Biomedical subjects

J R Gleason

Publications and source records attributed to J R Gleason.

At least 19 recordsLinked to original sources

PubMed2002

VMN/LHA functional inhibition in tumor-bearing rats suggests hypothalamic involvement in cancer anorexia.

Food intake is mainly controlled in the hypothalamus via a series of functionally related nuclei, including the ventromedial nucleus of hypothalamus (VMN) and the lateral hypothalamic area (LHA). Since food intake is the product of meal number and meal size, we investigated the role of the VMN and LHA in influencing these feeding indices and in mediating cancer anorexia in tumor-bearing (TB) rats, via temporarily inhibiting VMN or LHA. Adult male Fischer-344 rats (n = 23) inoculated with 106 MCA sarcoma cells were studied. When anorexia developed, rats were randomly assigned to stereotaxically located bilateral intra-VMN or intra-LHA microinjections of the neuronal blocker colchicine (CX; n = 6 each group) or saline (n = 6 and n = 5, respectively). Non TB rats (NTB; n = 7) served as controls. Food intake and feeding indices were recorded by a computerized device. At onset of anorexia, a reduction of meal number occurred, leading to reduced food intake. After inhibition of VMN activity by CX, meal number significantly increased, so that food intake increased and almost normalized. In contrast, intra-LHA microinjection of either CX or saline resulted in reduction of meal size, leading to reduced food intake and death. Findings suggest that VMN and LHA influence meal number and meal size, respectively. Since cancer anorexia mainly results from an initial reduction of meal number and the inhibition of VMN led to an increase in meal number, the early effect of tumor growth on VMN activity may be an early step leading to reduced food intake.

Animals↗

PubMed2000

Using information, motivational enhancement, and skills training to reduce the risk of HIV infection for low-income urban women: a second randomized clinical trial.

This randomized clinical trial evaluated an HIV-risk reduction (HIV-RR) intervention based on the information-motivation-behavioral skills model. At baseline, 102 women (M age = 29 years; 88% African American) completed a survey regarding HIV-related knowledge, risk perceptions, behavioral intentions, and risk behavior. Participants were then assigned to either the HIV-RR intervention or a health-promotion control group. Postintervention and follow-up data indicated that women in the HIV-RR program enhanced their knowledge and strengthened their risk reduction intentions relative to controls. Moreover, HIV-RR women who expressed "imperfect" intentions also increased their condom use, talked more with partners about condom use and HIV testing, and were more likely to have refused unprotected sex.

AIDS Serodiagnosis↗

PubMed2000

Use of the AUDIT and the DAST-10 to identify alcohol and drug use disorders among adults with a severe and persistent mental illness.

State Psychiatric Hospital outpatients (93 men, 69 women) diagnosed with a serious persistent mental illness (SPMI) completed the Alcohol Use Disorders Identification Test (AUDIT) and Drug Abuse Screening Test (DAST-10) by interview as part of a general health/behavior screening instrument. Responses to the AUDIT and DAST-10 were compared with criteria of current diagnosis and occurrence of symptoms in the last year for both alcohol and drug use disorders, respectively. Results showed that for both diagnosis and symptoms, AUDIT cutpoints of 7 and 8 had good sensitivity and specificity, and DAST-10 cutpoint of 2 was identified for both criteria. These and other findings suggest that both instruments have promising clinical utility when used with individuals diagnosed with an SPMI.

Adolescent↗

PubMed2000

Effects of intra-VMN mianserin and IL-1ra on meal number in anorectic tumor-bearing rats.

BACKGROUND: Tumor growth in animals and humans is associated with the onset of anorexia and reduced food intake. We previously demonstrated that the ventromedial nucleus of hypothalamus (VMN) plays a contributory role in mediating cancer anorexia. Because serotonin and interleukin-1 (IL-1) are putative mediators of cancer anorexia, we hypothesized that their influence on food intake during tumor growth might occur via their action within the VMN. METHODS: To test this hypothesis, 12 Fischer rats injected subcutaneously with 10(6) viable MCA sarcoma cells (TB rats) and their nontumor-bearing controls (NTB, n = 13) were studied. When anorexia developed, TB and NTB rats received bilateral intra-VMN microinjections of the serotonin antagonist mianserin (200 nmol) or the IL-1 receptor antagonist (IL-1ra, 25 ng). Food intake and its determinants of meal number and size were continuously recorded via a computerized device. RESULTS: In NTB rats, intra-VMN mianserin did not affect food intake, whereas after IL-1ra or vehicle a momentary decrease in food intake due to a predominant reduction of meal size occurred. In TB rats, intra-VMN mianserin or IL-1ra selectively increased meal number, leading to improved food intake. CONCLUSIONS: Data suggest that intra-VMN serotonin and IL-1 are involved in influencing cancer related anorexia.

Animals↗

PubMed2000

Comparison of early feeding pattern dynamics in female and male rats after reversible ventromedial nucleus of hypothalamus block.

BACKGROUND: In the hypothalamus, a number of interconnected foci, including the ventromedial nucleus of hypothalamus (VMN), interact to control food intake (FI). FI is a function of meal number (MN) and meal size (MZ). Because gender differences exist in feeding patterns, we aimed at investigating the role of the VMN in determining the relationship of MZ and MN in female and male rats. METHODS: FI and feeding patterns of 10 female and 12 male Fischer-344 rats were studied after VMN block, achieved via stereotaxically located intra-VMN microinjection of the neuronal blocker, colchicine (0.32 microgram dissolved in 50 nL of isotonic injectate and instilled on each side into the VMN). RESULTS: After colchicine injection in normal female rats, an immediate and significant increase in FI occurs as a result of the following: 1) increased MZ in dark and light phases and 2) increased light phase MN with consequent loss of the normal diurnal cycle in FI. Recovery of feeding cycle and normal vaginal smear pattern occurred by study's end. In normal male rats, VMN block resulted in the following: 1) an increase in FI resulting from increased MN occurring predominantly during the light phase, thereby 2) disrupting the usual light/dark feeding cycle. CONCLUSIONS: Sexual differences in regulation of FI occur after temporary reversible VMN block: in female rats, MZ is more sensitive to experimental modulation, whereas in male rats it is MN.

Animals↗

PubMed1999

Lack of influence of hysterectomy on meal size and meal number in Fischer-344 rats.

Based on our previous observation that, when eating the same amount of food per 100 g b.wt., male rats gain five to seven times more weight than females who have an estrous cycle every 4 to 5 days, we questioned whether lower weight gain seen in female rats could be the result of increased energy cost in preparing endometrium for anticipated fertilization. Because the uterus modulates estrogenic effects on other hormone-dependent behaviors, for example, sexual receptivity and lordosis, we performed this study to determine if estrogen-mediated cyclical changes in food intake and feeding pattern occur after hysterectomy. Fifteen female Fischer 344 rats were randomized during the estrous phase to either hysterectomy with ovarian preservation or sham operation. A rat eater meter was used to continuously measure food intake, meal number, and meal size for two estrous cycles before and four cycles after surgery. Both groups showed the estrous phase linked cycling in meal number, meal size, and food intake. No differences existed between the two groups in these indices either before or after surgery. No differences existed between groups in rate of body weight gain after surgery, 0.95 +/- 0.13 g/day in hysterectomized and 0.77 +/- 0.1 g/day in sham-operated rats. We conclude that hysterectomy has no effect on rate of weight gain, food intake, and estrus linked cyclical feeding pattern in Fischer 344 rats.

Animals↗

PubMed1999

Effect of operative stress on food intake and feeding pattern in female rats.

Effects of operative stress on food intake, meal size, and meal number were measured in 15 female rats before and after jugular vein catheterization. All rats had 5-d estrous cycles which correlated with cyclical feeding patterns that were most prominent during dark phase eating. In proestrous, meal number peaked (30.3+/-1.32), and meal size reached a nadir (0.33+/-0.02 g) with some corresponding change in food intake (9.8+/-0.38 g). Following operation on day 11, the cyclical variation of food intake, meal number, and meal size with estrous cycle was lost for the first 3 d, as was the diurnal rhythm in food intake. Eight rats recovered their dark phase feeding pattern by day 17 (recovered group), while 7 had not done so even by day 24 (non-recovered group). Food intake decreased to 40% of baseline in the recovered group and to 25% in the non-recovered group on day 11, increasing to 70% by day 14 in both groups and matching preoperative levels by day 17. Similar postoperative decreases were observed in meal number and meal size. Light phase feeding was increased, the ratio of day to night food intake being three times preoperative levels even at day 24. Preoperatively, non-recovered rats were similar to the recovered rats in all feeding indexes and continued to have estrous cycling in vaginal smears postoperatively. In the non-recovered rats, meal size more than doubled and meal number was depressed by 47% of preoperative levels and remained low until the end of the study. We conclude that operative stress disrupted cyclical and diurnal rhythms in food intake. In female rats, meal size is the first index to recover, increasing temporarily to maintain food intake.

Animals↗

PubMed1997

Acute adaptive changes in food intake pattern following olfactory ablation in rats.

We determined whether acute compensatory feeding pattern changes after bulbectomy persist on a chronic basis, or whether physiological adaptation occurs to normalize acute changes. Rats were randomized to olfactory bulbectomy or sham operation; all had jugular vein catheterization. Food intake, meal number and size were studied during infusion of parenteral nutrients providing 100% daily caloric intake (PN-100) to minimize post-ingestive effects. Rats were randomly assigned to acute (from day 14 after operation, PN-100 infused for 4 days, followed by 4 days of saline infusion) or chronic study (PN-100 infused for 4 days from day 40, followed by 4 days of saline infusion). After olfactory ablation, acutely decreased meal size was offset by increased meal number, but 40 days after, baseline differences between meal size and number no longer existed. No qualitative differences in response to PN-100 were noted between acute and chronic groups. Findings suggest a functional adaptation of food intake regulatory mechanism between 14 and 40 days after bulbectomy.

Adaptation, Psychological↗

PubMed1996

In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists.

After more than two decades of nutritional awareness, we designed a prospective study to determine whether malnutrition is still a significant issue in hospitalized patients. Patients admitted to an intensive care unit (ICU) were divided into well-nourished and malnourished groups, according to their nutritional status as assessed by serum albumin level and weight/height ratio. Severity of illness, as assessed by the Therapeutic Intervention Scoring System (TISS), was used to further stratify the study population. All patients were followed clinically until discharge or death and their outcome recorded. Of 129 patients studied, 43% were malnourished. Length of hospital stay (p = n.s.), incidence of complications (p < 0.01), and number of patients not discharged from hospital (p < 0.05) were greater in the malnourished patients than in the well-nourished. In patients with less severe degrees of illness, the existence of malnutrition led to a worse outcome than in sicker patients. To further assess the clinical setting in which hospital-related malnutrition develops or is exacerbated, postoperative patients admitted to the ICU (n = 66) were also studied in a nutritional survey; the results of this survey indicate that: (a) the incidence of malnutrition in the surgical population is similar to that in the whole study population, and (b) hospital-related malnutrition in surgical patients mainly develops during their preoperative stay in general wards. Whereas our conclusion that patients' outcome is adversely affected by a poor nutritional status is not new or startling, malnutrition continues to be a persistent problem in hospitalized patients, which can be readily identified using simple and easily available indices and, furthermore, readily treated.

Adolescent↗

PubMed1996

The gut-brain brain-gut axis in anorexia: toward an understanding of food intake regulation.

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes--thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

Animals↗

PubMed1996

Innervated liver plays an inhibitory role in regulation of food intake.

BACKGROUND: With the onset of eating, the associated rise of dopamine in the lateral hypothalamus (LHA-DA) is thought to regulate quantity of food consumed per meal. Early release of LHA-DA induced by eating is facilitated by oronasal stimulation; we propose that the subsequent LHA-DA response induced by nutrients in the portal vein is dampened by the innervated liver. This was tested by measuring LHA-DA in normal rats: during parenteral feeding to bypass oronasal stimulation, while eating during parenteral feeding, and while eating only. METHODS: Rats had either total liver denervation or sham operation, with placement of a jugular vein catheter and LHA-DA microdialysis cannula. After a 3-week recovery period total liver denervated rats were randomized to parenterally fed, food only, and parenteral plus food groups each with sham-operated controls in which LHA-DA was measured. RESULTS: No difference in LHA-DA release in food only groups occurred between total liver denervated or sham-operated rats. A significantly higher rise in LHA-DA was observed in total liver denervated versus sham-operated rats in parenterally fed (129% +/- 4% versus 116% +/- 2%; p < 0.05) and parenteral plus food (151% +/- 4% versus 134% +/- 4%; p < 0.05) groups. CONCLUSIONS: In total liver denervation versus sham operation, an increase in LHA-DA release occurs during parenteral feeding and eating during parenteral feeding, suggesting that innervated liver inhibits LHA-DA release.

Animals↗

PubMed1996

Cracking the riddle of cancer anorexia.

During tumor growth, anorexia and reduced food intake are among the major causes leading to malnutrition and eventually cachexia, which negatively affect patients' outcome. Consistent evidence from our laboratories in rats and humans indicates a key role for ventromedial hypothalamic (VMH) serotonergic system in the development of cancer anorexia. Thus, we postulated that during cancer, increased plasma tryptophan levels (the precursor of serotonin) lead to increased cerebrospinal fluid tryptophan concentrations and increased VMH serotonin synthesis, which then mediates the occurrence of anorexia. However, recent data strongly suggest that factors other than tryptophan supplied to the central nervous system might be involved in the pathogenesis of reduced food intake during tumor growth. Particularly, a significant role appears to be played by interleukin-1 (IL-1). We recently showed that IL-1 infusion in normal rats causes changes in food intake and its determinants, meal number and meal size, similar to those characterizing cancer anorexia, thus supporting the involvement of this cytokine in the development of anorexia. Interestingly, IL-1 and the VMH serotonergic system appear to be closely linked: peripherally infused IL-1 increases brain tryptophan and serotonin concentrations, while intracerebrally infused IL-1 increases neuronal firing rate and serotonin release. We therefore hypothesize that during tumor growth, increased production/secretion of IL-1 occurs, which facilitates the tryptophan supply to the brain. IL-1 can then also act on the VHM itself, where IL-1 receptors exist, to increase its neuronal activity and serotonin release. In other words, we believe that centrally acting IL-1 increases hypothalamic neuronal firing rate and serotonin release, while peripherally acting IL-1 is critical in supplying the hypothalamus with the precursor, tryptophan, in order to maintain the high rate of serotonin synthesis. Also, additional factors recently proposed as mediators of anorexia (including neuropeptide Y and nitric oxide) appear to be part of the hypothesized pathogenic mechanism.

Animals↗

PubMed1996

Comparison of long-term feeding pattern between male and female Fischer 344 rats: influence of estrous cycle.

We studied the effect of gender on food intake, meal number, and meal size in eight 10-wk-old female and seven age-matched male Fischer 344 rats for 44 consecutive days. Although food intake (g/100 g body wt) was similar in males and females (5.42 +/- 0.10 vs. 5.13 +/- 0.13 g food.day-1.100 g body wt-1, respectively; not significant), weight gain in males was approximately seven times greater than in female rats (1.49 +/- 0.07 vs. 0.21 +/- 0.03 g/day, respectively; P < 0.001). During this time, males had a relatively constant food intake. They increased their meal size but decreased their meal number. In female rats, food intake was relatively stable for the duration of the study, despite cyclically and reciprocally recurring changes in meal number and meal size, which are synchronized with the estrous cycle. Data confirm that net food intake is a dynamic process and suggest that, in the rat, the homeostasis of food intake in response to external as well as internal stimuli is maintained via the modulation of meal number and size.

Animals↗

PubMed1995

Temporal changes in meal number and meal size relationship in response to rHu IL-1 alpha.

Peripherally infused interleukin-1 reduces food intake. Its temporal and selective effects on meal number and meal size were investigated in seven rats continuously infused for 3 days with recombinant human interleukin-1 alpha (rHu IL-1 alpha; 3 micrograms day-1, i.v.). Food intake decreased significantly during the first two infusion days, and was brought about by first the early reduction of meal number, followed by meal size with a 1 day delay. The primary effect of rHu IL-1 alpha was seen during the dark cycle. After the infusion was stopped, meal number recovered most quickly, followed by a lag in recovery of meal size. We conclude that rHu IL-1 alpha influenced food intake primarily via an effect on meal number, which responds more rapidly than a decrease in meal size, thereby inducing an immediate decrease in food intake.

Animals↗

PubMed1995

The effects of risedronate on canine cancellous bone remodeling: three-dimensional kinetic reconstruction of the remodeling site.

To investigate the dose-dependent effects of risedronate on cancellous bone remodeling, adult female beagle dogs were treated with either placebo, 0.1, 0.5, or 2.5 mg/kg/day of risedronate orally in an intermittent cyclic regimen (7 days on 21 days off), repeated three times. Iliac cancellous bone samples were subjected to histomorphometric analysis and three-dimensional (3-D) kinetic reconstruction of the remodeling site was performed. In the 0.1 mg/kg dose group, resorption and activation indices were no different from the placebo group. However, wall thickness was increased resulting in a positive bone balance at the level of the remodeling unit. In the 0.5 and 2.5 mg/kg dose groups, a dose-dependent reduction in activation frequency and tissue level bone formation was observed. Resorption rates were also significantly decreased, 60% and 80% for the 0.5- and 2.5-mg/kg groups, respectively. An approximate 25% reduction in final erosion depth was noted in both these groups. Analyses of the growth curves of the bone packet confirmed that the kinetics of the growth of a completed packet were different in the 0.5- and 2.5-mg/kg dose groups compared with placebo. These changes were associated with a significant increase in the final wall thickness in both groups indicating no net impairment of osteoblast function. These increases in wall thickness in combination with the reductions in final erosion depth in the 0.5 and 2.5 mg/kg groups resulted in a significant dose-dependent positive bone balance. This pharmacological profile suggests that risedronate may be of therapeutic utility in the treatment of metabolic bone diseases where reductions in activation frequency and resorptive cell activity at the level of the remodeling unit are a therapeutic goal.

Administration, Oral↗

PubMed1995

Effects of TPN on brain, liver, and food intake in rats.

Postulating that total parenteral nutrition (TPN) has a direct metabolic effect in the brain which may be similar to that in the liver, we studied the effects of TPN on brain glycogen and triglyceride in rats. Control rats (n = 24) received normal saline via jugular catheter for 18 days; TPN rats (n = 24) had normal saline for 10 days and then TPN-100 for 4 days, followed by normal saline for 4 more days. TPN-100 (caloric ratio glucose: fat:amino acid = 50:30:20) provided 100% of the rat's daily caloric needs. Chow and water were available ad libitum during the study. Eight rats from each group were sacrificed after 1 and 4 days of TPN-100, and 4 days after stopping TPN-100. Glycogen in brain and liver glycogen, triglyceride, and glycogen synthetase and phosphorylase were measured, as were plasma glucose and insulin. Data were evaluated using Student's t test. With TPN, the following occurred: (a) an 85% decrease (P < 0.05) of spontaneous food intake; (b) an elevated plasma glucose; (c) a three- to fivefold increase (P < 0.01) in plasma insulin; (d) a 23% increase (P < 0.05) in whole brain glycogen but a 22-33% decrease (P < 0.05) in liver glycogen; (e) liver glycogen synthetase and phosphorylase activity were unchanged while whole brain glycogen synthetase activity decreased by 27% (P < 0.05) and phosphorylase activity increased by 10-16%; and (f) whole brain triglyceride content did not change, although there was a 155-241% increase (P < 0.01) in liver triglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of erythropoietin on renal excretion of a sodium load.

To determine whether erythropoietin alters the renal excretion of a sodium load in humans, we administered either erythropoietin (150 units/kg) or vehicle intravenously in a randomized crossover design to six normal white men on day 4 of a controlled sodium diet. After erythropoietin administration, the subjects were given 2 L normal saline solution intravenously over 4 hours. All urine was collected for 4 days after drug administration. Serum sodium and creatinine levels and blood pressure were determined 0, 4, 8, and 24 hours after drug administration. Peripheral renin activity and aldosterone levels were determined 0, 4, and 8 hours after drug administration. Erythropoietin significantly decreased total sodium excretion during the 4 days after drug administration (erythropoietin = 784 +/- 46 mEq/4 days versus control = 840 +/- 41 mEq/4 days; p < 0.001). Erythropoietin did not alter creatinine clearance, blood pressure, or the changes in plasma renin activity and aldosterone caused by the saline load. We conclude that erythropoietin decreases urine sodium excretion after a sodium load in normal human subjects without altering glomerular filtration rate, blood pressure, or plasma renin activity.

Analysis of Variance↗

PubMed1994

Synergistic effect of rhTNF-alpha and rhIL-1 alpha in inducing anorexia in rats.

To investigate whether there is a synergistic effect of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) and recombinant human interleukin-1 alpha (rhIL-1 alpha) in inducing anorexia, 32 rats with jugular catheters were studied (8 rats/group): controls received normal saline; the IL-1 group received rhIL-1 alpha (10 micrograms/kg); the TNF group received rhTNF-alpha (30 micrograms/kg); and the IL-1 + TNF group received the same concentration of both rhIL-1 alpha+rhTNF-alpha for 3 days; solutions were then switched to normal saline. No significant decrease in light- and dark-phase food intake occurred during infusion of subeffective rhTNF-alpha. Food intake was decreased on the first rhIL-1 alpha infusion day because of a decreased meal number during the dark phase. A significant decrease in food intake occurred with combined infusion of rhIL-1 alpha+rhTNF-alpha because of a reduction in meal number during dark phase and meal size during light phase. Our results show that rhIL-1 alpha and rhTNF-alpha, when administered concurrently, had a synergistic effect in inducing anorexia, suggesting that low concentrations of these cytokines as produced endogenously may have potential effects on other biological functions in vivo.

Animals↗