Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histidinemia was found in 3 of 4 siblings in one family, while a fatal encephalopathy with mental retardation was present in two of them and in the fourth child who did not have histidinemia. Biochemical studies of the histidinemic subjects showed elevated histidine levels in urine, CSF, and brain, while in a few urine samples histidine related imidazole compounds were found. Plasma levels of other amino acids were positively correlated with plasma histidine levels. Obesity and heart abnormalities appeared to be associated with the encephalopathy, which is probably of a new type. The histidinemia appears to be unrelated to the mental retardation or the encephalopathy in this family.
 ...
PMID:Sibship with histidinemia and an unrelated encephalopathy. Clinical and biochemical studies. 61 85

A 39-year-old woman presented with a 2-month history of repeated severe headache, nausea and diplopia. On admission she was obese with bilateral papilledma and abducens weakness. Mass lesion and sinus thrombosis were ruled out by brain CT and angiography. CSF pressure was normal initially. CSF pressure fluctuated with menstrual cycle, sometimes showing over 600 mmH2O with worsening of the symptoms. She was diagnosed as benign intracranial hypertension (BIH). Diuretics did not improve the symptoms, and visual disturbances ensued and deteriorated. A spinal subarachnoid space-peritoneal shunt was inserted to control CSF pressure, showing rapid improvement of headache and diplopia but visual disturbances remained almost unchanged. Optic nerve sheath fenestration was performed without improvement of visual deterioration. We postulated multiple factors such as obesity, menstrual abnormality, iron deficiency anemia and analgesic drugs played important roles to produce BIH in this case. Careful quantitative perimetry should be done to decide a suitable time for surgical treatment in BIH.
 ...
PMID:[A case of benign intracranial hypertension with fluctuated symptoms and CSF pressure synchronized with menstrual cycle]. 149 Mar 15

Of the many factors that influence food intake, there is strong evidence that opioid and CCK peptides, which stimulate feeding and elicit satiety, respectively, are important components that may act in concert to regulate energy balance. Cholecystokinin peptides have been isolated in both the brain and gastrointestinal tract, and changes in concentration in the brain and in plasma have been shown to vary with feeding. Peripherally injected CCK has been shown to elicit satiety in many species, including humans, an effect that may be mediated in the CNS via the vagus. In several species, most notably the sheep, direct injection into the CSF potently decreases food intake. Questions remaining regarding the role of CCK peptides in eliciting satiety include the sites and mechanisms of action. It is unknown whether CCK acts directly on receptors, indirectly on some other parameter, or as a neurotransmitter. Although opioid peptides have also been localized in portions of both the periphery and brain, a specific physiological role for their presence has not yet been determined. Opioid peptides from three families--endorphins, enkephalins, and dynorphins--have been shown to stimulate feeding in various species. They have been active at several opioid receptor types in the CNS, but there is limited evidence to suggest they affect food intake when administered peripherally. In contrast, peripheral injection of opiate antagonists has effectively decreased food intake, an observation that led to the original hypothesis that opioids were involved in the hunger component in the control of food intake and that excess concentrations might be involved in the development of obesity. An increasing body of evidence supports the concept that opioid and CCK peptides may interact to control food intake, but the evidence is more suggestive than conclusive.
 ...
PMID:Role of cholecystokinin and opioid peptides in control of food intake. 286 68

1. CCK-peptides are distributed throughout the whole brain with the exception of the cerebellum. 2. There is strong evidence that they act as neuromodulators on the noradrenergic, opioid and mainly dopaminergic system. 3. CCK reduces food-intake. However, tolerance occurs, when chronically given. Thus, potential benefits in the treatment of obesity seem unlikely. 4. CCK increases threshold and tolerance to electrically and thermally induced cutaneous pain. CCK yields relief of pain in colic and ischaemic pain. 5. To date, results about CCK-content in CSF and post-mortem-brain in various psychiatric and neurological diseases related to the dopaminergic system are equivocal. 6. Treatment studies do not provide evidence for beneficial effects of CCK-peptides in schizophrenia.
 ...
PMID:Cholecystokinin. 307 40

Conjugated MHPG is an indicator of the adrenergic tonus having clinical use in the follow-up of affective disorders, arterial hypotension, anorexia nervosa and recently of obesity. Little is known about the significance of the unconjugated, free MHPG in various body fluids. Nineteen healthy and 38 obese children were studied as regards the urinary excretion of free MHPG (MHPGF), conjugated MHPG (MHPGC), total MHPG (MHPGT) and also free noradrenaline (NA) valnillyl mandelic acid (VMA) and metanephrines (MN). Part of the obese received a short-term course of drug therapy (diethyl-propion-DEP or thyroid extract) and were subjected to a low-carbohydrate diet containing 800-1000 calories a day. The same urinary determinations were made after diet alone or after diet and drug therapy. MHPGC and MHPGT were significantly higher in the obese children. The level of MHPGF was essentially the same in both groups and did not change significantly following any drug or after diet alone. It was concluded that esterification mechanisms are not involved in the pathological states expressing high or low levels of MHPGC. Suggestion is made that these mechanisms may not be saturated unless huge amounts of MHPG outflow from the brain into CSF.
 ...
PMID:Free 3-methoxy-4-hydroxyphenylglycol (MHPG) in human urine: metabolic routes, biochemical and clinical significance in healthy and obese children. 341 39

The etiology to the empty sella syndrome (ESS) is not known. Increased intracranial pressure (ICP) has been suggested to be one of the possible causes. In the present study the CSF circulation was analyzed in 48 subjects with ESS with gamma cisternography, pneumoencephalography (PEG) and computed tomography (CT). In 80% of the subjects the CSF circulation was retarded with convexity block which was combined with widened CSF transport pathways and basal cisterns. These findings were correlated with the clinical signs and symptoms, most of which seemed to be related to the imparied CSF circulation (i.e. impared memory, balance disturbances, cerebellar ataxia, papilledema, hypertension and pituitary disorders). Headache, psychiatric symptoms, visual field defects and obesity, however, were not related to the impaired CSF circulation. It is concluded that impaired CSF dynamics leading to intermittent increase of ICP has a major impact on the development of the ESS and that most of the patients' complaints are related to this disturbance. Thus it is important to obtain information of the CSF dynamics concurrent with the diagnosis of ESS. For this purpose PEG or CT may be used as the first examination. Moreover, the patient should be examined at least every second year for symptoms and signs of progressive impairments of the CSF circulation.
 ...
PMID:CSF circulation in subjects with the empty sella syndrome. 725 14

A central dysregulation of several neuropeptides could be at the origin of the marked hyperphagia of the obese Zucker rat, a well-known animal model used for the study of obesity. Neuropeptide Y (NPY), which stimulates food intake and increases early in life in obese rats, plays a major role in the development of this hyperphagia. The aim of our experiment was to test a proposed NPY antagonist namely PYX-2 in obese hyperphagic Zucker rats in order to know if it could be an interesting drug for limiting their food intakes. Four doses of PYX-2 (50-1000 pmol) were injected in a counterbalanced order in the lateral brain ventricles of 10 adult male Zucker rats. Food intake was recorded 0.5, 1, 2, 3, 6, and 23 h after PYX-2 injection and compared either to the rat's spontaneous food intake or to the food intake following injection of artificial CSF (vehicle) only. It was not modified by any dose of PYX-2 whatever the time considered (1 h after injection: 4.3 +/- 0.5 (1000 pmol) vs 4.6 +/- 0.8 (CSF) g; 23 h period: 27.0 +/- 1.9 (1000 pmol) vs 26.6 +/- 2.9 (CSF) g; N.S.). Thus, PYX-2, the putative NPY antagonist, totally failed to inhibit food intake in the obese rats. The absence of effect of PYX-2 on food intake can be explained by the structure of PYX-2, a modified 27-36 amino acid sequence that may not be recognized by the Y1-type NPY receptors which are involved in the regulation of feeding behavior.
 ...
PMID:Putative neuropeptide Y antagonist failed to decrease overeating in obese Zucker rats. 789 51

A 29 year-old woman with SLE was admitted to our department due to severe remitting headaches. Following investigation a high degree of intra cranial pressure was determined. Several years ago a similar finding was diagnosed, and the disease was brought into remission by the administration of periodical pulses of high dose intravenous immunoglobulins. Benign intracranial hypertension (BIH) is an uncommon presentation of neuro-psychiatric SLE. In this patient several risk factors of BIH (obesity, steroid therapy, and SLE) assembled and elicited a severe presentation of the disorder which became more resistant to therapy. Several pathogenic pathways tie BIH with SLE as thrombotic obliteration of cerebral arteriolar and venous systems and immune complex deposition within the arachnoid villi (that are responsible for CSF absorption). As shown in this care report of BIH, clinical findings do not always parallel various imaging techniques as MRI and CT brain scans.
 ...
PMID:Pseudotumour cerebri in SLE. 860 94

Hyperleptinemia is an essential feature of human obesity. Total body fat mass > % body fat > BMI are the best predictors of circulating leptin levels. Although ob gene is differentially expressed in different fat compartments, apart from total body fat, upper or lower body adiposity or visceral fat does not influence basal leptin levels. Similarly, age, basal glucose levels, and ethnicity do not influence circulating leptin levels. Only in insulin-sensitive individuals do basal levels of insulin and leptin correlate positively even after factoring in body fat. Diabetes does not influence leptin secretion in both lean and obese subjects per se. Independent of adiposity, leptin levels are higher in women than in men. This sexual dimorphism is also present in adolescent children. In eating disorders anorexia nervosa and bulimea nervosa, leptin levels are not upregulated but simply reflect BMI and probably body fat. In spite of strong correlation between body fat and leptin levels, there is great heterogeneity in leptin levels at any given index of body fat. About 5% of obese populations can be regarded as "relatively" leptin deficient which could benefit from leptin therapy. Leptin has dual regulation in human physiology. During the periods of weight maintenance, when energy intake and energy output are equal, leptin levels reflect total bodyfat mass. However, in conditions of negative (weight-loss programs) and positive (weight-gain programs) energy balances, the changes in leptin levels function as a sensor of energy imbalance. This latter phenomenon is best illustrated by short-term fasting and overfeeding experiments. Within 24 h of fasting leptin levels decline to approximately 30% of initial basal values. Massive overfeeding over a 12-h period increases leptin levels by approximately 50% of initial basal values. Meal ingestion does not acutely regulate serum leptin levels. A few studies have shown a modest increase in leptin secretion at supraphysiological insulin concentrations 4-6 h following insulin infusion. Under in vitro conditions, insulin stimulates leptin production only after four days in primary cultures of human adipocytes, which is apparently due to its trophic effects and an increased fat-cell size. Similar to other hormones, leptin secretion shows circadian rhythm and oscillatory pattern. The nocturnal rise of leptin secretion is entrained to mealtime probably due to cumulative hyperinsulinemia of the entire day. Like other growth factors and cytokines, leptin binding proteins including soluble leptin receptor are present in human serum. In lean subjects, the majority of leptin circulates in the bound form whereas in obese subjects, the majority of leptin is present in the free form. When free-leptin levels are compared between lean and obese subjects, even more pronounced hyperleptinemia in obesity is observed than that reported by measuring total leptin levels. During short-term fasting, free-leptin levels in lean subjects decrease in much greater proportion than those in obese subjects. In lean subjects with a relatively small energy store and particularly during food deprivation, leptin circulating predominantly in the bound form could be the mechanism to restrict its availability to hypothalamic leptin receptors for inhibiting leptin's effect on food intake and/or energy metabolism. Unlike marked changes in serum leptin, CSF leptin is only modestly increased in obese subjects and the CSF leptin/serum leptin ratio decreases logarithmically with increasing BMI. If CSF leptin levels are any indication of brain interstitial fluid levels, then hypothalami of obese subjects are not exposed to abnormally elevated leptin concentrations. In the presence of normal leptin receptor (functional long form, i.e., OB-Rb) mRNA expression and in the absence of leptin receptor gene mutations, it is logical to assume defective leptin signaling and/or impaired affector system(s) are the likely causes of leptin resistance in
 ...
PMID:Clinical aspects of leptin. 952 71

The authors present two middle-aged female patients with empty sella revealed at imaging studies (CT, MRI). Their main complaint was severe fronto-parietal and fronto-temporal headache. Physical examination showed obesity, hypertension, and local hypersensitivity on deep palpation and percussion in the above-mentioned regions, in both cases. Endocrine function of pituitary gland, visual fields and fundi were normal as was EEG. The CSF composition and pressure also showed no abnormalities. The diagnostic and therapeutic problems of empty sella syndrome are discussed.
 ...
PMID:[Empty sella syndrome]. 1046 58


1 2 3 4 5 6 Next >>