A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.
The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4-6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P<0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P<0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted. (+info)
Effect of postweaning feeding on the performance and energy balance of female rabbits at different physiological states.
The feeding of a high-fiber and low-energy diet to young rabbit does from weaning to the first kindling was used to modify their body reserves, stimulate their energy intake, and reduce the energy deficit during the first lactation. Rabbits (53 per group) were given ad libitum access to either a control or high-fiber diet (CP, 17.6 vs 15.8% of DM; crude fiber, 15.5 vs 19.9% of DM; digestible energy, 2,565 vs 2,261 kcal/kg of DM, respectively) from weaning to their first kindling. During lactation, both groups received the same diet, which contained 19.3% CP, 16.5% crude fiber, and 2,634 kcal/kg digestible energy (dry matter basis). Four comparative slaughters were performed to estimate the chemical and energy balance of rabbit does at different physiological states: at the beginning of the trial (12 rabbits, 45 d of age), at mating (10 rabbits per group, 136 d), at kindling (10 rabbits per group, 167 d), and at the end of lactation (12 and 11 rabbits for the control and the high-fiber group, 197 d). Large changes in body weight and composition were observed between slaughters. From 45 d to mating, doe body fat and energy increased 7.93 and 4.64 times the initial content, respectively. During pregnancy, body protein concentration decreased from 203 to 186 g/kg. At the end of lactation, body fat and energy concentration were reduced to values close to those measured at 45 d of age. Dietary treatment affected body chemical and energy balance during pregnancy and lactation but not reproductive and lactational performance. The high-fiber diet stimulated feed intake from weaning to the first kindling but not dietary energy intake. During lactation, the rabbits fed the high-fiber diet ate 10 kcal x d(-1) x kg live weight(-.75) more and lost less body fat (-405 vs -504 g) and body energy (-3,628 vs -4,294 kcal) than the does fed the control diet (P < .001). In the same period, all does showed water and protein retention (185 and 45 g, on average) regardless of dietary treatment. In conclusion, feeding young does a high-fiber diet until their first kindling reduced the chemical and energy body deficit at the end of the first lactation. (+info)
Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility.
BACKGROUND: Aging is associated with a decrease in appetite and a slowing of gastric emptying. The gastrointestinal hormones cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) may mediate these changes. OBJECTIVE: We investigated whether aging influenced the secretion of CCK, GLP-1, and PYY and their effects on appetite and pyloric motility. DESIGN: Eight healthy older (65-80 y) and 7 younger (20-34 y) men received isoenergetic (12.1 kJ/min) intraduodenal infusions of lipid and glucose for 120 min on separate days. Plasma CCK, GLP-1, and PYY concentrations were measured. RESULTS: Plasma CCK concentrations were higher in older than in younger subjects (P = 0.004) as a result of higher baseline values (4.7+/-0.2 compared with 3.2+/-0.2 pmol/L; P < 0.0001) and a greater rise during lipid infusion (increase from baseline: 7.1+/-0.5 compared with 5.3+/-0.6 pmol/L; P = 0.048). Plasma GLP-1 and PYY concentrations were not significantly different between groups. The decrease in hunger during intraduodenal lipid infusion was inversely related to the increase in CCK, GLP-1, and PYY in younger but not older subjects. During intraduodenal lipid infusion, the increase in isolated pyloric pressure wave (IPPW) frequency was positively related to GLP-1 and PYY and the increase in IPPW amplitude was positively related to CCK in older but not younger subjects, whereas the increase in IPPW amplitude and pyloric tone was negatively related to GLP-1 and PYY in younger subjects. CONCLUSIONS: Human aging is associated with increased CCK concentrations, which may contribute to the slowing of gastric emptying, mediated by increased pyloric motility. The role of increased plasma CCK concentrations in mediating the age-related decrease in appetite remains to be established. (+info)
Sodium depletion and aldosterone decrease dopamine transporter activity in nucleus accumbens but not striatum.
Motivated behaviors, including sodium (Na) appetite, are correlated with increased dopamine (DA) transmission in the nucleus accumbens (NAc). DA transporter (DAT) modulation affects DA transmission and may play a role in motivated behaviors. In vivo Na depletion, which reliably induces Na appetite, was correlated with robust decreases in DA uptake via the DAT in the rat NAc with rotating disk electrode voltammetry [1,277 +/- 162 vs. 575 +/- 89 pmol. s-1. g-1; Vmax of transport for control vs. Na-depleted tissue]. Plasma aldosterone (Aldo) levels increase after in vivo Na depletion and contribute to Na appetite. Decreased DAT activity in the NAc was observed after in vitro Aldo treatment (428 +/- 28 vs. 300 +/- 25 pmol. s-1. g-1). Neither treatment affected DAT activity in the striatum. These results suggest that a direct action of Aldo is one possible mechanism by which Na depletion induces a reduction in DAT activity in the NAc. Reduced DAT activity may play a role in generating increased NAc DA transmission during Na appetite, which may underlie the motivating properties of Na for the Na-depleted rat. (+info)
Roles of aldosterone and angiotensin in maturation of sodium appetite in furosemide-treated rats.
When rats are treated with furosemide, there is a rapid natriuresis. However, increased sodium appetite does not occur until some time later. One hypothesis to explain this delay is that increased circulating levels of the hormones of sodium depletion prime or sensitize the brain circuits involved in sodium appetite, perhaps by induction of target gene(s). In the present study, we describe the time course of the temporal maturation of sodium appetite after furosemide treatment and the associated changes in plasma levels of ANG II and aldosterone and in plasma volume. Sodium appetite is modest 3 h after furosemide treatment, is increased after 12 h, and is still larger after 24 h. This pattern is evident with repeated testing. Plasma levels of aldosterone and plasma renin activity are substantially increased 3 h after furosemide treatment, and so the NaCl appetite cannot result simply from progressively increasing levels of these hormones. Furthermore, activation of the subfornical organ and the ventral lamina terminalis, assessed with c-Fos immunocytochemistry, did not differ across these three times. Metyrapone, an inhibitor of adrenal steroid synthesis, was used to examine sodium appetite in the absence of elevations in aldosterone after furosemide treatment. Although metyrapone effectively blocked the increase in aldosterone, it was without effect on the appetite 3 or 24 h after furosemide treatment. Furthermore, elevations of plasma aldosterone by the use of minipumps for several days before furosemide treatment did not prime or potentiate but instead tended to inhibit the induced sodium appetite, despite achieving levels of aldosterone and plasma renin activity typically associated with a robust sodium appetite. Infusions of DOCA gave a similar result. Lastly, minipump infusions of ANG II also did not potentiate sodium appetite. Thus neither addition nor subtraction of these hormones alone influenced sodium appetite under these conditions. (+info)
Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2.
Glucagon-like peptide-1-(7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis. Recent experimental evidence in animals and healthy subjects suggests that GLP-1 has a role in controlling appetite and energy intake in humans. We have therefore examined in a double-blind, placebo-controlled, crossover study in 12 patients with diabetes type 2 the effect of intravenously infused GLP-1 on appetite sensations and energy intake. On 2 days, either saline or GLP-1 (1.5 pmol. kg-1. min-1) was given throughout the experiment. Visual analog scales were used to assess appetite sensations; furthermore, food and fluid intake of a test meal were recorded, and blood was sampled for analysis of plasma glucose and hormone levels. GLP-1 infusion enhanced satiety and fullness compared with placebo (P = 0.028 for fullness and P = 0.026 for hunger feelings). Energy intake was reduced by 27% by GLP-1 (P = 0.034) compared with saline. The results demonstrate a marked effect of GLP-1 on appetite by showing enhanced satiety and reduced energy intake in patients with diabetes type 2. (+info)
Neuropeptide Y restores appetite and alters concentrations of GH after central administration to endotoxic sheep.
The objective of this study was to determine whether neuropeptide Y (NPY) and recombinant human interleukin-1 receptor antagonist (IL-1ra) would: first, increase food intake; secondly, decrease concentrations of GH; thirdly, reduce GHRH-induced release of GH; and fourthly, reduce changes to concentrations of IGF-I in plasma during experimental endotoxemia in sheep. Six treatments were given to six castrated male sheep in a 6x6 Latin square treatment order. Osmotic mini-pumps were implanted at 0 h and a jugular vein was cannulated. Each sheep was continuously infused with saline (0.9%) or lipopolysaccharide (LPS) (20 micrograms/kg per 24 h, s.c.) at 10 microliters/h for 72 h via the osmotic mini-pumps. Blood samples (3 ml) were collected at 15-min intervals from 24 to 33 h. At 26 h, one of three treatments (artificial cerebrospinal fluid, NPY or IL-1ra) was injected i.c.v. within 30 s (0.3 microgram/kg), then infused i.c.v. from 26 to 33 h (600 microliters/h) at 0.3 microgram/kg per h. GHRH was injected i.v. (0.075 microgram/kg) at 32 h after which blood samples were collected at 5, 10, 15, 30, 45 and 60 min. Feed intake was reduced up to 50% for 48 h in LPS-treated compared with non-LPS-treated sheep. NPY restored feed intake in LPS-treated sheep and induced hyperphagia in non-LPS-treated sheep from 24 to 48 h. In contrast, IL-1ra did not affect appetite. Injection of NPY increased concentrations of GH from 26 to 27 h, while IL-1ra had no effect. Infusion of NPY suppressed GHRH-induced release of GH. However, no treatment altered pulse secretion parameters of GH. Concentrations of IGF-I were 20% higher at 72 h in LPS-treated sheep given NPY than in sheep treated with LPS alone, and this may reflect increased appetite from 24 to 48 h. We concluded that reduced appetite during endotoxemia is due to down-regulation of an NPY-mediated mechanism. Furthermore, NPY stimulates release of GH in healthy sheep, does not reduce pulse secretion parameters of GH, but does suppress GHRH-induced release of GH in endotoxic sheep. Therefore, NPY may be an important neurotransmitter linking appetite with regulation of GH during endotoxemic and healthy states in sheep. (+info)
Influences of long-term administration of 24R, 25-dihydroxyvitamin D3, a vitamin D3 derivative, in rats.
In order to examine the influences by long-term feeding of 24R, 25 dihydroxyvitamin D3[24R, 25(OH)2D3], an active form of vitamin D, Wistar rats (14-week-old, male, 20 rats/group) were fed a powder diet containing 0 or 5 ppm 24R, 25(OH)2D3 for 57 weeks. Final body weights and total food consumption were comparable between the groups. Urinary calcium levels were significantly (p < 0.05 or 0.01) increased by the administration of 24R, 25(OH)2D3 at weeks 3, 22 and 56, although the levels of serum calcium did not differ between the groups at the termination of week 57. In the 24R, 25(OH)2D3 group, weights of the adrenals and femurs were significantly (p < 0.01) increased. Histopathologically, this was found due to thickening of cortical bone in the femurs, and medullary hyperplasia and pheochromocytoma of the adrenals. Immunohistochemically, proliferating cell nuclear antigen (PCNA)-labeling indices for intact adrenal medulla, medullary hyperplasia and pheochromocytoma in the 24R, 25(OH)2D3 group were respectively 1.82 +/- 1.21, 5.88 +/- 4.13 and 16, all higher than that for the adrenal medulla in the control group (0.87 +/- 0.67). These results indicate that 24R, 25(OH)2D3 at a dose with which serum calcium is not chronically increased causes thickening of the cortex of the femur, and development of adrenal proliferative lesions, suggesting that rats may be too sensitive for results to be relevant to human risk assessment. (+info)