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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cutaneous fungal infections in immunocompromised patients can be aggressive and difficult to treat. To determine the safety and efficacy of oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with human immunodeficiency virus (HIV) infection or diabetes, 2 prospective, randomized, open-label studies were conducted in general community and referral centers. HIV-positive (n = 6) and diabetic patients (n = 8) between the ages of 18 and 75 years diagnosed with either tinea corporis or tinea cruris, as confirmed by potassium hydroxide (KOH) wet mount microscopy, were randomized to receive either 1 or 2 weeks of the antifungal treatment. Patients received oral terbinafine 250 mg once daily for 1 or 2 weeks. Main outcome measures were mycological cure, determined at week 6 for HIV-positive and diabetic patients. Three subjects were excluded from the efficacy analyses because of negative cultures at screening (n = 2) and lack of follow-up cultures (n = 1). Efficacy results were similar between the 1- and 2-week groups in both studies. All HIV-positive subjects and 83% of diabetic subjects achieved mycological cures at week 6 based on culture results. In a safety population that included all randomized patients (N = 14), no subject experienced adverse events or significant changes in laboratory findings related to study medication. Results of these small series indicate that a short course of oral terbinafine 250 mg once daily is a safe and effective treatment for tinea corporis or tinea cruris in subjects with HIV infection or diabetes.
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PMID:Safety and efficacy of short-duration oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with HIV infection or diabetes. 1149 30

Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1+/-17.5 vs 63.2+/-14.9 mg 100 g(-1) min(-1), P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28+/-0.35; controls, 1.55+/-0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81+/-17 ml 100 g(-1) min(-1); saline, 75+/-19 ml 100 g(-1) min(-1), P=NS) or MVR (deferoxamine, 1.0+/-0.5 mmHg ml(-1) 100 g(-1) min(-1); saline, 1.2+/-0.6 mmHg ml(-1) 100 g(-1) min(-1), P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary microvasculature to sympathetic stimulation. Hydroxyl radicals may play a role in the pathogenesis of flow abnormalities in type 1 diabetes.
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PMID:Deferoxamine improves coronary vascular responses to sympathetic stimulation in patients with type 1 diabetes mellitus. 1211 Nov 29

The increasing prevalence of type 2 diabetes is a major problem for healthcare providers globally, since it is associated with serious microvascular and macrovascular complications. Although microvascular complications can be largely reduced with strict glycemic control, prevention of macrovascular disease involves a multifaceted approach that addresses all major risk factors, including dyslipidemia, hypertension, and insulin insensitivity. In particular, the treatment of diabetic dyslipidemia is a major challenge for diabetologists and cardiologists, as it is characterized by an array of lipid abnormalities. The management of diabetic dyslipidemia should initially include lifestyle approaches such as improved nutrition and weight reduction; however, the majority of patients require the addition of pharmacotherapy. Whilst insulin and/or oral hypoglycemic drugs are generally prescribed for the treatment of hyperglycemia, the addition of lipid-lowering drugs may be necessary for the control of diabetic dyslipidemia. The American Diabetes Association guidelines recommend lowering of low-density lipoprotein cholesterol (LDL-C) as a first priority. Hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) are recommended for first-line therapy in diabetic patients, since these agents are effective at reducing LDL-C levels. Whilst statins provide effective control of dyslipidemia in the majority of patients, more efficacious treatment regimens would provide greater benefit to more patients. Combination therapies may provide one solution to obtaining maximal lipid profile modifications, although the introduction of new, more efficacious agents for use as monotherapy may provide a more acceptable option, as drug combinations are often associated with poor tolerability and patient compliance.
Diabetes Metab Res Rev
PMID:Statin therapy for the treatment of diabetic dyslipidemia. 1287 5

Hepatitis B vaccines (HBVs) are composed of highly purified preparations of hepatitis B virus surface antigen (HBsAg). An adjuvant, either aluminium phosphate or aluminium hydroxide, is added to the vaccines, which are sometimes preserved with thiomersal. In placebo-controlled studies, common side effects other than local reactions were reported no more frequently among vaccine recipients than among individuals receiving a placebo. A number of controversial adverse events have, however, been purported to be associated with HBVs, including rheumatoid arthritis (RA), diabetes, demyelinating diseases (e.g., multiple sclerosis [MS]), chronic fatigue syndrome, and more recently, lymphoblastic leukaemia. In addition, the safety of the thiomersal and aluminium contained in the vaccine has also been under close scrutiny. These issues have been reviewed by a number of country-specific or international independent review committees such as that of the US Institute of Medicine (IOM) and the World Health Organization's (WHO) Global Advisory Committee on Vaccine Safety (GACVS). Upon review of the scientific evidence, none of the serious allegations have so far been confirmed. On the contrary, scientific evidence has accumulated to disprove many of the allegations. In particular, the IOM committee has concluded that the evidence favoured rejection of a causal relationship between HBV administered to adults and incident MS or MS relapse. Whilst it is important to continue monitoring some of the safety issues, there is no evidence to suggest that the WHO should consider altering its recommendation that all countries should have universal infant and/or adolescent immunisation programmes. The risks of hepatitis B vaccination are only theoretical in comparison with clear benefits in terms of cirrhosis and cancer prevention, and the HBV remains one with an excellent safety profile.
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PMID:Safety of immunisation and adverse events following vaccination against hepatitis B. 1290 2

Onychomycosis is the most common nail disorder in adults. Predisposing factors are immunosuppression, poor peripheral circulation, diabetes mellitus, increasing age, nail trauma, and tinea pedis. Autoimmune patients, who carry many of these predisposing factors, have never been studied. Autoimmune patients, with underlying autoimmune skin diseases; pemphigus, systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, dermatomyositis and cutaneous vasculitis, as well as having abnormal-appearing nail(s) with suspicion of fungal nail infection were included. Clinical information was obtained. The causative organisms were identified by potassium hydroxide preparation and cultured. Duration of onychomycosis in autoimmune patients was twice longer than in non-autoimmune patients. Of those with mycological proven onychomycosis, the autoimmune patients had significantly more affected nails (p < 0.05; chi2, two-sided) compared to the non-autoimmune patients but there was no difference in the affected fingernails or toenails and clinical type of onychomycosis. Candida spp was the most frequently found in autoimmune subjects compared to dermatophytes, Trichophyton rubrum. However, dermatophytes especially Trichophyton rubrum was the most common causative organism in non-autoimmune samples, followed by Candida spp. The causative organisms were more frequently discovered in autoimmune patients, whether by potassium hydroxide (KOH) or culture, than in non-autoimmune patients (p < 0.05; chi2, two-sided).
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PMID:Clinical characteristics and mycology of onychomycosis in autoimmune patients. 1469 80

Hormones play a modulating role in allergic inflammation. An inverse relationship between atopy and diabetes mellitus was reported. The mechanisms regulating this interaction are not completely understood. This study examined whether insulin influences mast cell activation following antigen challenge in rats. The experimental design included alloxan-induced diabetic rats and matching controls. Experiments were performed 30 days after alloxan injection. The animals were sensitised by s.c. injection of ovalbumin (OA) and aluminium hydroxide. OA-induced airway contraction, morphometric analysis of airway mast cells and tissue histamine quantification were evaluated in the isolated main bronchus and intrapulmonary bronchus upon exposure to antigen in vitro. Relative to controls, a reduced contraction to OA was observed in bronchial segments isolated from diabetic rats. This was accompanied by a 50% reduction in the number of degranulated mast cells and in histamine release. A complete recovery of the impaired responses was observed under the influence of insulin. In conclusion, the data suggested that insulin might modulate the controlling of mast cell degranulation; therefore, the early-phase response to antigen provocation, which represents a new insight into a better understanding of the mechanisms, accounted for the decreased risk of asthma among type-1 diabetic patients.
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PMID:Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin. 1545 32

Mycological analysis of swabs and scraping samples from the external ear canals of 40 patients with clinically diagnosed otomycosis (10 neonates, 30 adults) revealed the presence of fungi as etiological agents. They were investigated microscopically using 20 % potassium hydroxide, and by cultivation on Sabouraud's glucose agar. The Candida species were identified using the germ-tube test, micromorphology observations of colonies on rice agar, and particularly by the commercial kit AUXAcolor. The following Candida species were identified in the aural material examined: C. albicans (n = 21; 52.5 %), C. parapsilosis (11; 27.5), C. tropicalis (3; 7.5), C. krusei (3; 7.5), C. guilliermondii (2; 5.0). The above yeasts were present in samples together with Staphylococcus epidermidis (31), S. aureus (16), alpha-hemolytic streptococci (14), Neisseria spp. (14), Proteus mirabilis (3), Pseudomonas aeruginosa (3), Escherichia coli (1) and Haemophilus influenzae (1). The most frequent predisposing factors for otomycosis were swimming in public pools and/or bath, spa and diabetes mellitus.
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PMID:Otomycoses of candidal origin in eastern Slovakia. 1570 53

Vildagliptin (NVP-LAF237/(2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile) was described as a potent, selective and orally bio-available dipeptidyl-peptidase IV (DPP IV, EC 3.4.14.5) inhibitor [Villhauer EB, Brinkman JA, Naderi GB, Burkey BF, Dunning BE, Prasad K, et al.1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003;46:2774-89]. Phase III clinical trials for the use of this compound in the treatment of Type 2 diabetes were started in the first quarter of 2004. In this paper, we report on (1) the kinetics of binding, (2) the type of inhibition, (3) the selectivity with respect to other peptidases, and (4) the inhibitory potency on the DPP IV catalyzed degradation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and substance P. Vildagliptin behaved as a slow-binding DPP IV inhibitor with an association rate constant of 1.4x10(5)M(-1)s(-1) and a K(i) of 17nM. It is a micromolar inhibitor for dipeptidyl-peptidase 8 and does not significantly inhibit dipeptidyl-peptidase II (EC 3.4.11.2), prolyl oligopeptidase (EC 3.4.21.26), aminopeptidase P (EC 3.4.11.9) or aminopeptidase M (EC 3.4.11.2). There was no evidence for substrate specific inhibition of DPP IV by Vildagliptin or for important allosteric factors affecting the inhibition constant in presence of GIP and GLP-1.
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PMID:Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile). 1590 7

Many dipeptide boronic acids of the type H(2)N-X-Y-B(OH)(2) are potent protease inhibitors. Interest in these compounds as drugs for cancer, diabetes, and other diseases is growing. Because of the great mutual B-N affinity, cyclization through the N- and B-termini, forming six-membered rings, is a common occurrence at neutral pH and higher where the terminal amino group is unprotonated. Here we report the discovery that when X, the N-terminal amino acid, contains a side chain having a functional group with boron affinity and suitable geometry, additional cyclization in the form of bidentate intramolecular chelation or "autochelation" may occur, predominantly at mid pH. NMR studies of two compounds, l-Aspartyl-l-boroProline (Asp-boroPro) and l-Histidyl-l-boroProline (His-boroPro), are reported here from pH 0.5 to pH 12 by (1)H, (15)N, (13)C, and (11)B NMR. Both of these previously unreported autochelates contain two fused six-membered rings, cis-proline, chiral boron, and -NH(2)(+) protons in slow exchange with water, even at 25 degrees C and pH as high as 4. Using microscopic acid-base equilibrium constants, we show that at high pH (>8 for Asp-boroPro and >10 for His-boroPro) hydroxide competes with the side chains for boron, reducing the chelates from bidentate to monodentate. At low pH (<0.5), proton competition for N-terminal nitrogens causes both compounds to become noncyclic. High chelate stability causes a reduction of the apparent acidic dissociation constant of the protonated N-terminal amino group greater than eight units. In the His-boroPro autochelate, imidazolate anion is produced at the extraordinarily low pH value of approximately 9.
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PMID:Autochelation in dipeptide boronic acids: pH-dependent structures and equilibria of Asp-boroPro and His-boroPro by NMR spectroscopy. 1592 38

[Reaction: see text]. Asymmetric glycolate alkylation using a protected acetophenone surrogate under solid-liquid phase-transfer conditions is a new approach to the synthesis of 2-hydroxy esters and acids. Diphenylmethyloxy-2,5-dimethoxyacetophenone 1 with a trifluorobenzyl cinchonidinium bromide catalyst 9 (10 mol %) and cesium hydroxide provided S-alkylation products 2 at -35 degrees C in high yield (80-99%) and with excellent enantioselectivities using a wide range of electrophiles (80-90% ee). Alkylated products were elaborated to useful alpha-hydroxy intermediates 3 using bis-TMS peroxide Baeyer-Villiger conditions and selective transesterification reactions. The ester products have been enantioenriched by simple recrystallization from ether to give a single isomer (99% ee). A tight ion-pair model is proposed for the observed S-stereoinduction that includes van der Waals contacts between the extended enolate and the isoquinoline of the catalyst. To demonstrate the utility of the new methodology, the anti-diabetes drug (-)-ragaglitazar 24 was synthesized in six steps from a key 2-alkoxy-3-p-phenoxypropionic acid 26 that was made using PTC glycolate alkylation.
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PMID:Asymmetric phase-transfer catalyzed glycolate alkylation, investigation of the scope, and application to the synthesis of (-)-ragaglitazar. 1626 22


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