocopherol (at one-half [NaNO2]) each reduced the mutagenicity by approximately 30%. Two standard N-nitroso-compounds were mutagenic in the system. We propose that the mutagenicity in our system is probably caused by the formation of volatile N-nitroso-compounds and that addition of nitrite to human feces in vitro enhances a process that occurs in vivo.

Ascorbic Acid↗
PubMed1981

Hypoglycaemia, hypothermia and shivering in man.

1. The present experiments were designed to elucidate the reasons for the fall in central body temperature during hypoglycaemia. 2. The first experiment was carried out at a room temperature of 25 degrees C on 11 male subjects. Hypoglycaemia was induced by infusion of insulin. Heat production (calculated from respiratory gas exchange) rose from a baseline of 5.10 +/- 0.13 kJ/min (mean +/- SEM) to a peak of 6.25 +/- 0.21 kJ/min (P less than 0.001), but core temperature fell concurrently by 0.51 +/- 0.08 degrees C and skin temperature fell by 1.1 +/- 0.2 degrees C. The net heat loss was due to peripheral vasodilatation and sweating. 3. To determine the effect of insulin-induced hypoglycaemia on thermoregulation in a cool environment, the experiment was repeated at a room temperature of 18-19 degrees C on five of the subjects who had air blown over them until shivering was sustained. During this time heat production rose to 10.13 +/- 1.67 kJ/min, but core temperature remained constant. Shivering stopped as plasma glucose fell below 2.5 mmol/l during insulin infusion and the subjects said they no longer felt cold. 4. During hypoglycaemia in the cold peripheral vasodilatation and sweating occurred, skin temperature fell by up to 0.8 degrees C and core temperature fell below 35 degrees C, so subjects had to be rewarmed. 5. Recovery of plasma glucose after hypoglycaemia in the cold was impaired at low body temperatures, but shivering was restored within seconds when glucose was given intravenously.

Adult↗