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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 307 records · Page 17Linked to original sources

Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism.

Corticotropin-releasing factor (CRF) injected into the brains of rats produces hyperglycemia and an increase in plasma concentrations of glucagon, epinephrine, and norepinephrine. Neither hypophysectomy nor adrenalectomy prevents CRF-induced hyperglycemia. However, a role of adrenal epinephrine release in mediating CRF-induced hyperglycemia is supported by the finding that the central nervous system-selective somatostatin analog, desAA1,2,4,5,12,13-[D-Trp8]somatostatin, totally prevents the elevation of plasma epinephrine and suppresses the rise of plasma glucose but does not alter the increase in plasma norepinephrine induced by CRF. Pretreatment with the ganglionic blocker chlorisondamine completely prevents the CRF-induced rises in plasma glucose, epinephrine, and norepinephrine. These results demonstrate that CRF acts within the brain to stimulate sympathetic outflow, which results in the development of hyperglycemia. In contrast to other peptides that act within the central nervous system, e.g. bombesin, TRF, and beta-endorphin, whose hyperglycemic actions depend exclusively on adrenal epinephrine secretion, CRF-induced hyperglycemia is secondary to the enhanced secretion of both epinephrine and norepinephrine.

Animals↗

Central and peripheral nervous system complications.

Symptomatic neuropathy is a common manifestation of diabetes mellitus, and sensory, motor, or autonomic symptoms occur in approximately 10% of all diabetic patients. Animal models may be useful to study the metabolic and electrophysiologic abnormalities peculiar to diabetic neuropathy. Genetic animal models, including the Chinese hamster, ob/ob mouse, db/db mouse, BB-wistar rat, and SSDR rat or chemically induced or nutritional models of diabetes mellitus provide the potential to use animals to study human neuropathy; however, to date, few characteristics of human diabetic neuropathy have been clearly demonstrated in any of these animal models. Better characterization of the neuropathy of existing animal models with emphasis on evaluation over long periods of time is recommended. These studies should include a cross-disciplinary approach using biochemical, electrophysiologic and morphologic techniques. Specific future approaches to study diabetic neuropathy using chemical models is outlined in this chapter.

Alloxan↗

Helminth and arthropod parasites of blesbok, damaliscus dorcas phillipsi, and of bontebok, Damaliscus dorcas dorcas.

The helminth burdens of 8 blesbok shot in the north-eastern Orange Free State, 8 from the eastern Cape Province, 28 from the eastern Transvaal and 3 from the central Transvaal were determined. In addition, the arthropod burdens of 11 of these animals were ascertained. Twenty-one nematode species, 2 cestode species, 6 ixodid ticks, 2 lice and the larvae of 5 oestrid flies were recovered. Three of the nematode species, 2 of the oestrid flies and 4 of the tick species had apparently not previously been recovered from blesbok. Thirty-one bontebok culled in the south-western Cape Province were examined for endoparasites and 8 of these animals were also examined for ectoparasites. They harboured 12 nematode species, 3 ixodid ticks, a louse and the larvae of an oestrid fly. In common with some of the blesbok they were parasitized by Dictyocaulus magnus, Longistrongylus curvispiculum, Trichostrongylus axei, Nematodirus spathiger and the larvae of a large Gedoelstia sp. Five of the nematode species, the larvae of the oestrid fly species and the 3 ixodid tick species had not previously been recorded from bontebok.

Animals↗

Reduction in basal ganglia and substantia nigra substance P levels in Huntington's disease.

Substance P (SP) levels were determined by radioimmunoassay (RIA) in several regions of post-mortem brain of controls and Huntington's disease (HD) patients. In controls, highest SP levels were found in basal ganglia, substantia nigra and hypothalamus. Nigral pars reticulata contained 3--4-fold higher levels than pars compacta. In HD, SP levels were reduced in all basal ganglia and substantia nigra. The reductions ranged from 48% in caudate nucleus to over 90% in nigral pars reticulata. There were no changes in SP levels in HD frontal cortex, thalamus or hypothalamus.

Aged↗

Biological responses of the bovine teat to milking: information from measurements of milk flow-rate within single pulsation cycles.

The mass flow-rate (FR) of milk from the bovine teat within individual pulsation cycles was measured by continuous computation of the average optical density of the milk-air mixture within a teatcup. Measurements during milking were made on both live and excised teats using a range of teatcup liners, vacuum levels and pulsation characteristics. During a typical pulsation cycle, soon after the start of milking, milk FR from live teats reached a peak within 100 ms of the start of the flow period and fell to about 60% of the maximum value between 0.5 and 1.5 s of flow. If the liner was held open for longer than 1.5 s, the FR typically declined a further 10% over the next 10-15 s. After 10-15 s little or no further change occurred in milk FR at normal milking vacuum levels. Milk flow from excised teats reached a steady value within 100 ms of the start of the flow period and showed no subsequent fall in FR. Within individual pulsation cycles the changes in FR from live teats are affected by: (i) the degree of compressive load applied by the collapsed liner to the teat in the preceding cycle; and (ii) the duration of application of the compressive load. Increasing the degree of compressive load or the length of time of loading increases the peak milk FR of the next cycle by reducing the degree of congestion in the tissues of the teat surrounding the teat canal. Muscular effects are of secondary importance. The relatively small changes in milk FR associated with muscle contractions of the teat can bae seen most clearly at low milking vacuum levels (below about 30 kPa) or with an unsupported teat (e.ag. using a very distensible, thin-walled liner).

Animals↗

Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.

Gastrointestinal Hormones↗

Somatostatin, gastrointestinal peptides, and the carcinoid syndrome.

During a control infusion noradrenaline and alcohol each provoked carcinoid flushing in four of five patients and pentagastrin in two of five patients. When tetradecapeptide somatostatin was infused on another day no patient flushed at any time, even when 16 microgram of either noradrenaline or pentagastrin were administered. Carcinoid flushing was not associated with release of gastrin or any of the other vasoactive or postprandially released gut regulatory peptides measured. In a sixth patient with severe prolonged carcinoid flushing, subcutaneous Des AA1, 2, 4, 5, 12D Trp8 somatostatin markedly reduced the incidence and severity of flushing for two days. Somatostatin is thus a potent inhibitor of carcinoid flushing, but no evidence has been found for the gut hormones measured to be mediators of flushing.

Aged↗

The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.

The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.

Adult↗

Bombesin, somatostatin, and related peptides: actions on thermoregulation.

Bombesin acts within the anterior hypothalamic preoptic area to interfere with thermoregulation in the rat. The body temperature (Tb) of animals receiving bombesin varies in parallel with ambient temperature (Ta). Bombesin-induced reduction of Tb in animals at low Ta is associated with a marked reduction of oxygen consumption (VO2). Some somatostatin-related peptides, e.g., desAA 1,2,4,5,12,13 [D-Trp8]-somatostatin (ODT8-SS), act within the brain to prevent bombesin-induced reduction of VO2 and Tb. ODT8-SS also produces hyperthermia not associated with an increase in VO2.

Animals↗

Application of models for envelope growth to cell length distribution data for Pseudomonas aeruginosa at various specific growth rates.

Cell length distributions were determined for magnesium-limited steady-state populations of Pseudomonas aeruginosa grown in a chemostat at a variety of specific growth rates (0.037-0.621 h-1). The data were subjected to numerical analysis using an iterative procedure based upon the Collins and Richmond (1962) equation and various models for envelope growth. The cell length distributions of cultures growing at specific growth rates in excess of 0.276 h-1 could be modelled assuming constancy of the rate of increase in cell length, and the Zaritsky-Pritchard (1973) step growth model. Cultures growing at microns less than 0.276 h-1 had length distributions which skewed markedly towards the shorter length cells, and were not consistent with either linear, exponential nor step growth models. Pierucci (1978), however, proposed a model of linear envelope growth, which for slowly growing cultures predicted periods without envelope synthesis at the beginning of each division cycle. Application of such a model for slowly growing cultures produced similar skews in the cell length distributions, but could only adequately model the data when the periods of no-growth occurred in mid-cycle.

Models, Biological↗

Fluoroscopic radiation measurement in Saskatchewan.

A mail-out thermoluminescent dosimeter (TLD) system has been used to measure fluoroscopic surface dose rates very 8 weeks in Saskatchewan hospitals since 1976. Incentive for the program came from Saskatchewan radiologists. The mean of the annual dose rates for all units was 30.8 mGy/min (3.08 rads/min). Each year, 30% of the machines varied in output by 100% or more, 8% by 200% or more, and one machine's output increased by 800%. These measurements have allowed prompt correction of excessive dose levels or replacement of offending machines when the dose rate could be lowered sufficiently. No significant difference in surface dose rates between manually controlled units and units with automatic brightness control was found.

Fluoroscopy↗

Somatostatin analog: plasma catecholamine suppression mediated by the central nervous system.

The somatostatin analog, des-AA1,2,4,5,12,13-[D-Trp8]somatostatin (ODT8-SS), acts within the central nervous system to suppress the rise in plasma catecholamines associated with a variety of neural stimuli. Insulin-induced hypoglycemia or stress caused significant elevations in plasma catecholamines that were abolished by intracerebroventricular (icv) administration of ODT8-SS. Bombesin, carbachol, or 2-deoxyglucose, injected icv, evoked marked elevations in plasma epinephrine and norepineprine. These effects were also prevented by ODT8-SS given icv. In all experiments, ODT8-SS appeared to be more effective in lowering plasma epinephrine than in lowering plasma norepinephrine. Systemic administration of ODT8-SS was ineffective in lowering plasma catecholamine levels. Native somatostatin given icv produced inconsistent effects on plasma catecholamine levels. These data suggest that the somatostatin analog, ODT8-SS, acts within the central nervous system to modulate sympathetic nervous system activity. It is suggested, but not established, that this analog acts through the same receptor as native somatostatin.

Acoustic Stimulation↗