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We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (GK) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 mug/mL and 5.0 mug/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization.

We present the results of the first dedicated survey for 22 GHz H2O maser emission in dwarf galaxies outside of the Local Group, with the aim of discovering disc masers. Studies of disc masers yield accurate and precise measurements of black hole (BH) mass, and such measurements in dwarf galaxies would be key to understanding the low-mass end of BH–galaxy coevolution. We used the Green Bank Telescope to survey 100 nearby (z  ≲ 0.055) dwarf galaxies (M * ≲ 109.5 M⊙) with optical emission line ratios indicative of accretion on to a massive black hole. We detected no new masers down to a limit of ∼12 mJy (5σ). We compared the properties of our sample with those of ∼1850 known detections and non-detections in massive galaxies. We find, in agreement with previous studies, that masers are preferentially hosted by Seyferts and highly obscured, [O  iii ]-bright active galactic nuclei (AGNs). Our sample has fewer Seyferts, is less obscured, and is [O  iii ]-faint. Though the overall maser detection rate is ∼3 per cent in massive galaxies, the predicted rate for our sample, weighted by its optical properties, is ∼0.6–1.7 per cent, corresponding to a probability of making no detections of ∼20–50 per cent. We also found a slight increase in the detection rate with increased stellar mass in previously surveyed galaxies. However, further observations are required to discern whether there is an intrinsic difference between the maser fraction in active dwarf galaxies and in their massive counterparts for the same AGN properties. [ABSTRACT FROM AUTHOR]

Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cyclo (his-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE alone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors.

Since rabbit prostate extract strongly stimulated intestinal zinc absorption and improved the diabetic condition of streptozotocin-induced diabetic rats, we examined the effects of 200 mg bovine prostate powder supplemented with 20 mg zinc (Pro-Z) on the clinical manifestations of older male patients with type II diabetes. Twenty-two male patients who received Pro-Z capsules two to four times per day for 3 months showed reduced mean fasting blood glucose levels from 202 to 169 mg/dL, hemoglobin A1C-(HbA1C) concentrations from 12.2% to 9.5%, and mean values for the 3-hour area response above the fasting glucose concentration (TAFGC) from 141 to 102 mg glucose/dL/h. In eighteen patients who received placebo, mean values for fasting blood glucose decreased from 167 to 165 mg/dL and HbA1C from 10.4% to 10.2%, and for TAFGC increased from 121 to 126 mg glucose/dL/h. No detrimental changes occurred in the liver and kidney function of patients receiving either Pro-Z or placebo. However, blood cholesterol and low-density lipoprotein in patients receiving Pro-Z decreased slightly, whereas values in the placebo group tended to increase. The mean fasting plasma insulin decreased 15.5 to 13.8 microU/mL in subjects given Pro-Z, while the zinc concentration increased from 1.21 to 1.39 microg/mL. In contrast, the mean value for plasma insulin in the placebo group changed from 14.4 to 15.4 microU/mL (worsened), and for zinc, from 1.24 to 1.30 microg/ml. Interestingly, fasting urinary glucose concentrations in subjects given Pro-Z decreased from 1,249 to 378 mg/dL, whereas in those given placebo the values changed from 877 to 778 mg/dL. Since plasma zinc concentrations in both the placebo and the Pro-Z group were normal, these results suggest that biochemical constituents in the prostate including zinc may be involved in controlling glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

The present study examined the effects of progressive relaxation training and EMG biofeedback on acute glucose disposal in diabetic subjects, as measured by glucose tolerance and three other measures of diabetic metabolic control. Twenty subjects with non-insulin-using Type II diabetes took part in progressive relaxation training and EMG biofeedback in a pre-post treatment versus wait-list experimental design. Treatment effects were assessed on glucose tolerance along with three measures of diabetic control: fasting blood glucose, two-hour postprandial blood glucose, and fructosamine. Stress reduction and relaxation was assessed with two physiological measures and two subjective questionnaires. The training program produced significant reductions in stress, as measured by State Anxiety, and significant changes in physiological measures of muscle activity and skin conductance compared to the control condition. However, no changes were found in glucose tolerance (while practicing relaxation) nor in any of the three measures of general diabetic metabolic control. The major implication of this study is that relaxation training does not appear to directly improve diabetic control in mildly stressed non-insulin-using Type II diabetic patients.

Objectives: Despite the diversity of wheelchair cushions currently in clinical use, pressure on bony prominences continues to be a major problem for wheelchair-bound patients, and the incidence of pressure ulcers remains high. No static surface has been reported to reduce resting pressure under the ischial tuberosities to below that of capillary pressure, which may well be the threshold for inducing tissue damage. An entirely new form of seating was designed to decrease absolute pressure using a prosthetic fitting technique analogous to a below-the-knee prosthesis., Design: A repeated measures randomized design was used to test differences between the experimental (TCS) and three other standard cushions., Setting: A Veterans Medical Center outpatient service., Patients: Wheelchair-bound volunteer subjects, n = 47, were selected who weighed more than 60kg., Main Outcome Measures: Pressures were measured by a standard air pressure pad and also by a computer-linked array of pressure transducers. The grid was standardized and used to generate topographic maps for each site over time. These data were used to measure the seating interface pressures., Results: There was a significant main effect of cushion over site, F = 131 for left ischial tuberosity. Pressure were lowest while patients sat on the experimental seat and differences were significant at all time points. Using 1psi as presumed capillary pressure, frequency of success at achieving this pressure threshold was greatest for the experimental seat, p < .001. This difference persisted throughout the 30 minutes of testing., Conclusions: A computerized pressure grid was developed that allowed evaluation of anatomically localized pressures. The prosthetically designed TCS displays lower seating pressures than any other cushion tested. Consistent and sustained pressures were below the postulated threshold for tissue damage.

Purpose: To examine the effects of advanced age and diabetes on the response to standard tests of cardiovascular reflexes., Design: Group comparison., Setting: Psychophysiology laboratory, Department of Veterans Affairs Medical Center., Patients: Sixteen elderly male (67-81 years old) non-insulin dependent diabetic subjects without hypertension and nine elderly male (63-77 years old) controls., Main Outcome Measures: Continuous (beat-by-beat) measures of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance were studied during tests of Valsalva maneuver, deep breathing, and postural change from sitting to standing., Results: In comparison with elderly controls, the diabetic patients showed altered cardiovascular responses in measures of heart rate variability during Valsalva and standing. None of the subjects evidenced frank postural hypotension, but there was a greater fall in diastolic blood pressure immediately after standing for the diabetic patients compared with the controls. There was also a significant relationship between this response and decreased heart rate variability during Valsalva., Conclusions: Older type II diabetic patients compared with healthy controls had mild cardiovascular abnormalities. These results parallel those of studies comparing younger diabetics and controls.

The potential roles of adrenergic and noradrenergic terminals in the hypothalamic paraventricular nucleus in the regulation of blood glucose and free fatty acids, the two major metabolic fuels, were examined. Corticosterone was also measured, both to assess the specificity of any effects for metabolic fuels, and because endogenous catecholamines in this site have previously been implicated in corticosterone regulation. In the first experiment adult male albino rats having chronically implanted guide cannulae aimed at the hypothalamic paraventricular nucleus or the caudate nucleus received microinjections of the agonists methoxamine (alpha 1), clonidine (alpha 2), and isoproterenol (beta) (0, 10, 30, 100 nmol/500 nl), and blood samples were taken from the tail tip. In the second experiment a different set of rats received 30 nmol clonidine or vehicle subcutaneously instead of brain microinjections. Intracranial clonidine and isoproterenol produced marked and moderate hyperglycemia, respectively; methoxamine did not alter glucose. For neither clonidine nor isoproterenol was there any difference in hyperglycemia as a function of microinjection site; also, subcutaneous clonidine injections produced the same peak glucose response as was found after both paraventricular and caudate nucleus microinjections of the same dose. Free fatty acid levels were increased by clonidine and isoproterenol, but slightly suppressed by methoxamine; the alpha agonist effects, but not the beta agonist effect, were greater after paraventricular microinjections than after caudate microinjections. Corticosterone was increased by both alpha agonists after paraventricular but not after caudate nucleus microinjections; beta agonist microinjections into the paraventricular and caudate nuclei produced equivalent corticosterone elevations. These results suggest that most, if not all, of the hyperglycemic effects of alpha and beta adrenergic agonist microinjection into the paraventricular nucleus can be ascribed to leakage of the material into the vasculature, with subsequent action at a distant site. In contrast, all 3 agonists seem capable of acting within the brain to alter free fatty acid levels. The effects on corticosterone of both the alpha 1 and alpha 2 agonists, but not the beta agonist, also appear due, at least in part, to actions within the brain. Previous suggestions that catecholamine terminals in the hypothalamic paraventricular nucleus are directly and strongly involved in metabolic fuel regulation may require reconsideration.

Microinfusion of bombesin into the preoptic area (POA) has previously been shown to reduce core body temperature and feeding in rats that are food-deprived or made hypoglycemic with insulin. The present study determined the metabolic fuel state of rats under these experimental conditions. In addition, changes in plasma metabolic fuels following the microinfusion of bombesin (50 ng/0.25 microliters) into the POA were evaluated. Rats (n = 8) were tested under conditions of food satiation, food deprivation (20 h), and insulin pretreatment (10 U/kg). Prior to peptide infusion, food-deprived rats exhibited the expected elevation in free fatty acids coupled with a small decline in plasma glucose. Insulin treatment resulted in hypoglycemia which persisted for at least 120 min. Following bombesin infusion, free fatty acids and corticosterone levels were elevated in food-sated rats. Food-deprived rats exhibited elevation in plasma glucose, free fatty acids, and corticosterone following peptide infusion. In insulin-treated rats, bombesin attenuated the hypoglycemia observed in controls and increased corticosterone levels. These findings suggest that bombesin-like peptides localized within the POA may participate in the regulation of metabolic fuels.

Bombesin is a particularly potent hyperglycemic agent when administered intraventricularly or intracisternally in the rat. Because bombesin-like immunoreactivity is found in several forebrain regions implicated in glucoregulation, the ability of direct hypothalamic microinfusions of this peptide to affect serum metabolic fuel levels was tested. Three experiments, using anesthetized, acutely infused rats, or unanesthetized rats with chronic intracranial implants, showed that microinfusion of bombesin into the hypothalamic paraventricular nucleus caused significant, dose-related increases in serum glucose; infusions into the lateral hypothalamus or the caudate nucleus were ineffective. Infusions into the ventromedial nucleus significantly elevated glucose only in acutely anesthetized rats. In unanesthetized rats with chronic intracranial cannulae, bombesin infusions into all 3 hypothalamic sites, but not the caudate-putamen, significantly elevated blood free fatty acids, while only infusions into the paraventricular nucleus caused significant dose-related increases in blood corticosterone. The results demonstrate that the paraventricular nucleus is a sensitive site for bombesin-induced elevation of blood glucose, free fatty acids, and corticosterone. They also imply that the bombesin binding sites and immunoreactive terminals previously identified in these regions may be involved in the central regulation of circulating metabolic fuel levels and the pituitary-adrenal axis, and that the effects of acute surgery may augment the hyperglycemic response to intrahypothalamic bombesin administration.

To examine age-related changes in responsiveness to environmental novelty, 3-, 12-, and 24-month-old male Fischer 344 rats were maintained on a restricted diet and exposed to a modified open field for 10 min on each of 10 consecutive days. On the first day of testing, animals of all groups showed equal amounts of rearing. While the 3-month animals continued to show approximately the same levels of rearing until the 8th day, by day 5, the older groups (12- and 24-month) had significantly reduced their rearing. Conversely, grooming was initially highest among the 24-month-old animals. While 3- and 12-month rats showed habituation of grooming, the oldest animals failed to habituate their grooming response by day 5. By day 10, there were no significant differences among the groups in either rearing or grooming. Although food was available in the center of the modified open field, there was little eating and there were no differences among groups. However, all animals did eat quickly when food was made available in their home cages. Thus, all animals displayed a profile of stress-related responses to open field exposure. Plasma corticosterone levels likewise were elevated in the modified open field. Some, but not all, components of this response profile habituated over the 10 days of exposure. Three-month-old animals responded to the novelty predominantly by rearing and 24-month animals predominantly by grooming. This suggests that with aging, locomotor responses to stress are replaced by a more self-directed form of displacement activity.

Aging is associated with a considerable number of alterations in function of the autonomic nervous system and with systems involved in the control of cardiovascular response to postural changes. However, these alterations themselves do not generally lead to symptomatic orthostatic hypotension. In combination with other factors, older patients can develop marked problems with orthostatic hypotension--notably, certain drug regimens, some degree of underlying heart failure, or such common geriatric illnesses as parkinsonism and diabetes. Treatment regimens must be designed to minimize side effects. While aggressive pharmacologic treatment may be helpful for young patients, among the elderly physical therapy or behavioral maneuvers may promote the most benefit with least risk. The simplest first step, however, is to focus on possible iatrogenic causes and eliminate them.

Aging alters motor performance. Changes in adrenergic systems also occur and may be involved in altered motor function. Since beta-adrenergic input is prominently involved in cerebellar control, the current study investigated the relationship between cerebellar beta-adrenergic status and motor function in old (27 month) and mature (10 month) C57BL mice. Plank balance, photocell box activity and novelty-induced locomotion were all greater in mature compared to old mice (P less than 0.01) as was beta-adrenergic receptor density. Beta-adrenergic receptor density, but not receptor affinity for antagonist, was highly correlated to these measures of motor function when results from both groups of animals were analyzed: Plank balance (R = 0.80, P less than 0.01); locomotion in an open field (R = 0.60, P less than 0.01) and in a photocell box (R = 0.59, P less than 0.02). Aging alters cerebellar motor function and part of this dysfunction is correlated with beta-adrenergic receptor density.

To determine the effects of age on nocturnal fuel regulation, we measured spontaneous plasma glucose and free fatty acid (FFA) levels as well as counterregulatory hormones in healthy young (n = 9, mean age 26 +/- 3 years) and old (n = 10, mean age 69 +/- 3 years) men from midnight to 8 AM. FFA levels rose from midnight (660 +/- 80 mEq/L for young subjects, 545 +/- 55 mEq/L for old) to a peak mean level of 866 +/- 110 mEq/L at 3 AM in young and 713 +/- 120 mEq/L at 1:30 AM in old (P less than .05). FFA levels declined thereafter for both groups. FFA levels were lower in older subjects (P less than .05) but integrated glucose (P less than .05) and insulin (P less than .05) levels were higher. FFA levels were inversely related to integrated insulin (r = -0.46, P less than .05) and glucose concentrations (r = -0.66, P less than .05). Integrated insulin levels were significantly higher in older subjects, which may explain the lower FFA levels as may lower growth hormone levels in the older subjects. While fasting glucose responsivity to endogenous insulin is impaired in healthy older men, the FFA response appears to be preserved.

This is the author's fifth revision of a geriatrics bibliography. Approximately one-third of the previous references have been replaced by more current or more delimited articles. Because the literature pertinent to geriatrics has continued to grow ever more rapidly, it has been necessary to omit many informative articles from the bibliography. Preference is given to recent publications; almost all of the reference data from the past four years. Some articles were selected to highlight current controversies or changes in viewpoint. Most of the references deal specifically with an elderly patient population, though few use a multidisciplinary approach. Studies of the elderly are confounded by concomitants of aging frequent but not universal in our society: inactivity, obesity, malnutrition, and psychosocial trauma. The articles cited are primarily concerned with medical ailments of the elderly; legal, ethical, and sociological topics receive more limited coverage. The references are divided into categories. The first set (I) deals with some possible causes of aging; the second (II) with physiologic decline accompanying aging; the third (III) with the atypical and nonspecific characteristics of illness among geriatric patients; the fourth (IV) with the elderly and society; and the fifth (V) with care options. The remainder of the references are cited by pertinent medical specialty. Within each category, references are divided by disease process. Articles are further subgrouped by aspects of those diseases such as evaluation or therapy.