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Biomedical subjects

M M Meguid

Publications and source records attributed to M M Meguid.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hypothalamic dopamine and serotonin in the regulation of food intake.

Because daily food intake is the product of the size of a meal and the frequency of meals ingested, the characteristic of meal size to meal number during a 24-h light-dark cycle constitutes an identifiable pattern specific to normal states and obesity and that occurs during early cancer anorexia. An understanding of simultaneous changes in meal size and meal number (constituting a change in feeding patterns) as opposed to an understanding of only food intake provides a more insightful dynamic picture reflecting integrated behavior. We have correlated this to simultaneous changes in dopamine and serotonin concentrations and to their postsynaptic receptors, focusing simultaneously on two discrete hypothalamic food-intake-related nuclei, in response to the ingestion of food. The relation between concentrations of dopamine and serotonin limited to the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) as they relate to the influence of meal size and meal number during the hyperphagia of obesity and anorexia of cancer as measured in our experiments are discussed. Based on these data, conceptual models are proposed concerning: 1) an "afferent-efferent neurotransmitter unit," with facilitatory or inhibitory neuropeptide properties to generate an appropriate neuroendocrine and neuronal response that ultimately modifies food intake; 2) initiation and termination of a meal, thereby determining the number and size of a meal under normal conditions; and 3) a schema integrating the onset mechanism of cancer anorexia. Nicotine is used as a tool to further explore the relation of meal size to meal number, with a focus on simultaneous changes in dopamine and serotonin concentrations in the LHA and VMN with the onset of acute anorexia of nicotine infusion and acute hyperphagia of nicotine cessation. Data concerning the role of sex-related hormones on dopamine and serotonin with regard to the LHA and VMN in relation to the modulation of food intake are also presented.

Animals↗
PubMed2000

VMN dopaminergic graft and feeding pattern in obese Zucker rats.

OBJECTIVE: To study the role of dopamine in the ventromedial hypothalamus (VMN) in the regulation of meal size and meal number during obesity. METHODS: Embryonic mesencephalic cells rich in dopaminergic neurons from lean rats were grafted into the VMN of obese Zucker rats. Since food intake is the product of meal size and number, these variables were measured using a rat 'eater meter'. Dopamine and serotonin concentrations in the VMN were assayed in grafted and control rats via in vivo microdialysis and HPLC two months after transplantation. RESULTS: Food intake increased in grafted rats due to an increase of both meal size and meal number 2 weeks after implantation and to an increase of meal size with insufficient compensatory decrease of meal number 2 months after transplantation. Grafted rats showed higher absolute dopamine and lower serotonin concentrations in the VMN. CONCLUSION: It would appear that an increase of dopamine and a decrease of serotonin in the VMN of grafted obese rats may correlate with increase in meal number and meal size, respectively. Since obese Zucker rats usually display an enlarged meal size, we deduce from the data that chronically elevated VMN dopamine and low serotonin are involved in producing the large meal size observed during obesity.

Animals↗
PubMed2000

VMN hypothalamic dopamine and serotonin in anorectic septic rats.

During sepsis, catabolism of proteins and associated changes in plasma amino acids occur. Tryptophan and tyrosine, and their derivatives serotonin (5-HT) and dopamine (DA), influence hypothalamic feeding-related areas and are associated with the onset of anorexia. We hypothesized that anorexia of sepsis is associated with changes in serotonin and dopamine in the ventromedial nucleus (VMN) of the hypothalamus. The aim of this study was to test our hypothesis by measuring intra-VMN changes of these two neurotransmitters at the onset of anorexia during sepsis. Fischer 344 male rats had an intracerebral guide cannula stereotaxically implanted into the VMN. Ten days later, in awake, overnight-food-deprived rats, a microdialysis probe was inserted through the in situ VMN cannula. Two hours thereafter, serial baseline serotonin and dopamine concentrations were measured. Then cecal ligation and puncture to induce sepsis or a control laparotomy was performed under isoflurane anesthesia. VMN microdialysis samples were serially collected every 30 min for 8 h after the surgical procedure to determine 5-HT and DA changes in response to sepsis. During the hypermetabolic response to sepsis, a strong association occurred between anorexia and a significant reduction of VMN dopamine concentration (P < 0.05; constant rate of dopamine decrease in the Study group of 0.99 pg per 2 h); no changes occurred in 5-HT in association with anorexia of sepsis. Six hours after operation, a single meal was offered for 20 min to assess the response of neurotransmitters to food ingestion. Food intake was minimal in anorectic septic rats (mean size of the after food-deprived meal in the Septic group was 0.03+/-0.01 g, that of the Control group was 1.27+/-0.14 g; P = 0.0001), while Control rats demonstrated anticipated changes in neurotransmitters in response to eating. We conclude that the onset of anorexia in septic rats is associated with a reduction in VMN dopamine.

Animals↗
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

From food to nutritional support to specific nutraceuticals: a journey across time in the treatment of disease.

Hospitalized patients who are unable to eat or cannot eat enough to meet their metabolic needs are given parenteral or enteral nutritional support. This form of therapy is now also given to patients at home. Nutritional support is a recent development, prior to which the value of food was recognized for its medicinal benefits as nutraceuticals. The value of such "alternative" therapy is now being rediscovered by many patients who enhance their dietary intake with these traditional remedies. In Western culture, conventional medicine until recently has largely rejected the use of such "alternative" therapeutic intervention. Based on an increasing database, though, insight has been gained concerning the scientific validity of many previously termed established nutraceuticals. We focus here on the effects of honey, green tea, ginseng, and vitamin supplementation on the immune system. Honey has proven antimicrobial activity. Green tea enhances humoral and cell-mediated immunity while decreasing the risk of certain cancers and the risk of cardiovascular disease. Ginseng enhances production of macrophages, B and T cells, natural killer cells, and colony-forming activity of bone marrow. Vitamin supplementation is associated with increased antibody titer response to both hepatitis B and tetanus vaccines as a result of macrophage and T cell stimulation. Because of these findings, nutraceuticals are becoming more widely accepted as an adjunct to conventional therapies for enhancing general well-being.

Complementary Therapies↗
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

Feeding pattern in obese Zucker rats after dopaminergic and serotonergic LHA grafts.

To study the role of the lateral hypothalamic area (LHA) dopamine and serotonin in the regulation of feeding pattern during obesity, embryonic dopaminergic and serotonergic neurons from mesencephalon and rombencephalon of lean rats were grafted into the LHA of adult obese Zucker rats. Compared to the pregrafting period, a smaller increase in meal size occurred in both serotonin-grafted (9%) and dopamine-grafted (31%) rats vs control rats (51%). There was also a smaller decrease in meal number in both serotonin-grafted (3%) and dopamine-grafted (13%) rats vs control rats (28%). Although the changes in feeding pattern resulted in a decrease in total food intake in serotonin-grafted rats (5%) vs control rats, no differences in body weight gain were observed in grafted vs control rats for the duration of the study. Since adult obese Zucker rats are known to have an increased meal size and decreased meal number relative to lean rats, the data indicate the involvement of LHA dopamine and serotonin in the regulation of feeding pattern during obesity.

Animals↗
PubMed1999

Potential strategies for ameliorating early cancer anorexia.

BACKGROUND: Normally the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) interact to regulate food intake (FI), the product of meal number (MN) and meal size (MZ), by changes in neurotransmitters, mainly dopamine and serotonin. Change in LHA dopamine influences meal size; while in VMN, decreasing dopamine and increasing serotonin levels influence meal number. Whether this situation exists in early cancer anorexia was tested in a series of studies to examine the role of the hypothalamus in the pathogenesis of early cancer anorexia. MATERIALS AND METHODS: In experiment 1, male Fischer tumor-bearing (TB) rats and weight-matched controls had FI, MN, and MZ measured continuously via a computerized rat eater meter. At onset of anorexia, feeding patterns were measured. In experiment 2, the VMN was temporarily blocked with 0.32 microgram of colchicine in TB rats, while TB controls had an equal volume of intra-VMN saline, and changes in feeding patterns were measured. In experiment 3, changes in VMN dopamine and serotonin were measured via microdialysis at anorexia and after tumor resection. RESULTS: In experiment 1, with the onset of anorexia, food intake decreased significantly in TB rats, initially by a decrease in MN and then by a decrease in both MN and MZ. No change occurred in controls, suggesting that VMN versus LHA played a more significant role in mediation of cancer anorexia. In experiment 2, following VMN block, FI increased significantly in anorectic TB rats, achieved by an almost exclusive increase in MN with minimal change in MZ, thus supporting the role of the VMN in anorexia. In experiment 3, at the onset of anorexia, FI decreased significantly in TB rats versus controls. TB rats had a significant increase in VMN serotonin and a significant decrease in VMN dopamine. After tumor resection, food intake improved and high levels of serotonin normalized with no change in dopamine. CONCLUSION: Serotoninergic and dopaminergic systems are involved in the etiology of cancer anorexia. The changes in food intake are mediated via the VMN by a decrease in meal number.

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

Interleukin-1alpha injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and increases release of dopamine and serotonin.

A microdialysis injector probe administered IL-1alpha into ventromedial hypothalamus (VMN) and concurrently measured release of dopamine (DA), DOPAC, 5-HT, and 5-HIAA. After baseline dialyses, six rats received 2-ng IL-1alpha and six rats received vehicle (1 microl saline) into VMN. Sixty minutes later, food was provided for 40 min while VMN monoamines were measured every 20 min. Vehicle had no significant effect on monoamines, their metabolites, or food intake. Food intake was significantly lower in IL-1alpha rats vs. controls (p < 0.01). Baseline levels of VMN monoamines (pg/10 microl dialysate) in IL-1alpha and vehicle groups were similar. DA and 5-HT rose immediately on injecting IL-1alpha and remained higher (p < 0.05) than basal during the first 60 min and 40 min sampling period, respectively. Levels of 5-HIAA also increased (p < 0.01). Eating decreased VMN DA in controls, and decreased VMN DOPAC in IL-1alpha-treated rats. During eating, VMN 5-HT in control rats significantly increased while increasing VMN 5-HIAA occurred in IL-1alpha rats. Findings show that an IL-1alpha pathophysiological dose injected into the VMN was associated with anorexia and significantly increased dopaminergic and serotonergic activities and suggest that enhanced VMN DA and 5-HT activities may be part of an IL-1alpha-initiated cascade involved in IL-1alpha-associated anorexia.

Animals↗
PubMed1999

Infusion of nicotine into the LHA enhances dopamine and 5-HT release and suppresses food intake.

Nicotine administration induces hypophagia. Because of the involvement of hypothalamic neurotransmitters in food intake control, we hypothesized that increased activity of the lateral hypothalamic dopamine (LHA-DA) and/or serotonin (LHA-5-HT) may be responsible for nicotine-induced hypophagia. Either 4 mM nicotine or vehicle was administered via reverse microdialysis technique into the LHA of overnight food-deprived rats for 60 min; then food was provided for 40 min. The LHA-DA, 5-HT and their intermediate metabolites, DOPAC and 5-HIAA, were continuously measured during 20-min intervals before, during, and after nicotine administration. Continuous nicotine administration for 60 min increased LHA-DA and DOPAC concentrations during the first 40 min, and induced a long-lasting increase in LHA-5-HT release, until 120 min after the start nicotine administration, even when nicotine administration was stopped. The food intake during the 40-min refeeding period was significantly lower when rats received nicotine. Eating induced a significant and short-lasting increase in the LHA-DA and a long-lasting increase in the LHA-5-HT. These findings indicate that nicotine enhances dopaminergic and serotonergic activity in the LHA, and that the enhanced LHA-5-HT activity may contribute to nicotine-induced hypophagia.

3,4-Dihydroxyphenylacetic Acid↗
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↗
PubMed1999

Use of TPN in terminally ill cancer patients.

Total parenteral nutrition (TPN) is often used as an adjunct to cancer therapy. However, it is increasingly being used in terminally ill cancer patients without clearly defined reasons. To determine the validity of the use of TPN in terminally ill cancer patients, 26 patients with limited life expectancy due to end-stage cancer were given TPN by their physicians, and the validity of its use was evaluated using the criteria of 1) quality of life, and 2) ultimate outcome. Patients were divided into two groups according to the use of TPN. Group I = TPN as adjunct of medical therapy, n = 15 (eight male, seven female), mean age 32 y. Group II = TPN for in-hospital supportive care, n = 11 (two male, nine female), mean age 56 y. Nutritional status on admission, quality of life (assessed by extent of daily activities, pain, and ability to sustain oral intake), and ultimate treatment outcome were determined. Mean weight loss in patients in Group I was 8.6 kg, 11 patients out of 15 were malnourished; mean weight loss in patients in Group II was 21 kg, and all of the 11 patients belonging to this group were malnourished. Two patients of Group I improved their quality of life, while 6 declined and 7 died; in Group II, 3 improved their quality of life, 4 declined, and 4 died. We conclude that when TPN was given either as an adjunct to in-hospital aggressive therapy for cancer or for in-hospital supportive care, quality of life did not improve in the majority of patients; nor did it influence ultimate outcome. These objective data, thus, raise the question of the validity of the use of TPN in terminally ill cancer patients. However, barring the cost factor, it is recognized that subjective reasons for giving TPN to terminally ill cancer patients persist and include compassionate, ethical, religious, or emotional reasons.

Adult↗