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Biomedical subjects

K N Jeejeebhoy

Publications and source records attributed to K N Jeejeebhoy.

At least 19 recordsLinked to original sources

Nutritional and metabolic effects of the endotoxin bacterial lipopolysaccharide in orally and parenterally fed rats.

BACKGROUND: Animals treated with tumor necrosis factor alpha (TNF-alpha) developed severe metabolic abnormalities despite receiving sufficient protein and energy by total parenteral nutrition (TPN). OBJECTIVE: We sought to investigate the nutritional and metabolic effects of bacterial lipopolysaccharide (LPS) in rats. DESIGN: Rats were randomly allocated to 5 groups: oral nutrition (ON control; n = 7), TPN control (n = 7), ON+LPS (n = 6), TPN+LPS (n = 9), and pair fed (PF) in relation to ON+LPS (n = 6). RESULTS: Body weight decreased significantly as diet consumption decreased in the ON+LPS and PF groups compared with the ON control group. Relative carcass weights were significantly lower in the TPN+LPS and ON+LPS groups than in their respective control groups. Diaphragm and extensor digitorum longus weights were significantly lower in the ON+LPS and PF rats, but not in the TPN+LPS rats, compared with their respective controls. Biochemical abnormalities and plasma corticosterone concentrations were greater in the TPN+LPS group than in the other groups. CONCLUSIONS: These data suggest that provision of sufficient protein and energy by TPN does not prevent general carcass wasting induced by LPS but may protect individual muscles. However, compared with an oral ad libitum diet, TPN providing sufficient protein and energy worsens the biochemical abnormalities induced by LPS. More rapid clearance of TNF-alpha and low corticosterone concentrations in weight-losing animals may help reduce the severity of the metabolic effects of LPS.

Animal Nutritional Physiological Phenomena↗

Vegetable proteins: are they nutritionally equivalent to animal protein.

On the basis of the rate of animal growth, proteins have been traditionally classed as high quality, such as egg and milk protein, or low quality such as gluten. In general, vegetable proteins are of low quality but soy protein is an exception. The paper by Capristo et al. in this issue of the journal has shown that enteral formulations consisting of soy protein are as effective nutritionally as enteral formulations containing milk protein.

Dietary Proteins↗

The role of chromium in nutrition and therapeutics and as a potential toxin.

Since the 1950s it has been known that chromium is important for the expression of glucose tolerance and that in chromium deficiency the use of glucose is impaired. Chromium has been recognized as an essential nutrient since the finding of low-molecular-weight chromium as a biological modifier of insulin action and the clinical demonstration of deficiency associated with glucose intolerance that responded to the administration of chromium. The major impediment to the use of orally administered chromium is poor absorption of trivalent chromium in its inorganic form. Trivalent chromium is more available in yeast and, more recently, as chromium picolinate for oral absorption. The widespread use of these supplements has resulted in controversy regarding chromium's role as a nutrient, its use for treatment of insulin resistance, and its potential toxicity. This report reviews the evidence for the potential toxicity of chromium supplements in contrast with its usefulness as a nutrient or therapeutic agent in the treatment or prevention of insulin resistance.

Chromium↗

Effect of nutrition on tumor necrosis factor receptors in weight-gaining and -losing rats.

Previous studies showed that weight-gaining rats had greater retention and reduced turnover of 125I-labeled tumor necrosis factor (TNF)-alpha in the circulation compared with weight-losing animals. We therefore tested the hypothesis that protein-energy restriction with weight loss reduces the levels of soluble TNF-alpha receptor (sTNFR) and membrane TNFR (mTNFR) and the cellular expression of TNF-alpha mRNA. Twenty-six male rats weighing 200-220 g were fed a liquid formula diet for 10 days and divided equally into weight-gaining rats meeting all nutritional requirements (WG rats) and weight-losing rats with protein-energy restriction (WL rats). 125I-TNF-alpha binding was demonstrated in plasma and plasma membrane to proteins of molecular masses of 92 and 243 kDa, a finding identical to that seen with purified human p55. Excess unlabeled TNF-alpha displaced the binding showing its specificity. The degree of binding to plasma protein and liver plasma membrane was markedly reduced in WL rats. Northern analysis showed that the expression of p55 mRNA was increased in the lungs and reduced in kidneys of WL compared with WG rats. The expression of p75 mRNA was not influenced by the nutritional status. We conclude that levels of sTNFR and mTNFR were reduced in WL rats. Reduced sTNFR and liver mTNFR are not due to a reduction in the expression of either p55 or p75 mRNA in WL rats. Reduced mTNFR, together with reduced shedding of soluble receptors, may have a protective role in WL rats.

Animal Nutritional Physiological Phenomena↗

Increased oxidative stress in patients with congestive heart failure.

OBJECTIVES: We sought to study the markers of lipid peroxidation and defenses against oxidative stress in patients with varying degrees of heart failure. BACKGROUND: Despite advances in other areas of cardiovascular disease, the morbidity and mortality from congestive heart failure (CHF) are increasing. Data mainly from animal models suggest that free radical injury may promote myocardial decompensation. However, there are no studies in humans correlating the severity of heart failure with increased free radical injury and antioxidants. METHODS: Fifty-eight patients with CHF and 19 control subjects were studied. In addition to complete clinical and echocardiographic evaluations, the prognosis of these patients was established by measuring the levels of soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2). Oxidative stress was evaluated by measuring plasma lipid peroxides (LPO), malondialdehyde (MDA), glutathione peroxidase (GSHPx) and vitamin E and C levels. RESULTS: The patients' age range, cause of heart failure and drug intake were comparable across the different classes of heart failure. Heart failure resulted in a significant increase in LPO (p < 0.005), MDA (p < 0.005), sTNF-R1 (p < 0.005) and sTNF-R2 (p < 0.005). There was a significant positive correlation between the clinical class of heart failure and LPO, MDA, sTNF-R1 and sTNF-R2 levels. There was an inverse correlation between GSHPx and LPO. With increased lipid peroxidation in patients with CHF, the levels of vitamin C decreased, but vitamin E levels were maintained. CONCLUSIONS: These data demonstrate a progressive increase in free radical injury and encroachment on antioxidant reserves with the evolution of heart failure; they also suggest that oxidative stress may be an important determinant of prognosis. The therapeutic benefit of administering antioxidant supplements to patients with CHF should be evaluated.

Aged↗

Nutritional assessment.

Nutritional status is a dynamic entity that changes because of interactions between nutrient intake and absorption and requirements and disease. Clinically relevant nutritional assessment should determine whether the patient's nutritional status will decline in the absence of nutritional support. In addition, such assessment should predict complications in the absence of nutritional intervention. The role of different techniques--clinical body compositional, and functional--is discussed in this context.

Adult↗

31P-nuclear magnetic resonance studies of bioenergetic changes in skeletal muscle in malnourished human adults.

In previous studies, both animals and malnourished children receiving 25% of the protein-energy intake of a control group, resulting in a 25% weight loss, had lower ratios of phosphocreatine to beta-ATP and of phosphocreatine to inorganic phosphorus, higher free ADP concentrations, and lower free energy of ATP hydrolysis than the control group. Therefore, the effect of malnutrition on muscle energetics in adult humans was examined by using 31P-nuclear magnetic resonance spectroscopy in malnourished patients with a mean body mass index (BMI; in kg/m2) of 16.4 compared with healthy control subjects with a significantly higher body mass index of 24.5 (P < 0.005). The mean (+/- SEM) ratio of phosphocreatine (PCr) to ATP in the malnourished patients was 2.28 +/- 0.27, which was significantly lower than the ratio of 3.1 +/- 0.15 in control subjects (P < 0.02). The ratio of inorganic phosphorus (Pi) to ATP in malnourished patients was 0.33 +/- 0.04, which was significantly lower than the ratio of 0.48 +/- 0.03 in control subjects (P < 0.02), but the ratio of PCr to Pi was not significantly different from that in control subjects. There was a significant correlation between BMI and the ratio of PCr to ATP (P < 0.01) and of Pi to ATP (P < 0.01). These data suggest that progressive loss of BMI is associated with a relative loss of muscle creatine and phosphorus in relation to ATP. The findings were unlikely to have been due only to atrophy of fast-twitch fibers because such atrophy would have altered the ratio of PCr to Pi.

Adult↗

Changes in body composition and dietary intake induced by tumor necrosis factor alpha and corticosterone--individually and in combination.

Previous studies have shown that anorexia and reduced food intake are the main causes of weight loss in rats infused with tumor necrosis factor alpha (TNF-alpha), with no influence on corticosterone concentrations. In contrast, in clinical sepsis, muscle wasting due to increased catabolism is associated with increased corticosteroid concentrations. We hypothesized that in the rat model, corticosterone potentiates the catabolic effect of TNF-alpha in amounts that by itself does not influence muscle catabolism. Orally fed rats were divided into 3 treatment groups: continuous infusion of TNF-alpha (TNF; 100 microg x kg(-1) x d(-1)), corticosterone (Cort; 50 microg x g(-1) x d(-1)), or both (TNF+Cort). Each group was compared with a respective pair-fed (PF) group. In addition an ad libitum (AL)-fed group receiving an infusion of physiologic saline was studied to observe unrestricted food intake and weight gain. After 4 d of infusion, dietary intake and weight gain were significantly higher in the Cort and AL groups than in the TNF and TNF+Cort groups. Although wet liver weights and protein contents were significantly higher in the Cort, TNF, and TNF+Cort groups than in their respective PF group, the TNF and TNF+Cort groups had lower relative carcass weights. The weight and protein content of the diaphragm were lower and nitrogen excretion was higher in the TNF+Cort group than in the respective PF group. The results suggest that TNF-alpha plus corticosterone had a specific catabolic effect on the diaphragm. In addition, together they increased overall nitrogen excretion.

Animals↗

Feeding a low energy diet and refeeding a control diet affect glycolysis differently in the slow- and fast-twitch muscles of adult male Wistar rats.

Muscle glycogen concentrations in underfed (HYPO) and refed rats (RE) in an earlier study did not correlate with fatigue. We hypothesized that underfeeding slowed glycolysis in the slow-twitch soleus, but not in the fast-twitch extensor digitorum longus (EDL). Thirty adult male Wistar rats were randomly assigned to receive one of two isovolemic and micronutrient-complete liquid diets, a control (CN) energy-complete diet for 10 d or a diet 80% lower in energy (HYPO) for 7 d producing a 20% loss of initial weight. Rats were refed an energy-complete diet for 1 or 4 d (RE1, RE4). Rats were then anesthetized, and the soleus and EDL muscles of the hindlimbs were isolated and electrically stimulated in situ. The pre- and postfatigued muscles were freeze-clamped, lyophilized and stored at -70 degreesC until assayed for specific glycolytic and Krebs cycle metabolites. The HYPO diet caused significantly slower glycolysis in the stimulated soleus but not the EDL compared with the CN diet as supported by the following: 1) a lower fructose-1,6-bisphosphate (F-1,6-P2)/fructose-6-phosphate (F-6-P) ratio; 2) a greater glucose-6-phosphate (G-6-P)/lactate ratio; 3) a lower lactate/glycogen ratio; and 4) lower lactate concentration. Four days of refeeding normalized the F-1,6-P2/F-6-P ratio, but did not improve the lactate/glycogen or the G-6-P/lactate ratios. We conclude that undernutrition compromises glycolysis only in slow-twitch muscles and that 4 d of refeeding restores phosphofructokinase activity.

Analysis of Variance↗

Nutritional management of anorexia.

The prevalence of eating disorders, such as anorexia nervosa, is increasing in young adults, particularly young adult women. Sometimes, gastrointestinal complaints in patients with anorexia nervosa may lead to an erroneous diagnosis of gastrointestinal disease and unnecessary diagnostic studies and therapies. In contrast, patients with gastrointestinal disease may experience anorexia because of abdominal pain and other gastrointestinal symptoms induced by eating. In these patients, anorexia minimizes symptoms and can obscure the underlying gastrointestinal disease by "resting" the bowel. Therefore, a careful history and physical examination and laboratory tests are needed to make the correct diagnosis and begin appropriate treatment.

Adolescent↗

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease.

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic.

Actuarial Analysis↗

Immunonutrition.

The immune system is designed to protect the individual from foreign substances or organisms. It is expressed as cellular and humoral immunity. The former is dependent upon T lymphocytes and the latter on B lymphocytes, which become plasma cells and secrete antibodies. The immune system can be influenced by protein-energy malnutrition (PEM) and by catabolic illnesses such as sepsis and trauma, which in turn cause PEM. Specific trace element and vitamin deficiencies can also alter the immune state. However, overnutrition and obesity can also influence immune mechanisms. Obesity can promote the development of diabetes, which can alter the immune state. Finally, immunity becomes less effective with ageing and this process is enhanced by associated malnutrition.

Animals↗

Effect of hypoenergetic feeding and high-carbohydrate refeeding on muscle tetanic tension, relaxation rate, and fatigue in slow- and fast-twitch muscles in rats.

Studies using nuclear magnetic resonance have shown that undernutrition affects muscle performance and energetics. It is unclear to what extent underfeeding and refeeding influence the availability of muscle glycogen, net glycogenolysis, skeletal muscle wasting, and recovery. We hypothesized that muscle performance is independent of muscle size and weight, is specific to muscle type, and is unrelated to muscle glycogen concentrations. Slow- and fast-twitch muscles were studied in three groups of adult male Wistar rats: well-fed controls, hypoenergetically fed (Hypo) rats, and rats refed for 4 d after the hypoenergetic diet. Glycogen concentrations and net glycogenolysis; serum glucose, insulin, and protein concentrations; and muscle weight, protein, and cross-sectional area were studied relative to the performance of both types of muscles. Our study controlled for muscle size, weight, and type and electrolyte-micronutrient deficiency. Undernutrition affected muscle performance in five ways. First, compared with controls, fatigue increased only in the soleus muscles of Hypo rats yet the maximal relaxation rate (MRR) decreased in both the soleus and extensor digitorum longus (EDL) muscles. Second, muscle glycogen concentrations did not significantly correlate with fatigue in either the soleus or the EDL although net glycogenolysis was significantly correlated with fatigue in the soleus (r = -0.64; P > 0.01 < 0.05). Third, lower glycogen concentrations did not hinder net glycogenolysis in the EDL of Hypo rats or the soleus of refed rats. Fourth, muscle weight, size, and protein were dissociated from function. Fifth, refeeding did not restore muscle endurance; however, the MRR of the soleus normalized. In conclusion, glycogen values and muscle performance did not correlate but net glycogenolysis correlated with fatigue in the soleus. Also, there was a dissociation between muscle weight, size, and protein and muscle function during hypoenergetic feeding and refeeding.

Animals↗

Nutritional status and function in patients following Whipple procedure compared with controls.

OBJECTIVE: Despite the potential for nutritional deficits in patients undergoing pancreaticoduodenectomy or Whipple procedure, long-term assessment of nutritional status has largely been ignored. This study assessed nutritional status of 24 Whipple patients compared with matched post-cholecystectomy controls. METHODS: Clinical assessment was by subjective global assessment, body composition was assessed by bioelectric impedance analysis and functional assessment was by respiratory muscle strength and skeletal muscle function performed by electrical stimulation of the ulnar nerve of the wrist and hand-grip dynamometry. RESULTS: Whipple patients studied 4.6+/-0.7 years since surgery and controls (4.8+/-0.7 years since surgery) were all judged clinically to be in a good nutritional state. Compared with controls, Whipple patients had significantly lower body weight (Whipple: 72.5+/-2.8 kg, control: 83.9+/-3.3 kg, p<0.05) however, the mean body weight of both Whipple and controls was above ideal weight (Whipple: 113.3+/-4.3%, control: 122.3+/-3.7% p = NS). No significant differences in functional performance were observed between groups. Energy intake of Whipple and controls was also comparable. In the Whipple group, neither the extent of gastric resection or the pathological diagnosis had an effect on the nutritional parameters studied. CONCLUSIONS: Long-term follow-up of patients having undergone Whipple procedure failed to reveal the presence of any nutritional or functional deficits suggesting that a full nutritional recovery is possible after this surgery.

Aged↗

Effects of hypocaloric feeding and refeeding on myocardial Ca and ATP cycling in the rat.

Hypocaloric feeding (HCF) depresses heart function causing cardiac atrophy, bradycardia, and decreased cardiac output. We tested the hypothesis that HCF results in decreased myocardial Ca- and ATP cycling. We reduced protein-calorie intake of adult rats by 20% for 7 days and then allowed them to recover for 3 days. Changes in ionized Ca concentration (nM/s) of 2.5% myocardial homogenates that were attributable to the Ca-ATPase pump and Ca-release channel (CRC), respectively, of the sarcoplasmic reticulum (SR) were depressed 41 and 85% by HCF from 61.6 +/- 9.4 and 24.7 +/- 3.3, to 36.1 +/- 2.8 and 3.6 +/- 2.9. Activity of the Ca-pump was restored after 3 days of refeeding, whereas the CRC remained 23% depressed (all p < 0.05). Additionally, the CRC activity was inhibited to a 3-fold greater extent than controls by HCF, but was disinhibited within one day of refeeding. The greater effect on CRC than Ca-pump activity resulted in net Ca-uptake being unaffected by HCF. In addition to depression of Ca-cycling, ATP sythetase and total ATPase activities (IU/g), respectively, were depressed 20 and 15% by HCF from 174 +/- 19 and 51.3 +/- 3.8 to 140 +/- 15 and 43.7 +/- 4.7, but were restored to control values within one day of refeeding. We conclude that HCF produces a compensatory, reversible, and asymmetric downregulation and inhibition of Ca-cycling, with the CRC being preferentially affected.

Adenosine Triphosphate↗