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Biomedical subjects

M M Meguid

Publications and source records attributed to M M Meguid.

At least 109 records · Page 6Linked to original sources

Metabolic influences on satiety in rats receiving parenteral nutrition.

Food intake is reduced during parenteral nutrition (PN) proportionally to the amount of calories or composition of the solution infused. The relative importance of infused glucose and lipid, 50 and 30% of PN kilocalories, respectively, in reducing food intake during PN was examined. Glycolysis, fatty acid oxidation, or both were acutely disrupted with 2-deoxy-D-glucose (2-DG) and mercaptoacetate (MA). Rats receiving intravenous infusions of saline or a PN solution providing 100% of total daily calories (PN-100) received a single intraperitoneal injection of saline, 2-DG, and/or MA during the early light phase. 2-DG (1.4 or 2.2 mmol/kg) did not initiate feeding in PN-100 rats, although hyperglycemia was evident in all rats 1 h after 2-DG. Food intake of PN-100 rats after MA (0.4 mmol/kg) was approximately 50% that of control rats. When 2-DG (1.4 mmol/kg) and MA (0.4 mmol/kg) were administered concomitantly, PN-100 and control rats consumed the same amount of food. During PN-100, rats appeared to be more sensitive to losing metabolic energy derived from lipid than from glucose.

Animals↗

Hepatic vagotomy effects on metabolic challenges during parenteral nutrition in rats.

During parenteral nutrition (PN) glucoprivic-induced feeding appeared to be neutralized by the oxidation of infused fatty acids. With the use of a latin-square design, the feeding response to 2-deoxy-D-glucose (2-DG) and/or 2-mercaptoacetate (MA) was evaluated in male Sprague-Dawley rats with hepatic branch vagotomy (HV) or sham operations (SO). Rats received continuous infusions of 0.9% saline or PN providing 100% of daily caloric needs (PN-100) for four consecutive days. During PN-100, food intake was stimulated by 2-DG in HV rats and when fatty acid oxidation was simultaneously inhibited by MA. 2-DG-induced hyperglycemia was apparent under all conditions. Lipoprivic-induced feeding and increased plasma free fatty acid concentrations were absent in HV rats, whether MA was administered alone or with 2-DG. The feeding response to glucoprivic challenges is influenced by the relative availability of alternate energy sources. The lack of feeding response to 2-DG during PN-100 is mediated by vagal input of hepatic fatty acid oxidation status.

Animals↗

Factors influencing compensatory feeding during parenteral nutrition in rats.

During parenteral nutrition (PN) there is an incomplete compensatory decrease in oral caloric intake. The effects of two factors influencing nutrient utilization, diurnal timing of PN infusion and composition of available diet, on compensatory feeding were investigated in male rats receiving 100% of daily caloric need as PN (PN-100). Compensation for infused calories increased from 70 to 80% (P < 0.05) when the timing of infused kilocalories more closely matched diurnal pattern of oral kilocalories intake (e.g., 75% kcal daily during the dark phase, 25% during the light phase). There was a similar degree of compensation when the diet and PN-100 had the same caloric distribution (50% kcal from carbohydrate, 30% from fat, and 20% from protein). Adjusting the diurnal timing of infused calories and diet composition concurrently further increased compensation for infused calories from 70 to 90% (P < 0.05). In the rat PN-100 model, compensation for infused calories is improved by adjusting the temporal pattern of infusions and diet composition.

Adaptation, Physiological↗

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↗

Parenteral nutrients in rat suppresses hepatic vagal afferent signals from portal vein to hypothalamus.

BACKGROUND: Parenteral nutrition (PN) suppresses spontaneous food intake in rats by stimulating dopamine in lateral hypothalamic area (LHA), which is attenuated by vagotomy. Sensors for glucose and for some individual amino acids exist in hepatoportal areas sending signals via hepatic vagal afferents to LHA. Hypothesizing that the decrease in spontaneous food intake occurs because a PN amino acid solution is recognized by portal vein sensors, we measured afferent nerve discharges in hepatic vagus in response to PN. METHODS: Hepatic vagus was divided in 11 rats, and an isolated nerve filament was placed on recording electrodes. Afferent firing rate was recorded before and after injecting during 1 minute a well-balanced crystalline amino acid mixture into either the portal or peripheral vein. Isotonic glucose was used as standard solution. RESULTS: A significant decrease in hepatic vagal afferent discharge rate was recorded after both intraportal and intravenous injection of the PN amino acid mixture. The mean discharge rate was inversely related to the concentration of the solution. Successive injections produced further decreases in discharge rate, and the effect was more sustained. CONCLUSIONS: The observed decrease in discharge rates suggests that the crystalline amino acid PN solution is sensed in hepatoportal areas informing LHA via hepatic afferents. This effect may play a role in regulating food intake during PN.

Afferent Pathways↗

Current uses of total parenteral nutrition.

Total parenteral nutrition has become a well-established intervention for the following indications: to sustain life in patients with short-bowel syndrome; for perioperative use in nutritionally deprived patients; to improve quality of life for patients with inflammatory bowel diseases; to assist the healing of enterocutaneous and pancreatic fistulas; for supportive care in patients with acute pancreatitis; as an adjunct to therapy in patients with acute renal or hepatic failure; for hypermetabolic states such as sepsis, trauma, burns and acquired immunodeficiency syndrome; in neonatal and pediatric patients; in transplantation recipients, including bone marrow, renal, cardiac and liver transplants; for precoronary artery bypass graft myocardial glycogen loading; in the field of obstetrics; to enhance survival in patients with closed head injuries; to treat life-threatening anorexia nervosa; in patients with cystic fibrosis and for nutritional support in home use.

Critical Care↗

Effect of intragastric and intravenous ethanol on food intake in rats.

The effects of a continuous intragastric (via a gastrostomy) and intravenous (via an indwelling jugular catheter) infusion of 3% ethanol at 3 ml/h on food intake was examined in rats randomly assigned to a two period crossover study. The 3% ethanol solution provided 19 kcal/day, which was equivalent to about 50% of the daily caloric intake of the rats. Ethanol significantly decreased food intake irrespective of the route administered. But, reduction in food intake did not result in a calorie-to-calorie compensation. Instead, providing 50% of calories as 3% ethanol via the intragastric route led to a 16% reduction in food intake, while only a 9% reduction in food intake occurred when the 3% ethanol solution was given intravenously.

Animals↗

Olfactory bulbectomy in rats modulates feeding pattern but not total food intake.

The role of olfactory input in the regulation of food intake and feeding patterns in rats was investigated by performing bilateral olfactory bulbectomy. Compared to control rats, bulbectomized rats ate the same amounts of food, but did so via a decrease in meal size, and a doubling in meal number. Although no increase in meal duration occurred, the exploratory behavior of sniffing during meals and between meals also increased significantly. While it is not yet clear how the olfactory bulbs participate in regulating food intake configuration resulting in changed feeding patterns, their clinical role can be appreciated by observing the acute changes in feeding pattern that occur when their input to the lateral hypothalamic area is damaged experimentally.

Animals↗

Dynamics of central venous catheter-related sepsis in rats.

To determine when catheter-related sepsis clears after removal of an infected central venous catheter (CVC) and when a new sterile CVC can be inserted without risk of recolonization, a catheter infected with 10(5) CFU of Staphylococcus epidermidis per ml was inserted into 40 Fischer 344 rats. Five control rats had sterile catheters. Insertion of an infected CVC was followed by a significant rise in leukocytes after 4 days and the presence of S. epidermidis in lungs, livers, spleens, kidneys, and the catheter tip, as examined by bacteriological assay. After the infected catheter was removed, the rat recovered from the induced catheter-related sepsis within 12 h. When a new sterile CVC was inserted into the femoral vein, the leukocyte count remained normal, and all catheter tips and tissue cultures were sterile 4 days later.

Animals↗

Parenteral nutrition, brain glycogen, and food intake.

To determine whether brain glycogen concentrations change during parenteral nutrition, Fischer 344 rats with jugular vein catheters received 0.9 N saline or parenteral nutrition providing 100% of daily calories (PN-100). Rats were killed after 4 days of PN-100 and serially after PN-100 was stopped. Food intake decreased during PN-100 to approximately 15% of control, but total kilocalories eaten and infused over the 4-day PN-100 period was approximately 130% of control. Food intake of PN-100 rats remained low for 3-4 days post-PN-100. At the end of the 4-day PN-100 period, plasma glucose and insulin (P = 0.01) and whole brain glycogen (P < 0.005) were higher than but similar to control within 24 h of PN-100 being stopped. When PN-100 rats were not allowed to eat during the infusion period, plasma glucose was lower, plasma insulin higher, and brain glycogen content the same as in control rats after 4 days of PN-100. The increased brain glycogen was the likely consequence of the hyperglycemia and hyperinsulinemia during PN-100 and was not causally associated with the reduced food intake either during or immediately after PN-100.

Animals↗

Lateral hypothalamic dopaminergic neural activity in response to total parenteral nutrition.

BACKGROUND: The lateral hypothalamic dopaminergic neurons dominate modulation of food intake. Changes in lateral hypothalamic synaptic dopaminergic release before and during total parenteral nutrition (TPN) and its components were measured in vivo with microdialysis probes. METHODS: Rats had an intracerebral guide cannula and an internal jugular catheter placed. Ten days after recovery, rats were fasted for 24 hours. A 2 mm microdialysis probe was inserted into the lateral hypothalamus neurons via the guide cannula. Dopamine level was measured by high-performance liquid chromatography in three 60-minute baseline dialysis samples. TPN, glucose, fat, or amino acid was then infused via the internal jugular catheter, and dopamine level was measured in three more 60-minute dialysate samples. Single nutrients were infused for 24 hours, and dopamine was measured during the 3 hours after the infusions were stopped. Data were analyzed by paired t test (mean +/- standard error) and represented percentage change from baseline. RESULTS: Dopamine levels rose significantly (p < 0.05) and remained so during infusions in TPN (26% +/- 3%), glucose (26.5% +/- 4.6%), fat (36.2% +/- 6.7%), and amino acids (9.6% +/- 4.2%). After infusions were stopped, dopamine levels decreased to -35.4% +/- 1.5% in glucose but remained unchanged with fat and amino acids. CONCLUSIONS: Increase in lateral hypothalamic dopamine level occurs with TPN and its components, and changes persist temporarily after stopping the infusions, explaining in part the slow recovery of food intake after TPN is stopped.

Animals↗

Amino acid profiles correlate diagnostically with organ site in three kinds of malignant tumors.

The hypothesis that tumors arising in a particular organ site impose a characteristic plasma free amino acid (PFAA) pattern was tested by analyzing PFAA in fasting venous blood of preoperative patients with breast cancer, gastrointestinal tract cancer, and head and neck cancer. Healthy volunteers served as control subjects. Levels of 28 PFAA were determined in blood samples using an amino acid analyzer, and the data were compared using discriminant analysis and chi-square testing. Compared with control subjects, the concentrations of seven amino acids (glutamine, threonine, histidine, cysteine, alanine, arginine, and ornithine) in patients with tumors correlated closely with the known diagnoses. By means of discriminant analysis, these seven amino acids had the highest correlation with the specific diagnoses, indicating that PFAA profiles correlate diagnostically with the organ-site origin of three different kinds of malignant tumors.

Adenocarcinoma↗

Influence of anterior subdiaphragmatic vagotomy and TPN on rat feeding behavior.

Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and of longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake.

Afferent Pathways↗

Nocturnal cyclic versus continuous total parenteral nutrition: food intake and feeding pattern in rats.

Total parenteral nutrition (TPN), providing the equivalent of 100% of mean daily oral intake for 24 hours, depressed spontaneous food intake (SFI) in rats by a mean greater than 80%. Whether TPN had the same effect on SFI when given either in 12-hour cycles (Cyclic-TPN) or in 24 hours (Continuous-TPN) for 8 days was tested in 16 rats with jugular catheters, placed in metabolic cages modified with an Automated Computerized Rat Eater Meter. This continuously measures food intake and its dependent indexes: meal number, meal size, meal duration, meal sniffs and intermeal sniffs. Both rat groups ate the same amounts of chow before TPN. On starting TPN, food intake decreased by greater than 80% in Cyclic-TPN and greater than 50% in Continuous-TPN during each first infusion period. A nadir in food intake was reached in 48 hours with Cyclic-TPN and in 72 hours with Continuous-TPN. Thereafter, there was no food intake during the 12 hours of Cyclic-TPN, with minimal food intake during the intervening 12 hours of non-TPN normal saline infusion period. In both forms of TPN infusion, a reduction in food intake was achieved by a reduction in meal number and size, and thus in meal duration. Feeding-related sniffing activity was decreased by similar amounts with Cyclic- or Continuous-TPN. Cyclic-TPN for 12 hours had no advantage over Continuous-TPN, in that there was no compensatory enhancement of food intake and meal-related behavior during the cyclic non-TPN normal saline period.

Animals↗

The comparative effects of abrupt vs. stepwise discontinuation of TPN in rats.

The comparative effects of discontinuing total parenteral nutrition (TPN: caloric ratio of glucose:fat:amino acid = 50:30:20) abruptly or in a stepwise manner on spontaneous food intake were investigated in two studies. Study 1: In 16 rats, TPN was given for 4 days, then stopped abruptly in eight rats. In the other eight rats, TPN was tapered; they received TPN at 75%, 50%, and 25% of their mean daily energy requirements per day for 3 consecutive days, and then switched to normal saline. Total parenteral nutrition induced a significant 60% reduction in spontaneous food intake (SFI) in both groups during the first TPN day. After 4 days of TPN, an 80% decrease in SFI had occurred in both groups. Resumption of SFI was significantly sooner in the abruptly-stopping group than in the stepwise-stopping group. But, in the latter group, there was a significantly greater cumulative caloric intake during the entire study. Study 2: In 32 rats, TPN providing either 100%, 50%, or 25% of their mean daily caloric requirements was given to three groups each of eight rats, for 3 days, then abruptly changed to normal saline; control rats received normal saline throughout. The TPN-induced decrease in SFI was proportional to the caloric density of the solution infused. Three days of 100%, 50%, or 25% TPN infusion led to an approximate 85%, 60%, or 35% decrease in SFI, respectively. Spontaneous food intake recovery was independent of the caloric density of TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dynamics of oral intake resumption after general anesthesia and operation in rats.

The influence of general anesthesia and operation on dynamics of postoperative food intake resumption was investigated in eight rats. A laparotomy was performed on each rat under anesthesia induced by intraperitoneally injected chloral hydrate. Spontaneous food intake and feeding indexes were continuously measured using an Automated Computerized Rat Eater Meter (ACREM) before and after operation. Although spontaneous food intake and all feeding indexes were depressed immediately following anesthesia and operation, each feeding index was depressed to a greater degree during the dark vs. the light cycle. Initially, rats fully capable of eating ate fewer, smaller, and shorter meals. The return to normal of each feeding index differed temporally. Thus, although meal number normalized by the third postoperative day, meal size by the sixth postoperative day, and meal duration by the fourth postoperative day, normalization of meal number during the light cycle occurred sooner than during the dark cycle, while the converse occurred with meal size and meal duration.

Anesthesia, General↗

Muscle performance and adenine-nucleotides status in MCA-sarcoma tumor-bearing rats.

The reduction in DNA, RNA, amino acid, and total protein in muscle tissue of tumor-bearing rats may influence muscle function. The effects of MCA-sarcoma tumor burden on muscle performance and adenine nucleotides was evaluated in three fiber types of skeletal muscle. Twenty-one days after MCA-sarcoma tumor inoculation, the gastrocnemius-soleus muscle group of Fischer 344 rats was stimulated using an in situ preparation; tetanic stimulation for 10 min at 7.5, 15, or 30 tetani per min (TPM) or 60 TPM for 5 min (n = 6 control and six tumor-bearing rats/group). ATP, ADP, AMP, IMP, phosphocreatine, and creatine content in white and red gastrocnemius muscle and soleus muscle was measured. There were no differences among controls and tumor-bearing rats in force output; however, ATP content in the soleus muscle of tumor-bearing rats was significantly reduced after 30 TPM for 10 min or 60 TPM for 5 min. The performance of skeletal muscle, over a wide range of stimulation frequency, in tumor-bearing rats does not appear to be influenced by changes in adenine nucleotide content.

Adenine Nucleotides↗

High frequency-low morbidity mechanical complications of tube feeding: a prospective study.

Because of preferential use of the enteral route for nutritional support, a prospective study of mechanical complications was done in 109 consecutive patients. One hundred seventy-two nasogastric tubes were placed in 60 patients, 42 esophagostomies in 28 patients, 32 gastrostomies in 22 patients and 9 jejunostomies in 8 patients. Data show that the use of enteral feeding tubes is not without complications. The complications fell into two major categories. There were 15 low frequency mechanical complications, of which four (2 carotid artery blowouts, 1 gastrointestinal perforation, and 1 aspiration) were of high morbidity and 11 of low morbidity. There were 132 high frequency-low morbidity complications with the use of 255 tubes. These consisted mainly of unplanned and untimely removal of feeding tubes with interruption of feedings and necessitating tube replacement. Data indicate that the main problems related to the use of enteral nutrition are not the dramatic complications which create notoriety but those related to the ordinary mechanical complications occurring daily and which command little attention because of their low mortality. These can assume importance because of their high frequency and as such are characterized as high frequency-low morbidity complications.

Journal Article↗