A complication of long-term brain microdialysis.
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Animals↗
Biomedical subjects
M M Meguid
Publications and source records attributed to M M Meguid.
Hypophysial and meningeal melanocytes in the Zucker rat.
Melanocytes have not been described in the pituitary of mammals or in the meninges of the rat. In this paper, we report the presence of the cluster of melanocytes in the intermediate lobe of the pituitary and around the median eminence of the hypothalamus forming an 'infundibulo-hypophysial circle', and also describe the characteristics of meningeal melanocytes in Zucker rats. In the leptomeninges, numerous melanocytes were found on the ventrolateral surface of cerebral hemisphere in the area of the middle cerebral artery. Pigment granules were also observed in the surrounding tissue outside the melanocytes as well as incorporated in the cytoplasm of neural and epithelial cells. Electron microscopy revealed that melanosomes in hypophysial and meningeal melanocytes were in different (II-IV) stages of maturity. In the leptomeninges of Zucker rats, HMB-45 immunoreactivity was found in round non-melanosome-containing cells, while no HMB-45 reaction was found in the leptomeninges of the albino rat. We conclude that both obese and lean Zucker rats possess functionally active melanocytes in the meninges and the pituitary and transfer pigment granules to neighboring cells. The distributions of melanocytes in proximity to blood vessels in the leptomeninges and in the 'infundibulo-hypophysial circle' suggest an endocrine secretory function.
Animals↗
Use of orchiectomy and testosterone replacement to explore meal number-to-meal size relationship in male rats.
Because food intake is a function of meal number and meal size and because gender-related hormones are involved in feeding regulation, we explored effects of orchiectomy and testosterone replacement on the relationship between meal number and size and changes in resulting feeding patterns in adult male rats, randomized into orchiectomy and sham-operation groups. A rat eater meter measured feeding indexes for 1 wk before and 2 wk after castration and during 8 days of testosterone replacement. Orchiectomy leads to an immediate change in the meal number-to-size relationship, resulting in 1) change in pattern of feeding; 2) a significant decrease in dark-phase meal number; 3) a significant increase in dark-phase meal size, but insufficient to offset decrease in meal number, so total food intake significantly decreased during dark phase; 4) no significant change in light-phase meal number; and 5) an increase in meal size leading to an increased food intake during light phase, which offset decreased food intake in dark cycle and resulted in no net significant change in food intake after orchiectomy. Testosterone replacement acutely reversed effects of orchiectomy on meal number-to-meal size relationship, restoring feeding pattern. Data suggest that androgens immediately influence the meal number-to-meal size relationship. The speed of onset seen after orchiectomy suggests that the influence of testosterone on food intake may also occur partially via a nongenomic effect.
Animals↗
Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats.
With progression of tumor growth, rats demonstrate anorexia and reduced food intake, a function of meal number and meal size. Tumor necrosis factor-alpha (TNF-alpha), a recognized anorectic agent, reacts with two different receptors (type I: 55 kDa; type II: 75 kDa). We used a dimeric, pegylated 55-kDa TNF receptor construct to test its effects on food intake, meal number, and meal size, which were continuously measured with a rat eater meter in 16 Fischer 344 male rats injected with 10(6) viable methylcholanthrene cells. When anorexia developed, rats received a subcutaneous injection of either 0.25 mg/kg body wt of soluble TNF receptor construct (study) or vehicle (tumor-bearing control). Before TNF inhibitor injection, no differences were observed in food intake, meal number, or meal size between the two groups. After the TNF inhibitor injection, study vs. control rats significantly improved food intake as a result of an increase in meal number and meal size. Rats also showed a significant improvement in body weight. These data suggest that TNF-alpha, in addition to other cytokines, contributes to the anorexia of tumor growth, probably mediated via the hypothalamus.
Animals↗
Nicotine's effect on hypothalamic neurotransmitters and appetite regulation.
BACKGROUND: Tobacco smoking reduces appetite and body weight. Cessation of smoking leads to hyperphagia and weight gain. Food intake is a function of meal number (MN) and meal size (MZ) (i.e., Food intake = MN x MZ). The effect of nicotine on these feeding components and their relationships to dopamine and serotonin in the lateral hypothalamic area (LHA) were determined. METHODS: In Fischer-344 rats the effect of 7 days of systemic nicotine infusion on the feeding patterns was measured by rat eater meter and changes in serotonin (5HT) and dopamine (DA) in the LHA were measured by in vivo microdialysis. RESULTS: Nicotine infusion caused hypophagia through a significant decrease in MN with a smaller decrease in MZ, resulting in a body weight reduction. 5HT and DA concomitantly increased in LHA. Stopping nicotine resulted in hyperphagia by a significant increase in MZ. Body weight normalized. 5HT and DA in LHA decreased after nicotine was stopped. CONCLUSION: Nicotine's hypophagic effect was associated with increased 5HT and DA in LHA, whereas hyperphagia after nicotine cessation was accompanied by decreased concentrations of the neurotransmitters. These findings suggest that nicotine affects appetite regulation, in part by modulation of LHA-DA and 5HT.
Animals↗
The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.
Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.
Adult↗
Influence of systemic arginine-lysine on immune organ function: an electrophysiological study.
To test our hypothesis that arginine (Arg) and lysine (Lys) enhance immune activities via neuronal control of the thymus and the spleen, a jugular vein was cannulated for amino acid administration in male Wistar rats (approximately 300 g). In one group (n = 5), an efferent nerve filament of the vagal thymus was isolated. In another group (n = 5), splenic nerve efferents were isolated. Efferent firing rates were recorded before and for 60-90 minutes after 10 mM Arg-Lys in 0.5 ml saline intravenously (i.v.). Differences in firing rates were evaluated using analysis of variance (ANOVA) and t-test. I.v. Arg-Lys increased vagal efferent firing rate to the thymus; enhancing thymic lymphocyte release. I.v. Arg-Lys decreased firing rate in splenic efferents; enhancing natural killer (NK) cell activity. Therefore, Arg-Lys are detected by hepatoportal sensors, stimulating hepatic vagal afferents to the hypothalamus, with the efferent neuronal impulses from the hypothalamus modulating immune function in thymus and spleen, thereby demonstrating the mechanism of Arg and Lys immune enhancing activity.
Animals↗
Estrogen receptor expression in benign breast epithelium and breast cancer risk.
BACKGROUND: Estrogen exposure is a major risk factor for breast cancer. Increased estrogen responsiveness of breast epithelium may enhance this effect. We examined the relationship between breast cancer diagnosis and 1) the presence and absence of estrogen receptor expression in benign breast epithelium, 2) the level of expression and 3) its variation during the menstrual cycle, and 4) other established risk factors. e.g., age, age at menarche, parity, and family history. METHODS: We measured estrogen receptor expression (as % of positive cells) by immunohistochemistry in normal breast epithelium from 376 women undergoing diagnostic or therapeutic breast surgery. Data on established risk factors were collected prior to surgery and those on menstrual cycle dates at the time of surgery. Logistic regression was used to assess risks (odds ratios [ORs]). RESULTS: The crude OR for breast cancer in women with estrogen receptor-positive breast epithelium versus those without was 3.16 (95% confidence interval [CI] = 1.89-5.28), with an OR of 2.49 (95% CI = 1.25-4.96) for premenopausal and an OR of 3.32 (95% CI = 1.43-7.68) for postmenopausal women. The ORs remained high and statistically significant after controlling for age and other breast cancer risk factors. The level of estrogen receptor expression was higher in patients with breast cancer than in control subjects and it was related to breast cancer risk in postmenopausal women (P trend <.005). Expression declined as expected in premenopausal control subjects as the menstrual cycle progressed but rose in breast cancer patients (P trend <.015). CONCLUSIONS: The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.
Adult↗
Food intake equals meal size times mean number.
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Animals↗
Ventromedial nucleus of hypothalamus is related to the development of cancer-induced anorexia: in vivo microdialysis study.
UNLABELLED: Based on reports that increased hypothalamic ventromedial nucleus (VMN)-serotonin (5-HT) is associated with cancer anorexia and recent findings in our laboratory that low levels of dopamine (DA) in the VMN are associated with prolonged inter meal intervals thus decreased food intake, and reports that setting up satiation is concomitant with descending levels of DA in the rostromedial hypothalamus, we hypothesized that an elevated 5-HT to low DA ratio in the VMN modulates food intake in cancer anorexia. METHODS: In Expt 1: A microdialysis cannula guide was placed stereotactically into the VMN of methylcholanthrene (MCA) sarcoma tumor-bearing (TB) Fischer rats and in non-tumor-bearing (NTB) and pair-fed (PF) controls. When TB rats manifested anorexia by a decrease in food intake, VMN-5-HT, its metabolite 5-hydroxyindolacetic acid (5-HIAA), and DA with its metabolite 3,4,-dihydroxyphenylacetic acid (DOPAC) were measured by in vivo microdialysis using HPLC during baseline, in response to food, and after feeding. In Expt 2: TB rats had tumor removed and VMN microdialysis performed 7 days later. RESULTS: Increased 5-HT release and turnover, and significantly reduced DA release with increased DOPAC occurred in TB vs NTB or PF rats. When food was offered, intake in TB rats was significantly lower than in NTB control rats. During eating, VMN-5-HT rose and peaked significantly earlier in TB vs NTB rats, while DA release was significantly reduced. With eating, the 5-HT and DA metabolism became reduced in all rats. Seven days after surgical removal of the tumor, 24 h food intake had increased to the level of controls; and when food was offered during microdialysis, intake in TB rats increased (ns relative to control), but was not yet normal. VMN microdialysis showed that 5-HT was normal at baseline, as well as during and after eating, while DA remained depressed. The metabolic turnover of 5-HT and DA was significantly lower in TB-r and PF vs NTB rats. We conclude that increased 5-HT/DA ratio is related to the development of cancer-induced anorexia.
3,4-Dihydroxyphenylacetic Acid↗
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↗
Eating-associated VMN-dopamine levels of rats: comparison of oral and intragastric feeding.
Eating is associated with persistently low dopamine (DA) concentration in the ventromedial hypothalamic nucleus (VMN), postulated to influence postprandial satiety. Whether pregastric factors contribute to eating-associated low VMN-DA was examined. VMN-DA levels were continuously measured in awake rats, food-deprived for 24 h, and either subsequently allowed to eat solid chow freely available for 20 min, an oral liquid diet, or an isovolemic isocaloric liquid diet infused intragastrically to bypass the oropharynx. Eating either solid chow or a liquid diet was associated with an immediate decrease in VMN-DA concentration. The lower VMN-DA concentration lasted longer after solid chow was consumed than following consumption of the liquid diet. When the oropharynx was bypassed no significant change in VMN-DA concentration was observed either during or after the liquid diet was infused. Results suggest that pregastric oropharyngeal factors contribute to eating-associated low VMN-DA concentration.
Administration, Oral↗
Creation of a neoabdominal wall to facilitate emergency placement of a terminal ileostomy in a morbidly obese patient.
Morbid obesity of the abdominal area creates difficulty with creation of a Brooke ileostomy because of thickened, foreshortened mesentery of the terminal ileum, limitation to mobilization, and thickness of the abdominal wall through which the terminal ileum must be placed in the stoma, causing undue tension on the vasculature with a higher frequency of retraction and necrosis. Such a problem may be ameliorated by performing a subcutaneous lipectomy about the stoma and creating a thinned neoabdominal wall to facilitate the creation of a temporary Brooke stoma. Despite initial difficulty with stoma appliances, this operative technique in selected obese patients outweighs the limited complications that may be encountered.
Abdominal Muscles↗
Meal-induced changes in hepatic glycogen of fasted rats.
Hepatic metabolism of glucose and other nutrients influences feeding behavior. The present study was conducted to confirm prandial decreases in hepatic glycogen concentrations following a short-term fast. Male Sprague-Dawley rats were fasted 6-12 h during the light phase before having access to chow for one or two 20-min meals at the beginning of the dark phase. Plasma glucose and insulin concentrations in hepatic and portal venous blood and hepatic glycogen concentrations prior to and at the end of each meal were compared. Glucose concentration in the hepatic vein was greater than that in the portal vein prior to the meals but not at the end of the meal. Insulin levels were higher in the portal vein than the hepatic vein pre- and postprandially. Hepatic glycogen concentrations increased after each meal in younger (2-month-old) rats but not older (6-month-old) rats. Fasting levels of hepatic glycogen were lower in the younger rats than the older rats; however, the increase in hepatic glycogen was not due to differences in baseline glycogen concentrations at the start of the meal. The reported prandial decreases in hepatic glycogen of fasted rats were not apparent in this study. Because of the difference between 2- and 6-month-old rats in periprandial hepatic glycogen metabolism after a short-term fast, the age of the animal needs to be considered if the dynamics of liver glycogen metabolism are to be incorporated into a model of food intake regulation.
Age Factors↗
Bilateral hypothalamic dopamine infusion in male Zucker rat suppresses feeding due to reduced meal size.
Lateral hypothalamic area dopamine activity (LHA-DA) appears to play a contributory role in regulating food intake, in particular, meal size. In this study we examined our hypothesis that bilateral LHA-DA injection induced depression of food intake via reduced meal size. Dopamine (11 mg/ml) or vehicle was infused into bilateral LHA at 0.5 microliter/h via two osmotic minipumps in six study or six control obese male Zucker rats for 13 days, respectively. Meal size, meal number, as well as food intake were continuously measured before, during, and after dopamine infusion. Intra-LHA-DA infusion significantly depressed food intake. The decreased food intake was solely caused by a significant and profound reduction in meal size. There was a modest compensatory rise in meal number that gradually increased food intake so that it reached control level on 10th dopamine infusion day. However, feeding pattern did not normalize until dopamine infusion ceased. The findings support our hypothesis that LHA-DA may participate in regulating meal size. Data also demonstrate that meal size and meal number are regulated in a reciprocal and independent manner to compensate for each other.
Animals↗
Venocutaneous fistula: a central venous catheter--associated complication.
Central venous catheter placement for parenteral feeding, whether short-term as in acute hospital care or long-term as in home total parenteral nutrition (TPN), is a well-established intervention in the patient who cannot eat. Access to the central venous system in the majority of the cases is gained by insertion of the catheter into either the subclavian or jugular vein. Associated with central venous catheters is the possible development of mechanical and septic complications, the incidence of which depends upon the skill, experience, and commitment of both the patient and the nutrition support team. A case report is presented in which a woman developed a venocutaneous fistula due to a chronic indwelling right internal jugular central catheter placed for long-term home nutritional support. The patient's medical history, management of her catheter, and proposed etiology for this problem are discussed, and complications of central access and TPN usage are addressed.
Adult↗
Meal size and number: relationship to dopamine levels in the ventromedial hypothalamic nucleus.
Evidence shows a reciprocal relationship exists between the lateral hypothalamic area (LHA) and the ventromedial hypothalamic nucleus (VMN) in food intake regulation. Since a direct correlation between meal size and LHA-dopamine in Fischer rats was previously reported, we tested the hypothesis that an inverse association may exist between meal size and VMN-dopamine response. This was studied in awake 24-h food-deprived rats who were then allowed to eat freely for 20 min while the VMN-dopamine response was measured by microdialysis every 20 min for 2 h. In a second experiment, only one-half the amount freely eaten was provided during microdialysis. The following were observed. 1) Dopamine concentrations in VMN decreased during eating. 2) The degree and duration of decrease after the meal corresponded to the size of the meal. 3) When the decreased postmeal VMN-dopamine level had returned to baseline and food was available, rats ate once more. The findings show that, in normal rats, eating was associated with decreased dopamine levels in the VMN and was followed by a lag time during which no additional eating occurred. VMN dopamine levels thereby contribute to determining the duration of the intermeal interval and hence, by inference, the meal number.
Animals↗