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Biomedical subjects

M M Meguid

Publications and source records attributed to M M Meguid.

At least 73 records · Page 4Linked to original sources
PubMed1997

Drug-nutrient interactions in enteral feeding: a primary care focus.

Drug and nutrient interactions are complex and can take many forms, including malabsorption of either the drug or the nutrient component. Some drugs can stimulate or suppress appetite, whereas others can cause nausea and vomiting resulting in inadequate nutritional intake. Absorption of drugs is a complex process that can be affected by the physical characteristics of the gastrointestinal tract (GIT) as well. Depending on the physical properties of a drug, it may be absorbed in a limited area of the GIT or more diffusely along much of the entire length. Many diseases and conditions are also known to affect the GIT either directly or indirectly. Dietary factors also need to be considered when the "food" is an enteral formula. The widespread use of enteral tubes requires that consideration be given to patients receiving both enteral feedings and medication concurrently. The location of a tube in the gastrointestinal tract, as well as the problems involved in crushing and administering solid dosage forms, creates a unique set of problems.

Biological Availability↗
PubMed1996

Mechanism of early tumor anorexia.

Whether in tumor-bearing rats a temporal relationship exists between an increase in plasma free tryptophan (FTRP), an increase in brain serotonin (5-HT), and onset of anorexia was studied. Rats were assigned to three groups: tumor-bearing (TB), pair fed (PF), and controls. Food intake was recorded daily. In TB rats anorexia developed on Day 18 and thereafter food intake decreased progressively until end of study. After tumor inoculation, tumor became palpable on Day 10 and continued to grow exponentially until end of study. Rats were killed on Days 6, 10, 16, 18, 22, and 26 to determine plasma FTRP, FTRP/LNAA, and brain 5HT and compared to PF and controls. On Day 6, before tumors became detectable, FTRP and FTRP/LNAA were increased (P < 0.05) in TB rats vs controls. Both continued to increase so that by Day 18 when food intake had started to decrease (P < 0.05), brain 5-HT increased and correlated with the onset of anorexia (R2 = 0.6, P < 0.05). Increases in plasma FTRP the precursor to brain 5-HT occurred in TB rats before physical appearance of tumor and increased until an increase in brain 5-HT occurred, leading to anorexia.

Amino Acids↗
PubMed1996

Increased food intake and body weight gain after lateral hypothalamic dopaminergic cell implantation.

To examine our hypothesis that dopamine activity in the lateral hypothalamic area (LHA) may play a role in enhancing the process of eating, a fetal cell suspension of predominantly dopaminergic cells was bilaterally transplanted into the LHA of study rats via direct injection; controls had carrier medium injection. Thereafter, mean daily food intake was 1 g per day greater in dopaminergic cell transplanted rats vs. controls for each day of the 10-week observation period. This resulted in a significantly greater cumulative body weight gain in study rats vs. controls (386 +/- 5.1 g vs. 354 +/- 3.8 g, respectively). On sacrifice at the end of the study, transplanted cells in the LHA were viable. Our data suggest that bilateral LHA dopaminergic cell transplant which presumably resulted in chronically and persistently enhanced dopaminergic activity in the LHA is associated with overeating and consequently, an excess weight gain.

Animals↗
PubMed1996

Intravenous nucleosides and a nucleotide promote healing of small bowel ulcers in experimental enterocolitis.

Our aim was to evaluate the possible beneficial effect of intravenous nucleosides and a nucleotide in healing small bowel ulceration in a rat model of enterocolitis. Fourteen Lewis female rats were randomized into total parenteral nutrition (TPN, N = 7) and TPN + nucleosides and a nucleotide (NS/NT, N = 7) groups. After adaptation, two doses of indomethacin (7.5 mg/kg) were administered subcutaneously 24 hr apart to each animal in both groups. Concomitant with the first dose of indomethacin, TPN or TPN + NS/NT were infused for four days. The TPN and TPN + NS/NT were isocaloric and isonitrogenous. At the end of four days, total ulcer length in the entire small bowel was measured. The mucosa surrounding ulcers was studied by optical microscopy. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA). Ileal crypt and villus lengths were measured with an eyepiece micrometer, crypt-villus ratios were calculated, and crypt mitotic index and percentage of PCNA-labeled cells determined to assess cellular proliferation. Total ulcer length decreased significantly in the TPN + NS/NT group compared to the TPN group (42 vs 76 mm). In the TPN + NS/NT versus TPN group, the ileal mucosa surrounding ulcers showed significantly greater crypt length (21%) and there was increased crypt-villus ratio (0.53 vs 0.39), crypt mitotic index (1.2 vs 0.9), and PCNA labeling (43% vs 30%). We conclude that in rats with indomethacin-induced enterocolitis, administration of TPN + NS/NT for four days resulted in significant healing of small bowel ulcers, as indicated by decreased ulcer length. This effect of NS/NT appears to relate, in part, to increased cell proliferation, evidenced by increased crypt length, crypt-villus ratio, mitotic index, and PCNA labeling.

Animals↗
PubMed1996

Carnitine supplementation accelerates normalization of food intake depressed during TPN.

When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3-4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3-4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls (n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group (n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.

Animals↗
PubMed1996

Studies on the regulation of food intake using rat total parenteral nutrition as a model.

Total parenteral nutrition (TPN) is essential for maintaining the nutritional status of patients who are unable to eat sufficiently to meet their metabolic needs. However, TPN suppresses appetite and ultimately diminishes food intake. Theories concerning the role(s) of peripheral metabolites as signals, acting via the liver and the hypothalamus, for the metabolic control of food intake, have been put forward to explain the anorectic effect of TPN. In addition, it is postulated that changes in peripheral metabolites during TPN may be translated into changes in the levels of brain neurotransmitters known to decrease food intake. This review summarizes studies concerning the effect of TPN on food intake. These studies have involved: (1) characterizing the changes in feeding activity due to TPN; (2) investigating the involvement of the central nervous system; and (3) investigating the role of the periphery and its metabolites in the regulation of food intake during TPN. Some insight into the mechanism of action of TPN on food intake is provided.

Animals↗
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

Cancer anorexia: new pathogenic and therapeutic insights.

During tumor growth, anorexia and reduced food intake markedly contribute to the development of malnutrition, thus worsening overall patients' survival. A better understanding of the pathophysiology of eating behavior may lead to new and more effective therapies, aiming at counteracting the detrimental effects of anorexia and reduced food intake on nutritional status and survival in cancer patients. Brain tryptophan and serotonin concentrations seem to play a pivotal role in the regulation of eating behavior. Increased brain serotonin activity is indeed associated with a reduction of food intake. It has been recently hypothesized that increased availability of tryptophan to the brain and the consequent increased serotonin activity may represent the pathogenic mechanism for cancer-associated anorexia. According to this hypothesis, the modulation of brain serotonin activity may result in an improvement of anorexia. Reducing brain tryptophan availability represents a possible mechanism to restore brain serotonin activity to normal. There is evidence that the oral administration of neutral amino acids competing with tryptophan for brain entry results in a significant improvement of cancer anorexia. The same treatment may also be effective in improving secondary anorexia, which is associated with other chronic illnesses, including renal and liver failure, sepsis, and so forth, sharing a similar pathogenic mechanism.

Animals↗
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

Nutritional management of patients with gastrointestinal fistulas.

Nutritional support plays a key and integral role in the management of patients with gastrointestinal fistulas. It needs to be instituted early to minimize erosion of body cell mass, to prevent further physiologic deterioration of the patient, and to initiate repletion in an otherwise malnourished patient. Furthermore, it allows for rest of the gastrointestinal tract and facilitates healing of the fistula.

Anthropometry↗
PubMed1996

Factors influencing outcome in patients with gastrointestinal fistula.

The analysis of the prognostic factors in patients with gastrointestinal fistula requires an assessment of the quantitative and qualitative characteristics of the study population. General patient characteristics such as age, presence and degree of malnutrition, levels of plasma proteins, diagnosis of cancer or inflammatory bowel disease, or systemic sepsis must be considered, as well as local fistula characteristics. Besides the local anatomic characteristics of the fistulous tract, other factors such as fistula output, organ of origin, cause, and duration of the fistula must be considered in the assessment of a fistula patient. It is recognized, however, that it is very difficult to conclude that the presence of a single prognostic factor increases the risk in patients as complex and heterogeneous as those with digestive fistulas. It remains to be shown whether the combination of several predictive factors may enhance the chances of accurately predicting fistula closure and mortality in digestive fistulas.

Fistula↗
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

Nutritional issues in cancer management.

The objective of this article was to investigate the relationship between nutrition and cancer, as it relates to the initiation, promotion, and treatment of tumor growth. English-language studies published in the last 25 years were retrieved using MEDLINE, bibliographies, and consultation with experts. MEDLINE search terms included "cancer", "malnutrition," and "nutritional support." In vitro and in vivo controlled studies addressing the impact of nutritional factors on cancer prevention and treatment were selected. Approximately 30% of cancers in the Western countries are diet-related. The presence of malignancy affects patients' nutritional status negatively, leading to increased morbidity and mortality. Standard nutritional support (both enteral and parenteral) is not always effective in significantly improving outcome in malnourished cancer patients, due to characteristic changes in host metabolism. Preliminary studies suggest that newer nutritional-pharmacologic agents may be beneficial in counteracting the derangement of host metabolism, and consequently in ameliorating cancer patients' nutritional status and outcome of malnourishment. This review suggests that dietary manipulations and nutritional-pharmacologic therapy might be highly effective adjuncts in controlling the symptoms of patients with neoplastic disease.

Cachexia↗
PubMed1996

Eating-related increase of dopamine concentration in the LHA with oronasal stimulation.

Previously, we showed that eating was associated with an increase in lateral hypothalamic area dopamine (LHA-DA) release, which returns to previous level when eating stops. We therefore hypothesize that LHA-DA release may be primarily contributed to by oronasal stimulation. To test our hypothesis, microdialysis was used to compare LHA-DA release during oral and intragastric feeding. A gastrostomy tube was inserted in 12 rats. After recovery from surgery, in vivo microdialysis was performed. Six rats were allowed to drink a liquid diet, whereas in another six rats the same liquid diet was infused at paired doses (volume = 4.8 +/- 0.6 ml; time = 5-10 min) through the gastrostomy tube into the stomach. Oral feeding increased baseline LHA-DA from 10.6 +/- 0.2 to 14.0 +/- 0.8 pg/10 microliters dialysate (P < 0.01) within 20 min. No significant change in measured LHA-DA occurred during intragastric feeding [baseline: 10.5 +/- 0.3 pg/10 microliters; postintragastric: 10.2 +/- 0.3 pg/10 microliters (P < 0.01 vs. oral feeding)], indicating that LHA-DA release occurs with oronasal stimulation.

Administration, Oral↗