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)

A case of advanced cervical carcinoma of the uterus with ectopic adrenocorticotrophic hormone (ACTH) syndrome is described. The patient was seen for general malaise 21 months after surgical treatment of the primary lesion whose histology was undifferentiated small cell carcinoma of the uterine cervix. She had extensive metastases in the liver and the abdominal wall. In addition to the typical clinical manifestations of Cushing's syndrome such as moon face, central obesity and acne vulgaris, hyperglycemia was so severe that she was in a hyperosmolar non-ketotic coma. Endocrinological examinations revealed elevated plasma ACTH and cortisol, and urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids, which were not suppressed by high-dose dexamethasone administration. Based on these clinical and laboratory findings, a diagnosis of ectopic ACTH syndrome was made. Among the results of other endocrinological examinations conducted to find the etiological cause of the hyperglycemic coma, which seemed to be unusual for ectopic ACTH syndrome, the plasma somatostatin level was abnormally high. Metastatic tumors in the liver obtained at the time of autopsy contained large amounts of both ACTH and somatostatin, and gel filtration studies revealed that the peptides produced by the tumor had the molecular sizes of the biologically active forms of the respective peptides. These observations suggest possible involvement of the somatostatin in deteriorating glucose intolerance to develop hyperglycemic hyperosmolar non-ketotic coma as a drastic disturbance of metabolism.
 ...
PMID:A case of cervical carcinoma of the uterus presenting with hyperosmolar non-ketotic coma as a manifestation of ectopic adrenocorticotropic hormone syndrome. 164 12

We report a case of Klinefelter's syndrome who developed a decrease of serum gonadotropin levels, particularly LH, after CyA treatment for complicated focal glomerulosclerosis (FGS). A 38-year-old man suffering from general malaise and pretibial edema was diagnosed FGS by renal biopsy in October 1988, and was referred to our hospital for further evaluation and treatment for FGS in December 1988. He was not married, and closer anamnesis revealed that he had had impaired seminal ejaculation from the age of 30. The physical examination showed 37% obesity, scanty body hair, pretibial edema and small bilateral testes (3.0 x 1.5cm). Laboratory findings included marked proteinuria (5.3g/day) and mild renal dysfunction (serum creatinine 1.3mg/dl, glomerular filtration rate 57.2ml/min). Endocrinologically, high basal levels of LH and FSH (133.6mIU/ml and 93.7mIU/ml, respectively) and the hyperresponses of LH and FSH to LH-RH stimulation were found, but the other pituitary hormone levels, thyroid and adrenal status, were in the normal range. In testicular biopsy, nodularly proliferated Leydig cells and no seminal tubules could be seen. The chromosome analysis showed 47,XXY karyotype, which confirmed the diagnosis of Klinefelter's syndrome in this patient. From 9 January 1989, CyA (6mg/Kg.day) was orally administered for 4 weeks in order to treat for FGS. After CyA administration, basal levels of LH and FSH remarkably decreased, particularly LH, and their decrease lasted for at least 6 weeks after cessation of CyA (final levels; LH 28.2mIU/ml, FSH 69.8mIU/ml). On the other hand, serum testosterone level was low normal or slightly under normal, and no apparent changes could be seen during CyA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cyclosporine A (CyA)-induced decrease of serum gonadotropin levels in a case of Klinefelter's syndrome. 190 51

CCK appears to regulate short-term control of food intake by acting as a satiety signal. Larger doses of CCK may decrease food intake by aversive actions (malaise, nausea, cramps), presumably by effects on gastrointestinal motility. In rats and most likely humans CCK is released from the upper intestine after a mixed meal and appears to activate afferent vagal fibers by causing pyloric contraction with resultant gastric distention or directly binding to the gastric afferent vagus which courses to the nucleus solitarius with further projections to the paraventricular nucleus and ultimately the ventromedial hypothalamus. Peripherally released CCK may also bind to CNS receptors in the area postrema overlying the nucleus solitarius. Central nervous system CCK released from the paraventricular nucleus may also exert a satiety effect. The satiety effect of CCK appears to be a physiologic action of the peptide since antibodies to CCK and CCK receptor antagonists can increase food intake. CCK is probably just one of several satiety signals but can cause a profound decrease in food intake when administered exogenously in pharmacologic doses. Administration of exogenous CCK, as well as endogenous CCK released by oral protease inhibitors, can decrease food intake in humans. Studies designed to examine the effect of chronic administration of CCK on food intake will be necessary to determine if the peptide has a role in the management of obesity and bulimia.
 ...
PMID:Role of cholecystokinin in the control of food intake. 269 51

One hundred and eighty patients had a jejunoileal bypass performed during the years 1971-1982. By leaving only 14 in. (35 cm) of intestine in continuity a mean weight loss of 34.4 per cent (s.d. = 8.5) was achieved over 2 years and, unless the operation had to be reversed for complications, this weight loss was maintained. The improvement in quality of life for a majority of patients should not be undervalued. Two-thirds of patients required admission for complications and eight patients died (4 per cent). Many of these problems were provoked by an inability to control eating. There have been no hospital deaths since 1976 which we attribute to better management of complications and a policy of early reversal for patients with excessive weight loss and signs of metabolic failure. Despite performing jejunoileal bypass less often in recent years we are still frequently reversing patients with electrolyte disturbances, metabolic failure, urinary calculi or arthritis. Thirty patients (16.7 per cent) have been reversed, half more than 5 years after bypass. Metabolic failure may occur even after many years of stable weight reduction. Because this is not well known the insidious onset of new weight loss and malaise may not be recognized, or not associated with the bypass many years before. Indefinite outpatient surveillance is mandatory. Changes in the operation have not significantly affected results. There has been no serious liver dysfunction in the 7:7:CJ group but this may reflect better management of lesser metabolic disturbances. Jejunoileal bypass remains the most effective operation for gross obesity and, with experience, can be performed safely. However, the complication rate and difficulty maintaining satisfactory follow-up on large numbers of young patients makes it an unacceptable procedure on any major scale.
 ...
PMID:A 13-year review of jejunoileal bypass. 397 Nov 27

Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide.
 ...
PMID:Rapid development of tolerance to the behavioural actions of cholecystokinin. 630 Jun 93

There is now extensive evidence that jejunioleal bypass (JIB) surgery reduces food intake in obese patients, and that in most cases this is the primary cause of their postoperative weight loss. Associated with the reduced food consumption are other behavioral changes, including alterations in meal patterns, appetite ratings, taste responsiveness, and food-related attitudes. Experimental animal research indicates that JIB surgery also reduces food intake in obese rats and alters their feeding patterns. The hypophagia and weight loss produced by the surgery in rats is dependent upon both the degree and type of obesity. The exact mechanism(s) by which JIB surgery suppresses food intake remains to be determined, although recent animal research implicates both visceral malaise and overstimulation of the lower ileum as contributing factors.
 ...
PMID:Appetitive behavior after jejunoileal bypass. 703 Sep 89

A 61-year-old woman with hyper-catecholaminemia and hyper-glucocorticoidemia due to a mixed tumor of the right adrenal gland is described. The patient, who had been medicated for hypertension since 1977, complained of thirst and general malaise in 1986. Body weight loss was remarkable. There was neither absolute truncal obesity nor moon face. In September 1986, her blood pressure was 180/110 mmHg and blood glucose level was 400mg/dl. Noradrenaline levels in plasma and in urine were remarkably elevated (1659 pg/ml and 120 micrograms/day, respectively), and adrenaline levels were also high (397 pg/ml in plasma, 34 micrograms/day in urine). Plasma cortisol and urinary 17-OHCS were elevated (39.2 micrograms/dl and 11.9 mg/day, respectively). Plasma ACTH was in the normal range (42.6 pg/ml). Oral administration of neither 1mg nor 8 mg of dexamethasone suppressed plasma cortisol or ACTH levels. Both 131I-metaiodobenzylguanidine and 131I-adosterol accumulated in the right adrenal gland. In 1987 the adrenal tumor (3.0 x 3.5 cm, 30 g) was resected. After the operation, her blood pressure and blood glucose level returned to normal, so that the medication became unnecessary. Histologically it was revealed that the tumor was a mixed adenoma consisting of adreno-medullary and cortical cells (corticomedullary adenoma). The literature on 21 cases of pheochromocytoma associated with Cushing's syndrome was briefly reviewed. Mathison (1969) reported the first case of a mixed tumor of adreno-medullary and cortical cells. So far as we know the present case is the second.
 ...
PMID:[A case of adrenal mixed tumor of pheochromocytoma and adrenocortical adenoma presenting diabetes mellitus and hypertension]. 837 53

Obese Zucker rats are hyperphagic, overweight, and infertile. It has been postulated that neuropeptide Y (NPY) overproduction may contribute to obesity and infertility in these animals. To test this hypothesis, ovariectomized, adult obese Zucker rats were implanted with cannulae in the third ventricle and subsequently injected with NPY antisera or normal rabbit sera (NRS) 6, 4 and 2 h before experimental observation. Steroid-treated females injected with NPY antisera were significantly more receptive and were more likely to show proceptive behaviors than after treatment with NRS (e.g., lordosis quotient: NPY antisera, 65.5+/-6.9%; NRS, 30.9+/-11.6%, P < 0.02; 91% displaying proceptivity after NPY antisera injection vs. 36% after NRS, P < 0.03). Injection of NPY antisera also curbed food intake and weight gain (24 h food intake: NPY antisera, 10.5+/-2.1 g; NRS, 20.5+/-1.7 g, P < 0.01; 24 h weight gain: NPY antisera, -5.4+/-2.2 g; NRS, 5.8+/-0.7 g, P < 0.01). Locomotor activity was similar after NRS and NPY antisera treatment (P > 0.5) suggesting that general malaise was not responsible for the effects of NPY antisera on food intake or body weight. These data suggest that endogenous neuropeptide Y contributes to excessive feeding and weight gain, and suppressed reproductive behaviors in obese Zucker female rats.
 ...
PMID:Intraventricular injection of neuropeptide Y antisera curbs weight gain and feeding, and increases the display of sexual behaviors in obese Zucker female rats. 980 26

Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant decrease in body mass. Behavioural analysis of drug-induced anorexia in animals demonstrates that various compounds profoundly effect feeding behaviour in differing ways. This indicates the variety of mechanisms by which pharmacological agents can induce changes in food intake, body weight and eventually body composition. Some of the same drugs produce decreases in food intake and weight loss in humans. Some of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). Such drugs can be considered as "appetite suppressants" with clinical potential as anti-obesity agents. Other drugs induce changes in food intake and body weight through various physiological mechanisms inducing feelings of nausea or even by side effect related malaise. Of the drugs considered suitable candidates for appetite suppressants are agents which act via peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), or alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin and Melanocortins) or levels of the key CNS appetite monoamine neurotransmitters such as serotonin (5-HT) and noradrenaline (NA). Recently, the hormone leptin has been regarded as a hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The peptide itself stimulates leptin receptors and it links with POMC and MC-4 receptors. These receptors may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i) psychological experience and behavioural expression of appetite, (ii) metabolism and peripheral physiology, and (iii) functioning of CNS neural pathways. In humans, modulation of appetite may involve changes in total caloric consumption, subjective changes in feelings of hunger and fullness, preferences for specific food items, and general macronutrient preferences. These may be expressed behaviourally as changes in meal patterns, snacking behaviour and food choice. Within the next 20 years it is certain that clinicians will have a new range of anti-obesity compounds available to choose from. Such novel compounds may act on a single component of the appetite system or target a combination of these components detailed in this review. Such compounds used in combination with lifestyle changes and dietary intervention may be useful in dealing with the rising world epidemic of obesity.
 ...
PMID:Pharmacology of appetite suppression. 1085 85

Alstrom syndrome is a rare autosomal recessive disorder associated with early childhood retinopathy, progressive sensorineural hearing loss, truncal obesity, and acanthosis nigricans. We report a 10-year-old boy with Alstrom syndrome presenting with general malaise and abnormal liver function for 1 year. In addition to the above mentioned features, he also had hyperglycemia and hyperinsulinemia. The mechanism responsible for the persistent elevation of liver enzymes could not be identified. To the best of our knowledge, this is the first-reported case of Alstrom syndrome with hepatic dysfunction in Taiwan.
 ...
PMID:Alstrom syndrome with hepatic dysfunction: report of one case. 1110 May 27


1 2 3 4 Next >>