In catabolic conditions, atrogin-1/MAFbx, a muscle-specific ubiquitin-ligase required for muscle atrophy, is increased, and concentrations of IGF-I, a growth factor known to have antiproteolytic action, are reduced. To define the relationship between the decline in IGF-I and the induction of atrogin-1/MAFbx, we studied the effect of IGF-I replacement on atrogin-1/MAFbx mRNA in rats fasted for 51 h and in rats made diabetic with streptozotocin (STZ). Fasting produced a 5.8-fold increase in atrogin-1/MAFbx (P < 0.001). This was attenuated to a 2.5-fold increase by injections of IGF-I (P < 0.05 vs. fasting). Animals with STZ-induced diabetes experienced a 15.1-fold increase in atrogin-1/MAFbx (P < 0.001). Normalization of their circulating IGF-I concentrations by IGF-I infusion blunted the induction of atrogin-1/MAFbx to 6.3-fold (P < 0.05 vs. STZ diabetes without IGF-I). To further delineate the regulation of atrogin-1/MAFbx by IGF-I, we studied a model of cultured muscle cells. We observed that IGF-I produced a time- and dose-dependent reduction of atrogin-1/MAFbx mRNA, with a 50% effective dose of 5 nm IGF-I, a physiological concentration. The degradation rate of atrogin-1/MAFbx mRNA was not affected by IGF-I, suggesting that the reduction of atrogin-1/MAFbx mRNA by IGF-I is a transcriptional effect. Exposure of muscle cells in culture to dexamethasone increased atrogin-1/MAFbx mRNA with a 50% effective dose of 10 nm, a pharmacological concentration. In the presence of dexamethasone, IGF-I at physiological concentrations retained its full inhibitory effect on atrogin-1/MAFbx mRNA. We conclude that IGF-I inhibits atrogin-1/MAFbx expression and speculate that this effect might contribute to the antiproteolytic action of IGF-I in muscle.

The role of TNF-alpha in muscle catabolism is well established, but little is known about the mechanisms of its catabolic action. One possibility could be that TNF-alpha impairs the production of local growth factors like IGF-I. The aim of this study was to investigate whether TNF-alpha can directly inhibit IGF-I gene and protein expression in muscle. First, we investigated whether the acute inflammation induced by endotoxin injection changes IGF-I and TNF-alpha mRNA in rat tibialis anterior muscle. Endotoxin rapidly increased TNF-alpha mRNA (7-fold at 1 h, P < 0.001) and later decreased IGF-I mRNA (-73% at 12 h, P < 0.001). Furthermore, in a model of C2C12 myotubes, TNF-alpha strongly inhibited IGF-I mRNA and protein (-73 and -47% after 72 h, P < 0.001 and P < 0.01, respectively). Other proinflammatory cytokines failed to inhibit IGF-I mRNA. The effect of TNF-alpha on IGF-I mRNA was not mediated by nitric oxide, and the activation of NF-kappaB was insufficient to inhibit IGF-I expression. Taken together, our data suggest that TNF-alpha induced in muscle after LPS injection can locally inhibit IGF-I expression. The inhibition of muscle IGF-I production could contribute to the catabolic effect of TNF-alpha.

The application of a barrier film creating a skin-protective polymer layer beneath transparent catheter dressings is associated with less dressing disruptions and skin integrity issues without altering the risk of infectious complications if used in combination with a chlorhexidine-impregnated catheter dressing.

Background: Microalbuminuria is often the first sign of renal involvement predicting overt nephropathy. For this reason, monitoring microalbuminuria and other risk factors associated with this condition is important to take measures to prevent or postpone overt nephropathy. This study aimed to investigate the prevalence of microalbuminuria in type 2 diabetes patients attending three diabetes centers in Tirana city. Patients and Methods: Two hundred and twenty patients with type 2 diabetes attending diabetes centers in Tirana were recruited in this crosssectional study. Medical records were used to collect data on duration of diabetes, waist circumference, history of hypertension, smoking. Blood samples were drawn after 12 h overnight fasting to measure glycosylated hemoglobin (HbA1c), serum cholesterol, triglyceride and creatinine. Microalbuminuria was assessed using dipstick kits in early morning urine samples. Results: The prevalence of normoalbuminuria was 58.3%, microalbuminuria 38.6% and macroalbuminuria 3.1%. Systolic and diastolic blood pressure (p < 0.01), HbA1c(p < 0.01) and fasting plasma glucose (p < 0.001) were significantly higher in microalbuminuric than in normoalbuminuric subjects. Multiple logistic regression analysis using microalbuminuria as the dependent variable in males shows that independent risk factors for diabetes patients with microalbuminuria were duration of diabetes, systolic blood pressure and waist circumference. We found that the OR for microalbuminuria became statistically significantly increased only at 16 years after the diagnosis of type 2 diabetes. At this time, 43.7% of patients had microalbuminuria. Conclusions: We found a high proportion of type 2 diabetes patients with microalbuminuria which raises implications for health policy inAlbania. This calls for early detection and good control of diabetes to reduce the burden of diabetic kidney disease in the future. Screening programs and optimized control of modifiable risk factors are needed to reduce the risk of diabetic nephropathy.

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