Re: Localized hyperthermia versus the sham procedure in obstructive benign hyperplasia of the prostate: a prospective randomized study.
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Humans↗
Biomedical subjects
A H Meier
Publications and source records attributed to A H Meier.
Daily rhythm of plasma insulin in Japanese quail (Coturnix c. japonica) fed ad libitum.
1. Plasma levels of immuno-reactive insulin (IRI) of 6 groups of 5-week-old quail, held on a 16L:8D photoregime, were measured every 4 hr, for 24 hr. 2. Concentrations of plasma IRI varied during the 24 hr period (Anova, P < 0.003). Insulin levels were high (mean = 857 pg/ml) from 6 a.m. (light onset) until 6 p.m. (4 hr before light offset) and low (mean = 185 pg/ml) at 10 p.m. and 2 a.m. 3. IRI concentrations at 6 a.m., 10 a.m., 2 p.m. and 6 p.m. were significantly different from values at 2 a.m. and 10 p.m. by Waller grouping. 4. Low IRI levels at light offset (10 p.m.--when the birds had full crops and were in an absorptive state) and high levels at light onset (6 a.m.--before feeding resumed) indicate that feeding does not fully account for the IRI rhythm.
Animals↗
Circadian neuroendocrine role in age-related changes in body fat stores and insulin sensitivity of the male Sprague-Dawley rat.
A role for circadian neuroendocrine rhythms in the age-related development of obesity and insulin resistance was investigated in the male Sprague-Dawley rat. The phases and amplitudes of the plasma rhythms of several metabolic hormones (i.e., corticosterone, prolactin, insulin, and triiodothyronine) differed in lean, insulin-sensitive (3-week-old rats), insulin-resistant (8-week-old rats) and obese, insulin-resistant (44-week-old rats) animals. Simulation of the daily rhythms of endogenous corticosterone and prolactin by daily injections of the hormones at times corresponding to the peak levels found in 3-week-old rats reversed age-related increases in insulin resistance and body fat in older (5-6-month-old) rats. Ten such daily injections of corticosterone and prolactin in 12-14-week-old rats produced long-term reductions in body fat stores (30%), plasma insulin concentration (40%), and insulin resistance (60%) (determined by a glucose tolerance test) measured 11-14 weeks after the treatment. Alterations in circadian neuroendocrine rhythms may account for age-related changes in carbohydrate and lipid metabolism in the male Sprague-Dawley rat, and resetting of these rhythms by appropriately timed daily injections of corticosterone and prolactin may help maintain metabolism characteristic of younger animals.
Adipose Tissue↗
Effects of pulsatile glucose stimuli on long-term insulin secretory patterns in islets of Langerhans microdissected from Syrian hamsters.
The long-term effects of continuous and pulsatile glucose stimulation of islets of Langerhans microdissected from Syrian hamsters were examined. In the presence of a continuous glucose stimulus insulin secretion peaked during the first 3 h of stimulation followed by a decrease. In the presence of 11.2 mM glucose a second smaller peak of insulin secretion was observed 14-16 h after the perifusion started. Irrespective of the glucose concentration, insulin secretion then steadily decreased and reached very low levels by the end of the 48-h perifusion. However, glucose stimulus provided in a pulsatile manner appeared to reduce this rate of decrease in insulin secretion. Thus, after 48 h, islets exposed to the pulsatile glucose stimulus showed greater insulin responsiveness to glucose than those exposed to a constant glucose stimulus.
Animals↗
Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters.
Bromocriptine redirects metabolism and prevents seasonal onset of the obese hyperinsulinemic state in Syrian hamsters. Metabolic and hormonal effects of bromocriptine were studied in seasonally obese female Syrian hamsters, Mesocricetus auratus. Daily injections of bromocriptine and vehicle (controls) were made at light onset (10:14-h light-dark cycle) for 10 wk. After 9 wk of treatment blood samples were taken every 4 h during a day for assays of hormones, glucose, triglyceride, and fatty acids, and after 10 wk of treatment, tests were carried out to measure insulin-stimulated glucose disposal during a hyperinsulinemic clamp, lipid mobilization (rate of glycerol appearance), protein turnover (lysine flux and deamination), and body composition (deuterium dilution). Bromocriptine reduced percent body fat by 53% and increased percent lean body mass by 8%. It also decreased triglyceride levels by 52% and plasma free fatty acid concentration during the dark-near light onset by 49% and glycerol appearance by 25%. Protein synthesis and catabolism were increased by 62 and 56%, respectively, and deamination of amino acid was decreased by 53% by bromocriptine. Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Alterations in body fat stores and plasma insulin levels with daily intervals of heat exposure in Holtzman rats.
The ability of timed daily increases in ambient temperature (from 22 +/- 1 degree C to 40 +/- 1 degree C for 2 h) to alter body fat stores, blood lipid levels, and insulin resistance were tested in male Holtzman rats. Of the six times of day tested only temperature pulses administered 16 h after light onset consistently decreased body weights, retroperitoneal fat stores, and plasma insulin levels. Subsequently, temperature pulses were administered either 0 (TP0) or 16 (TP16) h after light onset (light-dark 12:12 h). While no differences were observed between the TP0 group and the constant temperature (22 degrees C) controls, decreases in body weight gain, food consumption, retroperitoneal fat stores, and plasma concentrations of insulin, cholesterol, and triglycerides were consistently observed in the TP16 group. Although changes in plasma glucose during an oral glucose tolerance test were similar when the two treatment groups were compared with their respective controls, glucose tolerance was achieved with less insulin in the TP16 animals than in their respective controls. Insulin effectiveness was greater in the TP16 group as indicated by a decrease in plasma glucose, after insulin injection, that was of greater magnitude and longer duration than in controls. Hence, timed daily increases in ambient temperature may decrease obesity in part by decreasing plasma insulin levels apparently as a consequence of increased tissue sensitivity to insulin (greater glucose tolerance and less insulin intolerance). Because the treatment is effective only at a particular time of day the findings support a role for circadian neuroendocrine interactions in the regulation of these metabolic states.
Acclimatization↗
Daily intervals of heat exposure alter the phase of the daily variation of plasma hormones in Holtzman rats.
The effects of timed daily increases in ambient temperature (thermopulses) (from 22 +/- 1 to 40 +/- 1 degree C for 2 h) on daily variations of hormones involved in glucose and lipid metabolism were tested in male Holtzman rats (3-4 mo old) exposed to a 12-h daily photoperiod. The thermopulses were administered for 14 days either at light onset (TP0) or 16 h after light onset (TP16). Body weights and food consumption were monitored during the experiment. Retroperitoneal fat weights and plasma concentrations of insulin, glucose, glucagon, corticosterone, and prolactin were determined from blood taken every 4 h during a 24-h period commencing 24 h after the last thermopulse. TP0 treatment did not alter any of the parameters tested. Conversely, TP16 treatment obliterated the daily rhythms of insulin and corticosterone present in the controls (nonthermopulsed) and decreased body weight gains, retroperitoneal fat stores, food consumption, and the baseline levels of plasma insulin and corticosterone. The present study supports a role for circadian neuroendocrine rhythms in the reduction of fat stores induced by properly timed daily thermopulses.
Acclimatization↗
Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics.
Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight. Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4-8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.
Body Composition↗
Transurethral radiofrequency heating or thermotherapy for benign prostatic hypertrophy: a prospective trial on 65 consecutive cases.
65 consecutive cases with symptomatic benign prostate hypertrophy were treated with transurethral radiowave thermotherapy (TURF) using the Thermex-II at a temperature of 44.5 degrees C. We report uroflowmetry and symptom scores after a follow-up of 6 months. The mean age was 63 years, the mean maximal flow (Qmax) was 8.3 ml/s, mean voided volume was 195.6 ml, mean residual urine was 60.7 ml and the mean Madsen symptom score 9.7. Values at baseline and at 1, 3 and 6 months after TURF are discussed. The mean subjective symptom score dropped to 6.3 (p < 0.01). In the entire group, the objective measure scores (OMS) did not change significantly. However the OMS improved significantly in a subgroup with a Qmax < 10.0 ml/s. The Madsen symptom score improved in 70% of the cases after 6 months.
Aged↗
Bromocriptine inhibits the seasonally occurring obesity, hyperinsulinemia, insulin resistance, and impaired glucose tolerance in the Syrian hamster, Mesocricetus auratus.
Seasonally obese-hyperinsulinemic female Syrian hamsters were injected daily with bromocriptine or saline for a period of 34 days to test for effects of bromocriptine on body fat store levels, hepatic triglyceride secretion, glucose tolerance, and plasma insulin and glucose concentrations. The effects of bromocriptine on body fat store levels, as well as on plasma insulin and glucose concentrations, in seasonally obese hamsters were compared with the levels of body fat, plasma insulin, and plasma glucose observed in seasonally lean hamsters. Bromocriptine treatment substantially improved glucose intolerance and reduced the total and stimulated areas under the glucose tolerance curve by 33% after 14 days of treatment. After 34 days of treatment, bromocriptine reduced body fat store levels by 36% and hepatic triglyceride secretion by 40% without any concurrent change in food consumption. Furthermore, bromocriptine reduced the plasma insulin level by 70%, while slightly reducing plasma glucose concentration (ie, 68% reduction in the insulin to glucose ratio). The reductions of body fat, plasma insulin, and plasma insulin to glucose ratio produced by bromocriptine in seasonally obese hamsters are equivalent to those observed in seasonally lean hamsters. Shifts in phase relationships of circadian neuroendocrine rhythms have been demonstrated to regulate annual cycles of metabolism in vertebrates, including the Syrian hamster. The effects of bromocriptine can also be explained as an alteration of such a circadian mechanism.
Adipose Tissue↗
Effect of 12 hr temporal relation of serotonin and dopamine precursor drugs (5-HTP and L-DOPA) on photosexual responses of immature Japanese quail.
To study the interaction of photoperiod and circadian neurotransmitter activity, L-DOPA L-dihydroxyphenylalanine, dopamine precursor) was administered daily, 12 hr after 5-HTP (5-hydroxy tryptophan, serotonin precursor) in sexually immature Japanese quail, raised under short photoperiod (LD8:16) since hatching. The 12 hr treatment of 5-HTP and L-DOPA was given under continuous condition of light for 11 days. After treatment the quail were transferred to intermediate day length (LD 13.5:10.5). The cloacal gland size of drug treated group increased significantly in comparison to control. The quail were then transferred to short photoperiod (LD 8:16). The cloacal gland size of both the groups started decreasing gradually but the rate was significantly low in drug treated quail in comparison to control. The results indicate that the endogenous mechanism controlling seasonality may be reset by drugs that influence serotonergic and dopaminergic activity. The 12 hr relation between the two drugs is stimulatory for gonadal growth under intermediate day length and retards the rate of regression when transferred to short days.
5-Hydroxytryptophan↗
Hepatic vagotomy abolishes the circadian rhythm of lipogenic responsiveness to insulin and reduces fat stores in hamsters.
The effects of hepatic vagotomy upon the circadian rhythm of lipogenesis and body fat store levels were tested in seasonally obese Syrian hamsters. Lipogenesis was studied 8 weeks after surgery by measuring the incorporation of label into epididymal and retroperitoneal fat pad lipid in animals killed 30 min after intraperitoneal [3H]-glucose injection and 2 h after bovine insulin injections. A marked circadian variation in insulin-stimulated lipogenesis was present in sham-operated controls. The peak of lipogenic activity occurred at light onset and was 3-fold greater than during the middle of the photophase. The peak in the circadian variation of plasma insulin coincided with the peak of lipogenic responsiveness to insulin in these animals. Hepatic vagotomy completely abolished the circadian variation in insulin-stimulated lipogenesis and reduced the magnitude of the daily lipogenic peak at light onset by 65%, but only slightly altered the phase of the circadian variation in plasma insulin by 4 h. Hepatic vagotomy did not influence plasma glucose levels, which did not vary as a function of time of day in either group. Body fat stores were severely reduced (40%) by hepatic vagotomy when examined 8 weeks after surgery. The present study demonstrates important roles for interactions of the circadian rhythms of insulin and tissue lipogenic responses to insulin in the regulation of body fat stores. Furthermore, this study demonstrates that hepatic vagal activity regulates the daily interval of lipogenic responsiveness to insulin and thereby directly influences body fat stores in the Syrian hamster.
Adipose Tissue↗
Bromocriptine-induced reduction of body fat in pigs.
An experiment was conducted with 36 crossbred finishing pigs (18 male castrates and 18 females) to evaluate the effect of bromocriptine implants on growth, feed intake, feed efficiency, plasma urea nitrogen (PUN) and carcass characteristics. Three levels of bromocriptine (0, 5 and 10 mg/[pig.d]) were administered, via implants at the base of the ear, to six (two replicates of three) male castrates or to six (two replicates of three) intact female pigs (2 x 3 factorial arrangement of treatments). Average initial weight of pigs at the time of implantation was 89.7 kg, and the implants remained in the pigs for 28 (replicate 1) or 30 (replicate 2) d prior to slaughter. Gain, feed intake and efficiency of feed utilization were not affected (P greater than .10) by bromocriptine. Plasma urea nitrogen was lower in female pigs administered 10 mg bromocriptine; bromocriptine did not affect PUN of male pigs (gender x bromocriptine, P less than .08). Tenth rib fat thickness and average backfat thickness were lower (P less than .06) and percentage of muscling was higher (P less than .06) in pigs implanted with bromocriptine. Female pigs had less 10th rib fat but larger loin eye areas and a greater percentage of muscling than male pigs.
Adipose Tissue↗
Reductions of body fat stores and total plasma cholesterol and triglyceride concentrations in several species by bromocriptine treatment.
Administrations (injections and in feed) of bromocriptine, a dopamine agonist that inhibits prolactin secretion, reduced body fat stores and plasma total cholesterol and triglyceride concentrations in several rodent species (Syrian hamsters, Djungarian hamsters, Swiss Webster mice and obese Zucker rats). Body fat indices were reduced by at least 50% in the hamsters and mice within 10-15 days of treatment and by 29% in 8 weeks in the rats. Bromocriptine reduced total plasma cholesterol concentration by 17% in Syrian hamsters, 41% in mice and 30% in rats fasted before blood sampling. In nonfasted obese rats, bromocriptine dramatically reduced both cholesterol (from 440 to 130 mg/dl) and triglyceride (from 1570 to 540 mg/dl) levels compared with controls. These findings offer further evidence for a primary role of prolactin in lipid metabolism and indicate that bromocriptine may be useful for treating obesity and lipid-based cardiovascular disorders.
Adipose Tissue↗
Prolactin influences the circadian rhythm of lipogenesis in primary cultured hepatocytes.
Hepatocytes from male Syrian hamsters were cultured in the presence of insulin and assayed for lipogenesis by following (14C)acetate incorporation into total cell lipid at 4 hourly intervals over a 48-h period. Circadian rhythms of lipogenic activity were observed on days 2 and 3 of culture. Although the phases of the rhythms were similar, the amplitude of the peak levels of lipogenesis declined from day 2 to 3. Addition of prolactin to the culture reversed this decline when introduced at specific times relative to the lipogenic peaks. Prolactin more than doubled lipogenesis only at the daily peaks of lipogenic activity and only when added to culture 20 h before the times of peak lipogenesis. The results are the first to demonstrate important roles for circadian rhythms and a direct prolactin stimulation in the regulation of lipogenesis in primary hepatocyte culture.
Animals↗
Melatonin mediates alternation of seasonality in Syrian hamsters.
The annual cycle of reproductive activity in the Syrian hamster, Mesocricetus auratus, is the result of interaction between seasonal changes in daylength (photoperiodism) and seasonal changes in responsiveness to daylength (seasonality). The present experiment was designed to investigate the role of the pineal gland and its hormone, melatonin, in the alternation of seasonality (scotosensitivity and scotorefractoriness). Male hamsters were maintained on short daylengths (10L:14D) to establish scotorefractoriness, and then they were transferred to long daylengths (14L:10D) for conversion to scotosensitivity (sensitive to short daylengths). Before transfer to long daylengths, some of the hamsters were pinealectomized and others were sham-operated or unoperated. Some of the pinealectomized hamsters received single daily melatonin or saline injections while on long daylengths. After 14 wk on long daylengths, the hamsters were transferred to short daylengths for 10 wk to test for conversion to scotosensitivity. Pinealectomized hamsters were given three daily melatonin injections while on short daylengths. Such treatment is known to promote gonadal regression in scotosensitive but not in scotorefractory hamsters. Examination of testes after the short daylength interval revealed that exposure of nonpinealectomized hamsters to long daylengths had reestablished scotosensitivity (regressed testes). Pinealectomized hamsters that received no melatonin replacement while on long daylengths remained scotorefractory (enlarged testes), whereas those that received single daily injections of melatonin during long daylengths were found to be scotosensitive. These results indicate that a daily pulse of melatonin during expsoure to long daylengths has an important role in reestablishing responsiveness (scotosensitivity) to short daylengths.
Animals↗
Bromocriptine alters hormone rhythms and lipid metabolism in swine.
Hormones, metabolites and activities involved in lipid synthesis were assayed in pigs made leaner by bromocriptine treatment. Market size female swine were allowed free access to food under natural lighting conditions and implanted with bromocriptine pellets designed to release 10 mg/pig/day for 28 days in an effort to inhibit prolactin secretion. Between the 2nd and 3rd week of treatment, plasma samples were obtained from each group at 4-hour intervals throughout the day for assays of prolactin, cortisol, insulin, triglyceride, cholesterol and glucose concentrations. Twenty-eight or thirty days after the implantations, all animals were sacrificed for determinations of backfat thickness and insulin binding in the liver. At sacrifice, bromocriptine treatment reduced backfat thickness by 14% and insulin binding to partially purified hepatic membranes by 39% compared with control values. At 14 days following implantations, there were dramatic daily variations in plasma cortisol and prolactin levels in the control pigs and these rhythms were markedly altered in phase and amplitude in the bromocriptine-treated pigs. Bromocriptine reduced by 45, 20 and 13% the high levels of triglyceride, glucose, and cholesterol, respectively, that were found in control pigs near sunset. Plasma insulin concentrations did not vary during the day in control pigs and bromocriptine did not influence the insulin levels. The findings support important roles for a temporal synergism of cortisol and prolactin rhythms in maintaining hepatic lipogenic responsiveness to insulin. Bromocriptine treatment alters these hormonal relations and reduces lipid synthesis.
Animals↗
Properly timed injections of cortisol and prolactin produce long-term reductions in obesity, hyperinsulinaemia and insulin resistance in the Syrian hamster (Mesocricetus auratus).
Naturally obese female Syrian hamsters were injected daily with prolactin at 0 or 12 h after cortisol injections for 10 days while held in constant light. Controls were similarly injected with saline. Animals were then held on short daylengths (10 h light:14 h darkness) for 10 weeks. They were allowed free access to food and water from birth to time of death. Ten weeks after treatment, retroperitoneal fat stores, plasma concentrations of insulin and glucose, and hypoglycaemic responsiveness to exogenous insulin were determined. The control groups as well as the 12-h hormone treatment group were obese, hyperinsulinaemic and insulin resistant. However, the 0-h treatment dramatically reduced retroperitoneal fat stores (41-55%), plasma insulin concentration (60-70%) and the insulin to glucose ratio (63-68%) compared with controls. Values for these parameters in the 0-h treatment groups were similar to those of their lean litter-mates. Furthermore, the 0-h group but not the 12-h group was more sensitive than control animals to the hypoglycaemic effects of exogenous insulin at doses 0.2 and 2.0 U/kg body weight. These results demonstrate that timed daily injections of cortisol and prolactin in specific temporal relationships can produce marked reductions in obesity, hyperinsulinaemia and insulin resistance in the Syrian hamster that persist long after the termination of treatment. This study also suggests an important role for the interactions of circadian neuroendocrine systems in the regulation of these metabolic states.
Animals↗