Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
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Exp. Clin. Endocrinol. Diabetes · Jan 2000
Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome and in patients with adrenal incidentaloma.
It is known that either chronic glucocorticoid administration or endogenous hypercortisolism frequently induce an hypercoagulable condition. Since little is known about the evaluation of markers of haemostatic and fibrinolytic systems in other adrenal disorders, we studied plasminogen activator inhibitor (PAI-1), tissue-plasminogen activator (t-PA), fibrinogen and von Willebrand factor antigen (vWF-Ag) levels in 11 patients with Cushing's syndrome and in 12 patients with adrenal incidentaloma. In patients with Cushing's syndrome mean PAI-1, t-PA and vWF-Ag levels did not significantly differ from those found in 50 age- and sex-matched controls, while mean fibrinogen levels were significantly higher in patients (337.0+/-39.1 mg/dl) than in normal subjects (278.9+/-8.4 mg/dl). ⋯ An increased t-PA level was occasionally observed only in the patient with adrenal carcinoma. On the whole, an alteration of at least one of haemostatic and fibrinolytic parameters was detected in 55% of the patients with Cushing's syndrome and in 42% of those with adrenal incidentaloma. In conclusion, early alterations of coagulation and fibrinolytic systems may be found in some patients with adrenal disorders, thus suggesting the opportunity of an accurate follow-up in order to identify possible risk factors for cardiovascular disease and thromboembolism.
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Exp. Clin. Endocrinol. Diabetes · Jan 1999
ReviewAlpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials.
Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Near-normoglycaemia is now generally accepted as the primary approach to prevention of diabetic neuropathy, but is not achievable in a considerable number of patients. In the past two decades several medical treatments that exert their effects despite hyperglycaemia have been derived from the experimental pathogenetic concepts of diabetic neuropathy. ⋯ The following conclusions can be drawn from the recent controlled clinical trials. 1.) Short-term treatment for 3 weeks using 600 mg of thioctic acid i.v. per day appears to reduce the chief symptoms of diabetic polyneuropathy. A 3-week pilot study of 1800 mg per day given orally indicates that the therapeutic effect may be independent of the route of administration, but this needs to be confirmed in a larger sample size. 2.) The effect on symptoms is accompanied by an improvement of neuropathic deficits. 3.) Oral treatment for 4-7 months tends to reduce neuropathic deficits and improves cardiac autonomic neuropathy. 4.) Preliminary data over 2 years indicate possible long-term improvement in motor and sensory nerve conduction in the lower limbs. 5.) Clinical and postmarketing surveillance studies have revealed a highly favourable safety profile of the drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with thioctic acid (NATHAN I Study) is being conducted in North America and Europe aimed at slowing the progression of diabetic polyneuropathy using a clinically meaningful and reliable primary outcome measure that combines clinical and neurophysiological assessment.
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Exp. Clin. Endocrinol. Diabetes · Jan 1999
Immunoprecipitation analysis of pathological autoantibodies in Graves' patients' sera using biotinylated human thyrotropin receptor labeled with 125I-neutravidiny.
In the present article we describe a method for the direct immunoprecipitation analysis of pathological autoantibodies against TSH receptor (TSHR) in sera of patients with Graves' disease. For this purpose the fusion TSH receptor (TSHR-BIO-6HIS) was constructed. This fusion consists of the N-terminal 725 amino acids of the human TSHR linked to the 87-amino acid C-terminal domain of the biotin carboxyl carrier protein subunit of E. coli acetyl-CoA carboxylase (this domain directs the efficient posttranslational biotinylation of the protein) followed by 6 histidine sequence. ⋯ The 125I-neutravidin labeled TSHR-BIO-6HIS, freed of the excess of nonbound radioactivity, was eluted from Ni-NTA agarose and used for the detection of pathological autoantibodies in 50 Graves' disease, 10 Hashimoto's disease, 10 insulin-dependent diabetes mellitus and 50 normal sera. 46 of 50 (92%) Graves' disease sera were positive in immunoprecipitation assay, as they have bound 125I-TSHR more effectively than the normal sera. There was a clear positive correlation between the immunoprecipitating activity and TSH-binding inhibiting activity of different Graves' sera (r = 0.69, P < 0.001). These findings pave the way for the development of a new practical assay, capable of detecting all pathological autoantibodies to the TSHR, particularly those which bind but do not affect the hormone-receptor interaction.
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Exp. Clin. Endocrinol. Diabetes · Jan 1998
ReviewTo be lean or not to be lean. Is leptin the answer?
Leptin and the leptin receptor genes have been identified as the site of mutations in the peripheral adipocyte hormone pathway responsible for obesity in the ob/ob mouse (Zhang et al., 1994) and the db/db mouse (Chen et al., 1996). In obese humans, ob/ob like mutations in leptin are rare but confirm a role for leptin (Montague et al., 1997), and db/db like mutations in the leptin receptor have not been found (Considine et al., 1996a); however, the increased understanding of the molecular basis for obesity has generated tremendous interest among scientists and patients alike. The new knowledge could be the base for intelligent drugs for the treatment of obesity. Herein we will put in perspective a) the physiological background that led to the discovery of leptin, b) leptin biosynthesis, c) leptin action and d) the clinical issues related to leptin as a drug for the treatment of obesity.