The oxygen therapy.

Oxygen (O(2)) is a vital element. Shortage of O(2) results in deranged metabolism and important changes in vascular tone with opposite effects on the systemic and pulmonary circulation. During hypoxemia, oxidative stress exposes the organism to a sort of accelerated senescence as well as to several acute untoward effects. Thus, hypoxemia should be promptly recognized and treated, hopefully by measures tailored to the pathophysiological mechanisms underlying hypoxemia. However, O(2) therapy remains the most common therapy of hypoxemia, but it must be carefully tailored to relieve hypoxemia without provoking hyperoxia or hypercarbia. Then, the individual response to O(2) as well as changing needs of O(2) during sleep or exercise must be evaluated to provide the best O(2) therapy. Hyperoxia, the effect of overcorrection of hypoxia, can dramatically impact the health status and threaten the survival of the newborn and, through different mechanisms and effects, the adult. A thorough knowledge of the pathophysiological bases of hypoxemia and O(2) storage and delivery devices is then mandatory to administer O(2) therapy guaranteeing for optimal correction of hypoxemia and minimizing the risk of hyperoxia. Consistent with this aim also is a careful scrutiny of instruments and procedures for monitoring the individual response to O(2) over time. Thus, at variance from classical pharmacological therapy, performing O(2) therapy requires a vast array of clinical and technical competences. The optimal integration of these competences is needed to optimize O(2) therapy on individual bases.

Endothelial dysfunction and non-alcoholic liver steatosis in hypertensive patients.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease, characterized by insulin resistance, has been correlated with several clinical and pathological manifestations, such as intima-media thickness. At present, no data are available regarding endothelial dysfunction, the first step in atherosclerosis, and non-alcoholic fatty liver disease. The aim of this study was to test a possible association between non-alcoholic fatty liver disease and endothelium-dependent vasodilation in a group of hypertensive patients. METHODS AND RESULTS: A total of 40 never-treated uncomplicated hypertensive outpatients were enrolled. Patients underwent a complete clinical and biochemical work-up including ultrasonographic scanning to detect liver steatosis. Insulin sensitivity was estimated by using the homeostasis model assessment (HOMA) index. Endothelial function was assessed by strain-gauge plethysmography during intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside. Endothelium-dependent vasodilation was significantly reduced in hypertensive patients with liver steatosis in comparison with those without. Statistical analysis demonstrated that the HOMA index was the strongest predictor of both endothelium-dependent vasodilation and liver steatosis. In particular, one point of HOMA accounts for 37.9% of forearm blood flow variation, and increases the risk of liver steatosis by 86.4%. CONCLUSION: Our data demonstrate that hypertensive patients with liver steatosis have a reduced endothelium-dependent vasodilation and highest insulin resistance. In keeping with this, it is possible to hypothesize that liver steatosis may be considered a marker of vascular damage in essential hypertension.

IGF-1 levels link estimated glomerular filtration rate to insulin resistance in obesity: a study in obese, but metabolically healthy, subjects and obese, insulin-resistant subjects.

BACKGROUND AND AIMS: Metabolically healthy but obese (MHO) subjects have a favourable cardio-metabolic risk profile, but whether they are also at lower risk for kidney dysfunction is still questionable. METHODS AND RESULTS: A total of 106 MHO, 122 normal-weight and 212 insulin-resistant obese (IRO) subjects were stratified on the basis of their insulin sensitivity and body mass index (BMI). The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR) and ISI index was used to estimate insulin sensitivity. eGFR was significantly lower in IRO as compared to MHO subjects after adjusting for age, gender and BMI (P = 0.008). In a logistic regression model adjusted for age, gender and BMI, IRO subjects showed an increased risk of having eGFR in the lowest quartile (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.01-3.58; P = 0.04) as compared with MHO subjects. This association was maintained when waist, lean body mass, blood pressure, HDL cholesterol, triglyceride, fasting glucose and insulin levels were additionally included into the model (OR 2.49, 95%CI 1.17-5.27; P = 0.01), but its independence was not retained with further inclusion of insulin-like growth factor-1 (IGF-1) levels (OR 2.16, 95%CI 0.93-5.04; P = 0.07) No differences in eGFR were observed between non-obese and MHO individuals. CONCLUSIONS: These results indicate that heterogeneity in obese phenotypes may account for conflicting evidence regarding the significance of obesity as a risk factor for chronic kidney disease. Our findings suggest that obesity is associated with lower kidney function only when insulin sensitivity is reduced, and that plasma IGF-1 is likely to be an important mechanism linking the IRO phenotype with reduced eGFR.