Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The excitotoxin, N-methyl-D-aspartic acid (NMDA), was used to lesion cell bodies, but not fibers-of-passage, in the paraventricular hypothalamus. Bilateral injections of NMDA (12.6 nmol/100 nl) were made into the paraventricular hypothalamus in halothane-anesthetized male Sprague-Dawley rats. Water intake, food intake, urine output and body weight were measured daily for 26 days after lesioning. Lesioned rats exhibited a modest, but significant, reduction in the rate of gain of body weight, which was most closely correlated with decreases in food intake. Water intake and urine output were not significantly different among the groups. Resting blood pressure, heart rate and baroreflex sensitivity (using the infusion of phenylephrine method) were similar in conscious animals of both groups, 4-5 weeks after lesioning. Neuronal loss, primarily of parvocellular elements, was evident in the paraventricular hypothalamus and neuronal loss frequently extended into the ventro-medial thalamus adjacent to the paraventricular hypothalamus in NMDA-lesioned rats. In a second experiment, injections of NMDA were given acutely into the paraventricular hypothalamus of halothane-anesthetized rats. Upon recovery from anesthesia, behavioral excitation and increases in blood pressure and heart rate were evident for 1-2 hr. Histological examination of hearts taken 48 hr after injection of NMDA revealed a largely mononuclear inflammatory infiltration, hyperemia and myocardial hemorrhage and focal myocardial necrosis. Inflammatory and degenerative changes were most prominent in the left ventricular subendocardium. The cardiomyopathy possessed similarities with catecholamine-induced myocardial necrosis. The results indicated that NMDA-induced lesions of parvocellular elements of the paraventricular hypothalamus did not cause hyperphagia or obesity or alter the resting systemic circulatory function. However, an inflammatory cardiomyopathy, termed "excitotoxin-induced myocardial necrosis", was associated with injections of NMDA into the hypothalamus. Excitotoxin-induced myocardial necrosis may complicate any hemodynamic studies performed in rats in which lesions of the CNS have been produced by means of application of excitotoxins.
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PMID:Excitotoxic lesions of the paraventricular hypothalamus: metabolic and cardiac effects. 220 Sep 75

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
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PMID:Acromegaly in 14 cats. 240 66

The medical records of 14 hyperthyroid cats with thyroid carcinoma were analyzed retrospectively regarding historical, physical, laboratory, and thyroid scintiscan findings, treatment, and treatment outcome. Breed predilection was not detected, and older castrated male cats were most commonly affected. The most common clinical signs detected by owners were weight loss, polydipsia, polyuria, polyphagia, hyperactivity, and anorexia. Physical examination findings included tachycardia, palpable cervical mass, hyperactivity, cardiac murmur, and abnormal coat. Common abnormal laboratory findings were high serum thyroxine and triiodo-thyronine concentrations and high serum alanine transaminase, alkaline phosphatase, and aspartate transaminase activities. Azotemia, hyperphosphatemia, and hyperglycemia were noticed less frequently. The most common thyroid scintiscan findings were multiple nodular areas of high radionuclide uptake in the cervical region, thoracic inlet, and cranial mediastinum. The most common morphologic diagnosis was mixed compact and follicular carcinoma, with follicular and papillary carcinomas being less common. Most cats responded well to treatment of the thyroid tumor, with rapid resolution of the historical and physical examination findings. The most common necropsy findings were local tumor invasion, regional lymph node metastases, cardiomyopathy, and interstitial nephritis.
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PMID:Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981-1986). 318 90

The JCR:LA-cp rat is obese, insulin resistant, and hyperlipidemic, and the males develop atherosclerosis and ischemic myocardial disease. Benfluorex at 35-40 mg.kg-1 body weight was administered in the food from 10 to 14 weeks of age and resulted in an initial 50% decrease in food consumption. Body weights of male and female rats initially decreased by about 7% and thereafter remained relatively constant, whereas control animals gained about 28% in weight over the treatment period. Pair-fed rats showed body weights virtually identical with those of benfluorex-treated animals. Benfluorex treatment and pair feeding decreased serum triacylglycerol concentrations by about 50%; there was a preferential loss of triacylglycerols containing longer chain fatty acids in the males, whereas this selectivity was not seen in the females. Hyperinsulinemic euglycemic insulin clamp studies were performed using [1-3H]glucose, a tracer that allows for the measurement of total glucose turnover, including hepatic uptake and release. In male cp/cp rats, hyperinsulinemia does not stimulate total glucose turnover, reflecting the very severe insulin resistance, and neither benfluorex treatment nor pair feeding increased total glucose turnover. Hyperinsulinemia in male cp/cp rats decreases hepatic glucose output, and benfluorex treatment or pair feeding reduced this insulin-mediated diversion of glucose to hepatic lipid synthesis. Hyperinsulinemia increases total glucose turnover in female cp/cp rats, and this was not increased further by benfluorex treatment or pair feeding. These effects emphasize the sex-specific differences in metabolic response of the rats to hyperinsulinemia and benfluorex treatment. Benfluorex ameliorates the obesity-insulin resistance-hyperlipidemia syndrome in this experimental model mainly by decreasing hyperphagia, with an accompanying improvement in hepatic glucose metabolism and a related reduction in hypertriglyceridemia.
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PMID:Effects of benfluorex on serum triacylglycerols and insulin sensitivity in the corpulent rat. 896 Mar 76

The present investigation was undertaken to study the effects of chronic oral ramipril (1 mg/kg) treatment in streptozotocin (STZ) induced diabetic rats. Single tail vein injection of STZ (45 mg/kg, i.v.) produced a diabetic state exhibiting all the cardinal symptoms such as loss of body weight, polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinaemia and hyperglycaemia. The diabetic state was also found to be associated with bradycardia, hypothyroidism, cardiac depression and cardiomyopathy. Ramipril treatment prevented STZ-induced hypertension, bradycardia, hypothyroidism, hyperchosesterolaemia and partially the cardiomayopathy. Ramipril treatment could not, however prevent STZ-induced loss of body weight, polyuria, polydipsia, polyphagia, hyperglycaemia, hypoinsulinaemia, hypertriglyceridaemia and cardiac depression. Our data suggests that ramipril has a few beneficial effects in the STZ-treated diabetic rats.
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PMID:Effects of chronic ramipril treatment in streptozotocin-induced diabetic rats. 1023 57

Obesity-related diseases now threaten to reach epidemic proportions in the United States. Here we review in a rodent model of genetic obesity, the fa/fa Zucker diabetic fatty (ZDF) rat, the mechanisms involved in the most common complications of diet-induced human obesity, i.e., noninsulin-dependent diabetes mellitus, and myocardial dysfunction. In ZDF rats, hyperphagia leads to hyperinsulinemia, which up-regulates transcription factors that stimulate lipogenesis. This causes ectopic deposition of triacylglycerol in nonadipocytes, providing fatty acid (FA) substrate for damaging pathways of nonoxidative metabolism, such as ceramide synthesis. In beta cells and myocardium, the resulting functional impairment and apoptosis cause diabetes and cardiomyopathy. Interventions that lower ectopic lipid accumulation or block nonoxidative metabolism of FA and ceramide formation completely prevent these complications. Given the evidence for a similar etiology for the complications of human obesity, it would be appropriate to develop strategies to avert the predicted epidemic of lipotoxic disorders.
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PMID:Diseases of liporegulation: new perspective on obesity and related disorders. 1115 47

Mitochondrial oxidation of long-chain fatty acids provides an important source of energy for the heart as well as for skeletal muscle during prolonged aerobic work and for hepatic ketogenesis during long-term fasting. The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of beta-oxidation. The shuttle consists of three enzymes (carnitine palmitoyltransferase 1, carnitine acylcarnitine translocase, carnitine palmitoyl-transferase 2) and a small, soluble molecule, carnitine, to transport fatty acids as their long-chain fatty acylcarnitine esters. Carnitine is provided in the diet (animal protein) and also synthesized at low rates from trimethyl-lysine residues generated during protein catabolism. Carnitine turnover rates (300-500 micromol/day) are <1% of body stores; 98% of carnitine stores are intracellular (total carnitine levels are 40-50 microM in plasma vs. 2-3 mM in tissue). Carnitine is removed by urinary excretion after reabsorption of 98% of the filtered load; the renal carnitine threshold determines plasma concentrations and total body carnitine stores. Because of its key role in fatty acid oxidation, there has long been interest in the possibility that carnitine might be of benefit in genetic or acquired disorders of energy production to improve fatty acid oxidation, to remove accumulated toxic fatty acyl-CoA metabolites, or to restore the balance between free and acyl-CoA. Two disorders have been described in children where the supply of carnitine becomes limiting for fatty acid oxidation: (1) A recessive defect of the muscle/kidney sodium-dependent, plasma membrane carnitine symporter, which presents in infancy with cardiomyopathy or hypoketotic hypoglycemia; treatment with oral carnitine is required for survival. (2) Chronic administration of pivalate-conjugated antibiotics in which excretion of pivaloyl-carnitine can lead to carnitine depletion; tissue levels may become low enough to limit fatty acid oxidation, although no cases of illness due to carnitine deficiency have been described. There is speculation that carnitine supplements might be beneficial in other settings (such as genetic acyl-CoA oxidation defects--"secondary carnitine deficiency", chronic ischemia, hyperalimentation, nutritional carnitine deficiency), but efficacy has not been documented. The formation of abnormal acylcarnitines has been helpful in expanded newborn screening programs using tandem mass-spectrometry of blood spot acylcarnitine profiles to detect genetic fatty acid oxidation defects in neonates. Carnitine-deficient diets (vegetarian) do not have much effect on carnitine pools in adults. A modest 50% reduction in carnitine levels is associated with hyperalimentation in newborn infants, but is of doubtful significance. The above considerations indicate that carnitine does not become rate-limiting unless extremely low; testing the benefits of nutritional supplements may require invasive endurance studies of fasting ketogenesis or muscle and cardiovascular work.
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PMID:Carnitine deficiency disorders in children. 1559 Oct 2

Monosomy 1p36 is the most common terminal deletion syndrome seen in humans, occurring in approximately 1 in 5,000 live births. Common features include mental retardation, characteristic dysmorphic features, hypotonia, seizures, hearing loss, heart defects, cardiomyopathy, and behavior abnormalities. Similar phenotypes are seen among patients with a variety of deletion sizes, including terminal and interstitial deletions, complex rearrangements, and unbalanced translocations. Consequently, critical regions harboring causative genes for each of these features have been difficult to identify. Here we report on five individuals with 200-823 kb overlapping deletions of proximal 1p36.33, four of which are apparently de novo. They present with features of monosomy 1p36, including developmental delay and mental retardation, dysmorphic features, hypotonia, behavioral abnormalities including hyperphagia, and seizures. The smallest region of deletion overlap is 174 kb and contains five genes; these genes are likely candidates for some of the phenotypic features in monosomy 1p36. Other genes deleted in a subset of the patients likely play a contributory role in the phenotypes, including GABRD and seizures, PRKCZ and neurologic features, and SKI and dysmorphic and neurologic features. Characterization of small deletions is important for narrowing critical intervals and for the identification of causative or candidate genes for features of monosomy 1p36 syndrome.
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PMID:Refinement of causative genes in monosomy 1p36 through clinical and molecular cytogenetic characterization of small interstitial deletions. 2063 59

Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta and gamma) play a key role in metabolic regulatory processes and gene regulation of cellular metabolism, particularly in the cardiovascular system. Moreover, PPARs have various extra metabolic roles, in circadian rhythms, inflammation and oxidative stress. In this review, we focus mainly on the effects of PPARs on some thermodynamic processes, which can behave either near equilibrium, or far-from-equilibrium. New functions of PPARs are reported in the arrhythmogenic right ventricular cardiomyopathy, a human genetic heart disease. It is now possible to link the genetic desmosomal abnormalitiy to the presence of fat in the right ventricle, partly due to an overexpression of PPARgamma. Moreover, PPARs are directly or indirectly involved in cellular oscillatory processes such as the Wnt-b-catenin pathway, circadian rhythms of arterial blood pressure and cardiac frequency and glycolysis metabolic pathway. Dysfunction of clock genes and PPARgamma may lead to hyperphagia, obesity, metabolic syndrome, myocardial infarction and sudden cardiac death, In pathological conditions, regulatory processes of the cardiovascular system may bifurcate towards new states, such as those encountered in hypertension, type 2 diabetes, and heart failure. Numerous of these oscillatory mechanisms, organized in time and space, behave far from equilibrium and are "dissipative structures".
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PMID:PPARs, Cardiovascular Metabolism, and Function: Near- or Far-from-Equilibrium Pathways. 2070 50

Normalization of hyperglycemia, hyperlipidemia and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. The present study investigated the effects of the fruit juice obtained from Emblica officinalis on myocardial dysfunction in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats were treated with E officinalis fruit juice for eight weeks. Injection of STZ produced loss of body weight, polydypsia, polyphagia, hyperglycemia, hypoinsulinemia and dyslipidemia. It also produced hypertension, bradycardia, hypertrophy and myocardial functional alterations associated with an increase in serum lactate dehydrogenase and creatinine kinase-MB levels. Treatment with the fruit juice not only prevented STZ-induced loss of body weight, increases in water and food intake, increases in serum glucose levels and disturbed lipid profile, but also an increase in serum lactate dehydrogenase and creatinine kinase-MB levels, and increased myocardial hypertrophy and cardiomyopathy. There was an increase in the area under the curve (AUC) for glucose, and a decrease in AUC(insulin) was observed in diabetic rats; treatment decreased AUC(glucose) but not AUC(insulin) or hyperinsulinemia. There was a decrease in antioxidant enzyme levels (in superoxide dismutase, reduced glutathione and catalase) in diabetic hearts, which could be improved by treatment with fruit juice. The present data suggest that fruit juice may be beneficial for the treatment of myocardial damage associated with type 1 diabetes mellitus. The activity of E officinalis fruit juice can be attributed to the concentration of polyphenol present.
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PMID:Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit. 2206 39


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