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)

In patients more than 65-year-old with diabetes mellitus, positive late potentials on signal-averaged electrocardiograms were more common than in normal subjects (p < 0.05). This suggests that aged patients with diabetes mellitus are at risk for micromyocardial impairment. Myocardial scintigraphy with 123I-metaiodobenzylguanidine showed abnormally low uptake, in parallel with the data on SA-ECG. Thus, both methods may be clinically useful ways to noninvasively reveal micromyocardial impairment in aged patients with diabetes mellitus. Moreover, trimetazidine hydrochloride may be effective as therapy for micromyocardial impairment: the uptake of 123I-metaiodobenzyl guanidine had increased in some patients when measured 1 year after administration of trimetazidine hydrochloride (18 mg/day) and the late potential changed from positive to negative.
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PMID:[Cardiac impairment of elderly patients with diabetes mellitus as studied with non-invasive myocardial scintigraphy and signal-averaged electrocardiography]. 879 61

The aim of this study was to investigate the relationship between autonomic nerve dysfunction and myocardial uptake of 123I-meta-iodobenzyl guanidine (MIBG) in patients with diabetes mellitus. Twenty-two non-insulin-dependent diabetic patients, 9 with autonomic neuropathy [ANP(+)] and 13 without autonomic neuropathy [ANP(-)], and 8 controls were included in the study. Both planar and single photon emission tomographic (SPET) images were obtained 30 min (early) and 3 h (delayed) after the 123I-MIBG injection. The heart-to-mediastinal uptake ratio (H/M) and the washout ratio of 123I-MIBG (%WR) were calculated from planar images. The uptake ratio of the inferior wall to the anterior wall (I/ A) and the %WR of both the inferior and anterior walls were calculated from the SPET images. On the early plantar images, the mean H/M ratio in the ANP(+) group was significantly lower than that of the control group. The mean %WR on the planar images in the ANP(-) group was significantly higher than that of the controls. The SPET images demonstrated a reduction in MIBG uptake and significantly increased clearance in the inferior wall of the ANP(-) patients. These findings extended to other areas of the heart in the ANP(+) patients. In the quantitative analysis of the SPET images, the ANP(+) group had significantly lower I/A values and significantly higher %WR values in the anterior wall. The ANP(+) group showed significantly increased clearance of 123I-MIBG in the inferior wall. We conclude that 123I-MIBG myocardial scintigraphy is a useful diagnostic tool both in the early detection and evaluation of the progression of myocardial sympathetic nerve dysfunction in patients with diabetes mellitus. Both the I/A and %WR calculated from SPET images are useful parameters.
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PMID:123I-MIBG myocardial scintigraphy in diabetic patients: relationship to autonomic neuropathy. 884 23

Over a thousand combinations of polyanions and polycations were tested to search for new polymer candidates that would be suitable for encapsulation of living cells. The combination of sodium alginate, cellulose sulfate, poly (methylene-co-guanidine) hydrochloride, calcium chloride, and sodium chloride was most promising. In parallel, a novel multiloop chamber reactor was developed to control the time of complex formation and to negate gravitational effects such as pancreatic islet sedimentation and droplet deformation during the encapsulation process. Encapsulated rat islets demonstrated glucose-stimulated insulin secretion in vitro, and reversed diabetes in mice. This new capsule formulation and encapsulation system allows independent adjustments of capsule size, wall thickness, mechanical strength, and permeability, which may offer distinct advantages for immunoisolating cells.
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PMID:An encapsulation system for the immunoisolation of pancreatic islets. 909 38

Functional sequence changes in the promoter of a gene may have a direct effect on the rate of transcription and thus on cellular or plasma levels of the protein. For both the beta fibrinogen gene and the plasminogen activator inhibitor-1 (PAI-1) gene such functional variations have been described. For the fibrinogen gene a G/A sequence variation has been detected at position -455 of the promoter, with carriers of the A allele, representing roughly 20% of the population, consistently having 7-10% higher fibrinogen levels than those with the genotype G/G. For the PAI-1 gene we have detected a run of four or five Guanidine residues (4G/5G polymorphism), and in several published studies those homozygous for the 4G allele (25% of the population) having levels of PAI-1 roughly 30% higher levels than 5G5G individuals. The magnitude of both of these genotype effects indicates that they are likely to be of biological significance in causing an elevated risk of thrombosis and reduced fibrinolysis. However the magnitude of these effects are modulated by several environmental factors and data will be presented to demonstrate interaction between genotype and presence of ischaemic disease and physical exercise, in the determination of an individual's plasma fibrinogen levels and of triglycerides and diabetes in determining levels of PAI-1.
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PMID:Gene-environment interaction in the determination of levels of haemostatic variables involved in thrombosis and fibrinolysis. 919 96

Transplantation of immunoisolated islets of Langerhans has been proposed as a promising approach to treating insulin-dependent diabetes mellitus. Recently, a cell delivery system based on a multicomponent microcapsule has been designed for the immunoisolation of insulin-secreting pancreatic islets. The capsule, formed by polyelectrolyte complexation of sodium alginate and cellulose sulfate with poly(methylene-co-guanidine), markedly has improved mechanical strength compared with the widely used alginate/poly(L-lysine) capsules. It also provides a flexibility for readily adjusting membrane thickness and capsule size, and, more important, the membrane permeability can be altered over a wide range of molecular sizes. To rigorously test the capsule diffusion properties, we have improved capsule permeability measurement by using two complementary methods: (1) size exclusion chromatography with dextran standards; and (2) newly developed methodology for assessing permeability to a series of biologically relevant proteins. Viability and function of rat pancreatic islets enclosed in the capsules with different permeability were tested in vitro. The insulin secretion of encapsulated islets was well preserved even though slightly delayed in comparison with a control group of free islets. We believe that the unique features of this encapsulation system together with the precise characterization of its physical parameters will enable us to find the optimal range of capsule permeability for in vitro and in vivo survival and function of encapsulated pancreatic islets.
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PMID:Control and measurement of permeability for design of microcapsule cell delivery system. 942 97

Diabetic polyneuropathy is a complication, that affects most patients with longstanding diabetes mellitus, deteriorating their quality of life. In the last few years, new therapeutic approaches have been developed that can improve symptoms and neurologic function, and which may prevent and in some cases stop nerve damage, and even, promote nerve fiber regeneration. These treatments are supported by several investigations in animals and humans: a) thigh glycemic control (insulin), b) aldose reductase inhibition (tolrestat), c) prevention of protein glycation (amino-guanidine), d) improvement of nerve ischemia (vaso-dilators, gamma-linolenic acid), and e) administration of neurotrophic factors (gangliosides). Most evidence support the usefulness for glycemic control. Early treatment is suggested, because marked nerve fiber loss is present in advanced neuropathy.
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PMID:[Treatment of diabetic neuropathy]. 965

This work reflects the modern concepts of the pathogenesis of insulin-dependent diabetes mellitus and the prospective trends of pharmacological correction, analyzes the possibility of including in the therapeutic complex antiviral drugs, immunocorrecting measures, antioxidants, inhibitors of aldose reductase, amino guanidine, SH-group donors, and new medicamentous forms of insulin. Problems of an individual choice of drugs with consideration for the stage-development of the disease, the main pathogenetic mechanisms, the chronobiological rhythm of drug prescription, and adequate control of the efficacy of the applied pharmacotherapy are discussed.
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PMID:[The pathogenetic characteristics and the possible ways for the pharmacological correction of insulin-dependent diabetes mellitus]. 1043 53

This paper provides an overview of our current understanding of the role of sigma-receptors in the regulation of cough, gastrointestinal and retinal function. Systemic administration of N-(+)-allylnormetazocine ((+)SKF-10,047), 1,2-di-(2-toyl)guanidine (DTG) or pentazocine markedly reduced the number of coughs in a dose-dependent manner. The antitussive effect of these sigma-receptor ligands was significantly reduced by pretreatment with haloperidol or rimcazol, a specific antagonist of sigma-receptors. Antitussive effects of dextromethorphan and noscapine were significantly and dose-dependently reduced by pretreatment with rimcazole. However, rimcazole did not have a significant effect on the antitussive effect of morphine. These results suggest that haloperidol-sensitive sigma-receptors may be involved in the antitussive mechanism of non-narcotic antitussive drugs. Selective sigma-receptor ligands such as (+)SKF-10,047, DTG and (+)pentazocine elicit a potent protection against gastric and duodenal ulcers. Ulcerprotective activity of sigma-receptor ligands may be related to their stimulating effect on bicarbonate secretion through interaction with sigma-receptors in the gastrointestinal mucosa. Activation of sigma-receptors in retina protect retinal cells against glutamate-induced neurotoxicity. It is possible that sigma-receptor ligands may be useful as therapeutic drugs against retinal disease with ischemia-induced neuronal cell death such as retinal artery occlusion, diabetes mellitus or glaucoma.
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PMID:[Possible role of sigma-receptors in the regulation of cough reflex, gastrointestinal and retinal function]. 1056 63

Genetic evidence showed two non-Mendelian genetic elements of Saccharomyces cerevisiae, called [URE3] and [PSI], to be prions of Ure2p and Sup35p, respectively. [URE3] makes cells derepressed for nitrogen catabolism, while [PSI] elevates the efficiency of weak suppressor tRNAs. The same approach led to identification of the non-Mendelian element [Het-s] of the filamentous fungus Podospora anserina, as a prion of the het-s protein. The prion form of the het-s protein is required for heterokaryon incompatibility, a normal fungal function, suggesting that other normal cellular functions may be controlled by prions. [URE3] and [PSI] involve a self-propagating aggregation of Ure2p and Sup35p, respectively. In vitro, Ure2p and Sup35p form amyloid, a filamentous protein structure, high in beta-sheet with a characteristic green birefringent staining by the dye Congo Red. Amyloid deposits are a cardinal feature of Alzheimer's disease, non-insulin-dependent diabetes mellitus, the transmissible spongiform encephalopathies, and many other diseases. The prion domain of Ure2p consists of Asn-rich residues 1 to 80, but two nonoverlapping fragments of the molecule can, when overproduced, induce the de nova appearance of [URE3]. The prion domain of Sup35 consists of residues 1 to 114, also rich in Asn and Gln residues. While runs of Asn and Gln are important for [URE3] and [PSI], no such structures are found in PrP or the Het-s protein. Either elevated or depressed levels of the chaperone Hsp104 interfere with propagation of [PSI]. Both [URE3] and [PSI] are cured by growth of cells in millimolar guanidine HCl. [URE3] is also cured by overexpression of fragments of Ure2p or fusion proteins including parts of Ure2p.
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PMID:Prions in Saccharomyces and Podospora spp.: protein-based inheritance. 1058 68

Carnitine derivatives may have beneficial effects on cardiac and nerve function in patients with diabetes. The aim of this study was to investigate the effect of acetyl-L-carnitine (ALC) on myocardial sympathetic nervous function as measured with 123I-meta-iodobenzyl guanidine (MIBG) and single-photon emission tomography (SPET) in 19 patients with diabetes (placebo group, n = 6; ALC group, n = 13) at the beginning and at the end of a 1-year randomized, placebo-controlled, double-blind trial. The coefficient of variation for the MIBG analysis was 4%. In patients who were given a placebo, global myocardial MIBG uptake deteriorated during the study (MIBG uptake 1-year follow-up/baseline, 0.86 +/- 0.05, mean +/- standard error of mean), whereas in patients treated with ALC, MIBG uptake did not change significantly (1-year follow-up/baseline, 1.07 +/- 0.08; p = 0.03 between the groups). On the basis of these preliminary data, we conclude that long-term treatment with ALC may be of potential value in preventing the progressive loss of myocardial sympathetic nervous function in patients with diabetes. MIBG-SPET is a sensitive and thus valuable method in assessing the development of myocardial sympathetic nervous dysfunction.
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PMID:Long-term effect of acetyl-L-carnitine on myocardial 123I-MIBG uptake in patients with diabetes. 1075 Jun 38


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