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S Dryden

Publications and source records attributed to S Dryden.

30 records · Page 2Linked to original sources
PubMed1995

Effect of sustained physiological hyperinsulinaemia on hypothalamic neuropeptide Y and NPY mRNA levels in the rat.

Neuropeptide Y (NPY) synthesized in the arcuato-paraventricular projection in the rat hypothalamus is thought to play an important role in controlling energy homeostasis. The factors that regulate hypothalamic NPY are not known but, amongst others, insulin has been postulated as an inhibitory modulatory agent. To test this hypothesis, normal male rats were given either insulin (2 units/day) or saline via subcutaneous osmotic minipumps for 3 days. Euglycaemia was maintained by a concomitant glucose infusion in insulin-infused rats which had peripheral insulin levels 5-8 times higher than saline-infused controls. Hyperinsulinaemic rats ate 42% less than controls, but their total energy intake (food intake plus glucose infusion) was higher than that of controls, and they gained more weight than controls during the experimental period. Hyperinsulinaemia had no significant effect on hypothalamic NPY mRNA or NPY levels in the arcuate nucleus. NPY concentrations in the paraventricular nucleus were, however, significantly increased by 73% in hyperinsulinaemic rats, but were closely similar to controls in all other areas. Insulin may act as a satiety factor in that hyperinsulinaemic rats ate less, but the fact that these animals had increased total energy intake and gained excessive weight suggests that insulin may not function as an overall regulator of energy balance. In addition, physiological hyperinsulinaemia does not apparently inhibit NPY gene expression in the arcuate nucleus. Due to the lack of effect of hyperinsulinaemia on NPY synthesis in the arcuate nucleus, the elevated NPY concentrations in the paraventricular nucleus could result from a reduction of its release, which would be in keeping with the reduction in food intake.

Analysis of Variance↗
PubMed1995

Interleukin-1 beta-induced anorexia and pyrexia in rat: relationship to hypothalamic neuropeptide Y.

We investigated the effect of recombinant human interleukin-1 beta (rhIL-1 beta)-induced anorexia and pyrexia on the hypothalamic neuropeptide Y (NPY)-ergic system, which stimulates feeding and reduces thermogenesis. In meal-fed rats, food intake decreased by 83%, 90 min after IL-1 beta treatment (1.3 micrograms/100 g ip; n - 8) vs. controls. NPY concentrations were significantly higher in the medial preoptic area (MPO), paraventricular (PVN), ventromedial (VMN), and dorsomedial (DMN) nuclei but unchanged in the arcuate nucleus (ARC) in both IL-1 beta-treated and pair-fed groups. Indomethacin (0.25 mg/100 g ip) reduced IL-1 beta-induced anorexia and tended to normalize NPY concentrations. In study 2, IL-1 beta increased core temperature by 1.1 degrees C above preinjection values (P < 0.001) and significantly raised NPY concentrations in the MPO, PVN, VMN, and DMN compared with controls, 60 min postinjection. Indomethacin prevented the pyrexia and normalized hypothalamic NPY levels. As NPY concentrations were not increased in the ARC (the hypothalamic site of synthesis), we suggest that the increased NPY levels may result from blocked release, which would be in accord with the known experimental effects of NPY.

Animals↗
PubMed1994

Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations.

Megestrol acetate, a synthetic progestogen, stimulates appetite through an unknown mechanism. We tested the hypothesis that it might act, at least in part, by stimulating the activity of hypothalamic pathways containing neuropeptide Y, a potent central appetite stimulant in rats. Administration of megestrol acetate (50 mg/kg/day, n = 8) for 9 days significantly increased food and water intake compared with untreated controls (n = 8). Treated rats showed significant (90-140%) increases in neuropeptide Y concentrations in the arcuate nucleus (where neuropeptide Y is synthesized), in the lateral hypothalamic area (through which arcuate neurones project) and in the medial preoptic area, ventromedial nucleus and dorsomedial nucleus. The latter are sites of neuropeptide Y release and sensitive to neuropeptide Y-induced hyperphagia. Megestrol acetate may therefore stimulate neuropeptide Y synthesis, transport and release, and this could contribute to its appetite-stimulating effects.

Analysis of Variance↗
PubMed1994

Acute dexfenfluramine administration normalizes glucose tolerance in rats with insulin-deficient diabetes.

Dexfenfluramine has been shown to lower blood glucose concentrations independently of its effects in reducing food intake and body weight, in human and animal syndromes of non-insulin dependent diabetes. This study aimed to determine whether dexfenfluramine could also reduce glycaemia in rats with severe insulin-deficient diabetes induced by the beta-cell toxin, streptozotocin (55 mg kg-1). Three weeks after diabetes induction, nine groups (each n = 10) of diabetic and non-diabetic rats underwent oral glucose tolerance tests (1 g kg-1, by gavage). These tests were preceded by 12-18 h of fasting to remove the confounding effects of hyperphagia in diabetic rats, and to stabilize glycaemia. Dexfenfluramine (1.0 mg kg-1), given 2 h before the glucose challenge, significantly reduced basal glycaemia and decreased the post-challenge glycaemic rise (P < 0.01 vs. untreated diabetics). Dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 both further flattened the post-challenge glycaemic profiles (both P < 0.01 vs. untreated diabetics) and achieved levels that did not differ significantly from those in non-diabetics (both P > 0.05). Subsequently, the studies using dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 were repeated to determine whether the drug affected plasma insulin levels 2 h after dosing. In diabetic rats, plasma insulin concentrations were reduced to 10-20% of non-diabetic values, and were not significantly altered by dexfenfluramine. Acute dexfenfluramine administration therefore improves and (at dosages of 2.5 and 5.0 mg kg-1) essentially normalizes glucose tolerance in rats with severe insulin-deficient diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Obesity is a vast and ever-expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well-known associations with non-insulin-dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6-8% of total health-care expenditure in North America [1] (similar estimates probably apply to Western Europe). Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach. This article argues that new anti-obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.

Animals↗
PubMed1994

Effects of chronic vanadate administration in the STZ-induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding.

Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Taking the 'institution' out of hospital care. Inpatient accommodation for oncology patients.

1. Inpatient accommodation was provided for oncology patients receiving radiotherapy treatment to give them more freedom and independence. 2. A holistic approach was adopted whereby the effects of cancer on the individual were evaluated and catered for. 3. The philosophy at Raeburn House aims to promote independence of each individual throughout the treatment process in preparation for their discharge.

Emotions↗
PubMed1989

Asthma therapy and a tracheostomy.

A spacer device was modified to deliver aerosols of beclomethasone diproprionate, ipratropium and bromide salbutamol, to an asthmatic child with a tracheostomy, where symptoms were poorly controlled with nebulized therapy. This resulted in a marked improvement in symptoms and a dramatic reduction in the time spent administering drugs.

Aerosols↗
PubMedDate not supplied

Neuropeptide Y receptor numbers are reduced in the hypothalamus of streptozotocin-diabetic and food-deprived rats: further evidence of increased activity of hypothalamic NPY-containing pathways.

Neuropeptide Y (NPY) injected into the hypothalamus stimulates feeding and affects pituitary secretion. Insulin-deficient diabetes and food deprivation markedly increase hypothalamic NPY and NPY mRNA levels, suggesting increased activity of NPYergic pathways in the hypothalamus, which could account for hyperphagia and neuroendocrine changes in these conditions. To clarify these changes, NPY receptor characteristics were compared amongst rats with 3-weeks' untreated streptozotocin diabetes, insulin-treated normoglycemic diabetics, and non-diabetics, and also in food-deprived (72 h), food-deprived then refed, and in freely fed rats. Hypothalamic tissue homogenates (pooled from 3 rats; n = 9 per group) in Tris/HCl buffer were incubated with 30 pM [125I]porcine NPY and unlabeled NPY (range, 1 pM to 1 microM) for 1 h. Bound and free fractions were separated by vacuum filtration. Scatchard analysis revealed both high-affinity (Kd 0.3-0.8 nM) and low-affinity (Kd 14-40 nM) NPY receptor populations. Compared with nondiabetics, diabetic rats showed significantly reduced numbers (Bmax) of both high-affinity receptors (10 +/- 2 vs. 57 +/- 2 pmol/mg protein; p < 0.001) and low-affinity receptors (113 +/- 25 vs. 544 +/- 48 pmol/mg protein; p < 0.001). Insulin treatment partially restored Bmax of both high- and low-affinity receptors (24 +/- 1 and 334 +/- 60 pmol/mg protein, respectively; p < 0.01 vs. both other groups). Food deprivation also reduced Bmax of high-affinity (36 +/- 2 vs. 56 +/- 7 pmol/mg protein in freely fed; p < 0.05) and low-affinity receptors (288 +/- 6 vs. 457 +/- 17 pmol/mg protein; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Increased neuropeptide Y concentrations in specific hypothalamic nuclei of the rat following treatment with methysergide: evidence that NPY may mediate serotonin's effects on food intake.

Neuropeptide Y (NPY) is a potent central appetite stimulant found in hypothalamic neurons that have close anatomical associations with neurons containing serotonin, a powerful anorectic agent. To determine whether the two neurotransmitters interact functionally, we have studied the effects on regional hypothalamic NPY concentrations of acute and chronic administration of methysergide, a 5-HT1BC/serotonin receptor antagonist. Chronic methysergide treatment (10 mg/kg/day) was given by subcutaneously implanted osmotic minipumps (n = 8). Acute effects of methysergide were determined 4 h after a single injection (10 mg/kg) in a separate group (n = 8). Controls (n = 8) had implanted minipumps delivering saline, and also received a saline injection 4 h before sacrifice. Food intake was significantly increased (p < 0.01) by both acute and chronic methysergide treatment. In the chronically treated rats, NPY levels were significantly increased over controls in the arcuate nucleus (ARC; by 41%, p = 0.02) and paraventricular nucleus (PVN; by 40%, p < 0.01). Acute methysergide treatment also increased NPY concentrations in the ARC (by 81%, p < 0.01) and PVN (by 30%, p < 0.01). Methysergide administration, which stimulated feeding, therefore raised NPY concentrations in the ARC, where NPY is synthesized, and in the PVN, a major site of NPY release where NPY injection induces hyperphagia. These findings suggest that NPYergic and serotoninergic innervations in the hypothalamus interact to regulate food intake, and raise the possibility that increased NPY release may mediate the hyperphagic effect of serotoninergic 5-HT1BC/receptor blockade.

Animals↗