Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
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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.