Acute Exercise Increases Plasma Levels of Muscle-Derived Microvesicles Carrying Fatty Acid Transport Proteins.

CONTEXT: Microvesicles (MVs) are a class of membrane particles shed by any cell in the body in physiological and pathological conditions. They are considered to be key players in intercellular communication, and with a molecular content reflecting the composition of the cell of origin, they have recently emerged as a promising source of biomarkers in a number of diseases. OBJECTIVE: The effects of acute exercise on the plasma concentration of skeletal muscle-derived MVs (SkMVs) carrying metabolically important membrane proteins were examined. PARTICIPANTS: Thirteen men with obesity and type 2 diabetes mellitus (T2DM) and 14 healthy male controls with obesity exercised on a cycle ergometer for 60 minutes. INTERVENTIONS: Muscle biopsies and blood samples-obtained before exercise, immediately after exercise, and 3 hours into recovery-were collected for the analysis of long-chain fatty acid (LCFA) transport proteins CD36 (a scavenger receptor class B protein) and fatty acid transport protein 4 (FATP4) mRNA content in muscle and for flow cytometric studies on circulating SkMVs carrying either LCFA transport protein. RESULTS: Besides establishing a flow cytometric approach for the detection of circulating SkMVs and subpopulations carrying either CD36 or FATP4 and thereby adding proof to their existence, we demonstrated an overall exercise-induced change of SkMVs carrying these LCFA transport proteins. A positive correlation between exercise-induced changes in skeletal muscle CD36 mRNA expression and concentrations of SkMVs carrying CD36 was found in T2DM only. CONCLUSIONS: This approach could add important real-time information about the abundance of LCFA transport proteins present on activated muscle cells in subjects with impaired glucose metabolism.

The heterozygous N291S mutation in the lipoprotein lipase gene impairs whole-body insulin sensitivity and affects a distinct set of plasma metabolites in humans.

BACKGROUND: Mutations in the lipoprotein lipase gene causing decreased lipoprotein lipase activity are associated with surrogate markers of insulin resistance and the metabolic syndrome in humans. OBJECTIVE: We investigated the hypothesis that a heterozygous lipoprotein lipase mutation (N291S) induces whole-body insulin resistance and alterations in the plasma metabolome. METHODS: In 6 carriers of a heterozygous lipoprotein lipase mutation (N291S) and 11 age-matched and weight-matched healthy controls, we examined insulin sensitivity and substrate metabolism by euglycemic-hyperinsulinemic clamps combined with indirect calorimetry. Plasma samples were taken before and after the clamp (4 hours of physiological hyperinsulinemia), and metabolites were measured enzymatically or by gas chromatography-mass spectrometry. RESULTS: Compared with healthy controls, heterozygous carriers of a defective lipoprotein lipase allele had elevated fasting plasma levels triglycerides (P < .006), and markedly impaired insulin-stimulated glucose disposal rates (P < .024) and nonoxidative glucose metabolism (P < .015). Plasma metabolite profiling demonstrated lower circulating levels of pyruvic acid and α-tocopherol in the N291S carriers than in controls both before and after stimulation with insulin (all >1.5-fold change and P < .05). CONCLUSION: Heterozygous carriers with a defective lipoprotein lipase allele are less insulin sensitive and have increased plasma levels of nonesterified fatty acids and triglycerides. The heterozygous N291S carriers also have a distinct plasma metabolomic signature, which may serve as a diagnostic tool for deficient lipoprotein lipase activity and as a marker of lipid-induced insulin resistance.

Topical Antimycotics for Oral Candidiasis in Warfarin Users.

Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis.

[Anemia--prevalence and etiology among acutely admitted geriatric patients]. / Anaemi--praevalens og aetiologi hos patienter indlagt på en geriatrisk afdeling.

INTRODUCTION: The purpose of this study was to determine the prevalence of anemia among acutely admitted geriatric patients, and among these patients to ascertain how often anemia is listed as a diagnosis, the distribution of these diagnoses and to compare the diagnostic approach to anemia with that suggested in the literature. MATERIALS AND METHODS: Age, sex and hemoglobin concentrations (hgb) were registered for patients referred to the acute geriatric ward of Odense University Hospital between 6/1/04 and 8/31/04. The prevalence of anemia was determined on the basis of the local laboratory's sex-specific lower reference limits for hgb. Diagnoses of discharge, laboratory data and, if performed, results of bone marrow and endoscopic investigations were also registered for anemic patients. RESULTS: 110 of 289 patients (38%) were anemic. The prevalence was significantly higher among men (61%, 95% confidence interval 51-71%) than among women (27%, 95% confidence interval 21-34%). 30 of the anemic patients (27%) had anemia listed as a diagnosis, including 14 with the diagnosis anemia without specification. A minority of anemic patients had measurements of serum ferritin (37%), serum iron (10%), plasma cobalamin (35%) and erythrocyte folate (35%), and a blood smear was likewise performed on a minority of anemic patients (26%). CONCLUSION: Anemia often remains undiagnosed or ignored. Clinicians should be aware of the high prevalence of anemia among geriatric patients and should appreciate the importance of a correct diagnostic approach to anemia in the elderly.