Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 72-year-old Hispanic man with diabetes presented with a 4-week history of a tender non-healing ulcer on the fifth digit of the left hand and a 3-day history of fever, chills, malaise, anorexia, and tender fluctuant nodules on the abdomen and left elbow. The patient, an avid gardener, was using prednisone and methotrexate for a debilitating seronegative polyarthropathy. A diagnosis of disseminated cutaneous sporotrichosis was made based on epidemiologic risk factors, clinical appearance, histopathologic examination, and a positive fungal culture. Use of prednisone was discontinued, the dosage of methotrexate was decreased, and use of oral itraconazole 400 mg/day was instituted. The patient's lesions cleared within 5 months, and no recurrence was noted during a 3-month follow-up. This case illustrates the typical association of the rare entity of disseminated cutaneous sporotrichosis with immunosuppression, an unusual lack of internal involvement, and a gratifying response to itraconazole.
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PMID:Disseminated cutaneous sporotrichosis treated with itraconazole. 1204 17

Five callitrichids (three common marmosets -Callithrix jacchus -, a black tufted-eared marmoset -C. penicillata-, and a saddle-back tamarin -Saguinus fuscicollis) were diagnosed with islet hyperplasia by histopathology and immunohistochemistry. All were privately-owned, unrelated callitrichids ranging from 2- to 4-year-old. Relevant findings were anorexia (3/5), vomiting (2/5), ptyalism (1/5), polyuria/polydipsia (1/5), respiratory distress (1/5), hyperglycemia (2/3) and glycosuria (1/1); hyperglycemia and glycosuria were associated with pregnancy in a common marmoset and resolved after reducing simple carbohydrates in diet. All five animals died, three of them after few premonitory signs; in two cases, other concurrent diseases unrelated to islet hyperplasia were considered the cause of death. Additional animals from two facilities had high weight (4), physical obesity (3), polyuria/polydipsia/polyphagia/uriposia (1), hyperglycemia (1), and/or glycosuria (2). Pathologic findings in the deceased callitrichids were: islet hyperplasia (5/5); hemosiderosis (5/5); lipomatosis (4/5) of several tissues (atria, 3/5; pancreas, gall bladder, intestine, esophagus, and thyroid, 2/5; liver, 1/5); pancreatic necrosis or steatonecrosis, and/or acute pancreatitis (3/5); and vacuolation of hepatocytes and renal tubular cells most likely consistent with hepatorenal lipidosis (2/5). The islets of Langerhans were more numerous and larger than in a control, and morphologically normal in all cases, except in a common marmoset that had a few cells with a foamy cytoplasm and shrunken hyperchromatic or picknotic nucleus. Insulin (5/5), glucagon (3/5), and somatostatin (3/5) immunohistochemistry revealed that most cells stained positively for insulin diffusely in their cytoplasm (5/5) (staining restricted to the vascular pole of b-cells in the control). These findings suggest that obesity, insulin resistance and/or type II diabetes may be implicated and thus a prospective study on these diseases in callitrichids is necessary to determine their etiopathogenesis.
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PMID:Islet hyperplasia in callitrichids. 1214 99

Leptin is the major regulator of body fat. It is a 16 kD protein released by fat cells into the blood and crosses the blood-brain barrier (BBB) to interact with its receptors at the arcuate nucleus to affect feeding, thermogenesis, and other functions. Within normal and obese body weight ranges, serum and cerebrospinal fluid (CSF) levels of leptin directly correlate with body mass index and adiposity. In animals, leptin at high levels exerts effects on appetite and at low levels informs the brain when fat reserves are adequate to switch behavioral, endocrine, and immune functions from starvation mode. Leptin offers a unique therapeutic opportunity for conditions related to body weight control, such as reversal of obesity and anorexia, and as an indirect treatment for diseases related to being over- or under-weight, such as insulin resistant diabetes and the endocrine changes accompanying starvation. In humans and in many rodent models, obesity may be a consequence of leptin resistance. More specifically, resistance likely results from an impaired transport of leptin across the BBB. Peripheral administration of native leptin results in weight reduction in moderately obese individuals and weight loss and reversal of insulin resistance and dyslipidemia in individuals with low leptin levels. The peripheral pharmacokinetic and BBB transport characteristics of native leptin suggests strategies for improving the therapeutic profile of leptin. These strategies include the development of longer lasting and more permeable analogs, development of antagonists, enhancing the activity of the leptin transporter, and delivering leptin by intrathecal administration.
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PMID:Strategies for the delivery of leptin to the CNS. 1216 78

Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be the critical site of action; however, a peripheral contribution cannot be ruled out. We compared doses of the FAS inhibitor C75 in the CNS (third ventricle [i3vt]) and periphery (intraperitoneal [IP]) to reduce food intake and body weight in rats. Centrally, the threshold dose was 3 micro g, whereas a dose of 10 mg/kg was required peripherally. Such data argue for FAS activity in the CNS as a potent target for the actions of C75. To control for nonspecific effects of FAS inhibition, we compared C75 administration in two models of illness, conditioned taste aversion and need-induced sodium appetite. Our results suggest the anorexia produced by IP C75 is accompanied by visceral illness, whereas the anorexia produced by i3vt is not. In addition, we placed animals in an indirect calorimeter after an IP injection of C75. We found that consistent with behavioral measures of visceral illness, peripheral C75 reduced heat expenditure and resulted in animals losing less weight than fasted control animals, suggesting that peripherally administered C75 has aversive properties. Understanding the mechanisms by which FAS inhibition in the CNS reduces food intake could lead to specific targets for the manipulation of energy balance and the treatment of obesity.
Diabetes 2002 Nov
PMID:Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion. 1240 10

The imaging findings in two miniature schnauzers with acute necrotizing pancreatitis are described. Both dogs were treated previously for diabetes mellitus and hyperlipidemia. Vomiting, anorexia, and lethargy were observed in both dogs at presentation. Laboratory evaluations supportive of pancreatitis included left shift, abnormally high serum amylase and lipase activities, hypocalcemia, and abnormally high serum activities of liver enzymes. Sonographically, both dogs had diffusely enlarged hypoechoic pancreatic tissue with anechoic foci compatible with necrosis, abscessation, phlegmon, and pseudocysts formation. Contrast-enhanced computed tomography (CT) findings in both dogs were compatible with pancreatic necrosis. Dog 1 was managed medically for 11 days. Follow-up CT scan in this dog disclosed decreased pancreatic size and increased contrast enhancement compatible with partial resolution of pancreatitis.
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PMID:Combined use of ultrasonography and contrast enhanced computed tomography to evaluate acute necrotizing pancreatitis in two dogs. 1262 55

Neuropeptide Y (NPY), the most abundant peptide present in the mammalian brain, exhibits a wide spectrum of central and peripheral activities mediated by at least six G-protein coupled receptors. The latter observation, and the implication of NPY in the pathophysiology of feeding, seizures, diabetes, intestinal dysfunction, cardiovascular diseases and respiratory disorders, have led to vigorous efforts to dissociate various effects of NPY and develop receptor selective ligands required for fundamental investigations, and possible clinical utility. These efforts have made significant advancement in the development of antagonists, especially for Y(1) and Y(5) receptors mediating NPY effects on feeding and/or thermogenesis. However, only a limited progress has been made in the case of Y(2) ligands, and none in the case of Y(4) ligands. Moreover, most of the nonpeptidic ligands developed to date have little use clinically because of their solubility and toxicity problems and their limited passage through blood-brain barrier. Furthermore, no progress has been made in developing lower molecular weight agonists, which may also have clinical potential in treating seizures, intestinal dysfunction, respiratory disorders, cachexia and anorexia. Thus, despite significant advances, NPY research is expected to attract scientists for years to come in the pursuit to develop clinically useful ligands. The recent advances in the peptide drug delivery techniques have given added impetus for these efforts. This article reviews the usefulness of widely used ligands as well as those developed more recently.
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PMID:Neuropeptide Y (NPY) family of hormones: progress in the development of receptor selective agonists and antagonists. 1276 44

A 54-year-old man was found to have hypertension at age 32, and a diagnosis of Werner's Syndrome was made at age 36 when he was examined for hyperlipidemia. Diabetes mellitus was found at age 42. Proteinuria appeared at age 49, and microscopic hematuria was seen at age 50. At age 51, serum creatinin level began to rise and atrophy of bilateral kidneys was observed by abdominal CT. There after, the renal function gradually worsened. At age 53, the serum creatinin level rose to 8.3 mg/dl, and systemic edema as well as loss of appetite appeared, resulting in the initiation of hemodialysis. In Werner's syndrome, though arteriosclerosis arises frequently, case reports with chronic renal failure are extremely rare. To investigate the cause of the renal dysfunction, renal biopsy was performed and the samples were histologically examined, revealing the presence of hypertensive glomerular changes. It is, thus, conceivable that hypertension had played a major role in the progression of renal failure in this case.
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PMID:[A report of a case with Werner's syndrome suffering from end-stage renal failure]. 1282 81

Phenethylbiguanide (DBI) was given to 70 unselected but not obese diabetic patients who were receiving restricted diabetic diets. The only side effects attributed to the drug were anorexia, nausea, vomiting and diarrhea in 28 patients. These symptoms subsided with reduction of dosage. No evidence of serious toxicity has been demonstrated in clinical and metabolic studies. In 27 of the 70 patients diabetes was controlled adequately with DBI alone, and more stable control was obtained in 11 labile diabetics who received DBI in combination with insulin.The mechanism of action is not definitely known.
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PMID:Phenethylbiguanide in diabetic patients; clinical and metabolic effects. 1363 34

A severaly retarded 30-year-old woman developed acute lithium intoxication. Since the age of 22, she had been treated with neuroleptics for her aggressive behavior. At 30 years of age, lithium carbonate was added to arrest self-injurious behavior, at an initial dosage of 300 mg/day and a maintenance dosage of 900 mg/day. She subsequently developed anorexia and weight loss, and was admitted to our hospital. After 7 months of lithium therapy, she suddenly had a high fever (38.3 degrees C), diabetes inspidus, severe hypernatremia, and became akinetic and mute. Under the suspicion of lithium intoxication, all medication was discontinued, and mannitol to increase renal lithium clearance. She was given gradually improved over a month, but remained hypothyroid. This case shows the importance of interaction of lithium carbonate and other drugs which may cause lithium intoxication. In patients with severe intellectual disabilities who are unable to complain their symptoms, lithium therapy requires particularly close attention to signs of early toxicity.
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PMID:[Lithium intoxication in a patient with severe motor and intellectual disabilities]. 1367 53

The antihypertensive effect of the diuretic benzothiadiazines has been attributed to salt depletion and the resultant reduction in plasma volume. The study described in this report was concerned with the effects of diazoxide, a non-diuretic analogue which had been found in animal experiments to have a hypotensive effect.Intravenous diazoxide (3 mg./kg.) reduced blood pressure an average of 26/16 mm. Hg in seven hypertensive subjects. An associated rise in cardiac output (0.7 to 5.7 1./min.) and decrease in peripheral vascular resistance occurred. There was no postural hypotension, or change in external salt balance or in the concentration of serum sodium or potassium.Oral administration of the drug (0.2 to 0.5 g./day for eight to 50 weeks) lowered blood pressure more than 15/10 mm. Hg in 26 of 30 hypertensive subjects. Associated effects were: (1) weight gain in 26 of 30 subjects, (2) anorexia in 15 of 30, (3) lacrimation in six of 30, (4) aggravation of diabetes in two, and (5) transient cardiac arrhythmias in four. This study suggests that this benzothiadiazine acts directly on arterioles to reduce peripheral vascular resistance.
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PMID:Clinical observations on an antihypertensive chlorothiazide analogue devoid of diuretic activity. 1398 Dec 25


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