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The article presents a study on the occurrence of the impairment of Jak2-mediated protection in diabetic myocardium through the angiotensin II type 1 (AT1) receptor-mediated machanism in the U.S. The study intends to determine the capability of angiotensin II type 1 receptor to cause impairment of cardioprotective signaling in diabetic hearts. The findings reveal on the role of AT1 receptor mediated upregulation of calcinerium acitivity to diabetic heart's unresponsiveness to protection.

The article discusses a study to evaluate the factors that are responsible for creating burden among family caregivers of regular hemodialysis patients. Participants included 108 pairs of family caregivers and regular hemodialysis patients in Hokkaido Prefecture, Japan. The study concluded that caregivers tend to feel burdened by looking after patients for a long time as they spent a lot of time with their charges as well as paying a lot of money for their care.

Background: Hypokalemia is not a sensitive marker of primary aldosteronism (PA) , and method for screening PA by routine clinical parameters has not yet been established.Objective: We examined whether serum uric acid (UA) or urine pH alone, or their combination with serum K+ level is usable for PA screening .Design and Setting: Cross-sectional analyses were retrospectively performed on consecutive patients who visited a single general hospital from April 2012 to September 2013.Participants: Entry criteria were age <75 years old, hypertension and presence of data on serum aldosterone (ng/dL) and renin activity (ng/mL/hr). Exclusion criteria were use of aldosterone blockers, ACE inhibitors, angiotensin receptor antagonists, diuretics, beta-adrenergic blockers, steroids or UA-lowering drugs and diagnosis of secondary hypertensions other than PA.Main Outcome Measures: Diagnosis of PA was made in accordance with the guideline of Japanese Society of Hypertension: patients with aldosterone-to-renin activity ratio (ARR) > 20 and one or more positive results in captopril challenge test, furosemide-upright test, saline infusion test and/or ACTH stimulation test.Results: We enrolled 103 patients (PA = 29, essential hypertension [eHT] = 74). PA has lower serum K+ (3.5±0.32 vs 3.8±0.23 mEq/L, p<0.001, mean ± S.D.), higher urine pH (6.6±0.83 vs 6.1±0.62, p<0.001) and lower UA (5.6±1.6 vs 6.5±1.2 mg/dL, p=0.004) compared with those in eHT. Urine pH≧ 7.0 and UA < 6.0 mg/dL were selected as optimum cutoffs for diagnosis of PA by ROC curve analysis. Multivariable logistic regression analysis indicated that high urine pH, low UA and hypokalemia (K < 3.5 mEq/L) were independently associated with PA. Using the cutoff values, we developed a score system, PUK2 score, which is derived from the sum of point values of PA predictor; 1 point was assigned to low UA and to high urine pH and 2 points were assigned to hypokalemia. The prevalence of PA in the patients with PUK2 score of 0, 1, 2 and 3~ was 5.0%, 31%, 37%, and 83%,respectively. Furthermore, the likelihood ratio in patients with PUK2 score of 0 was 0.13 (95%CI: 0.034-0.52).Conclusions: PUK2 score is easy to use and useful for screening PA in hypertensive patients. [ABSTRACT FROM AUTHOR]

Insulin resistance is associated with hypertension, obesity, dyslipidemia, and type 2 diabetes. It is well known that tumor necrosis factor (TNF)-alpha is one of the factors linked to obesity-induced insulin resistance; however, there have been no reports on the role of TNF-alpha in insulin resistance in nonobese insulin-resistant hypertensives. We tested the hypothesis that TNF-alpha affects insulin resistance in nonobese insulin-resistant hypertensive fructose-fed rats (FFR) and that a TNF-alpha--converting enzyme (TACE) inhibitor that blocks TNF-alpha secretion improves insulin resistance in FFR. Six-week-old male Sprague-Dawley rats were fed either standard chow (control) or fructose-rich chow (FFR) for 6 weeks. For the last two weeks of a six-week period of either diet, the rats were treated with a vehicle (control or FFR) or a TACE inhibitor (100 mg/kg/d of KB-R7785; FFR+TACE-I) in peritoneal injection. At the age of 12 weeks, insulin sensitivity was assessed in all conscious rats by the euglycemic hyperinsulinemic glucose clamp technique. While FFR had higher blood pressure than the control rats (P<0.01), the TACE inhibitor did not change blood pressure. Insulin sensitivity (M-value) was reduced in FFR compared with that in the control rats (16.7 +/- 1.1 mg/kg per min and 10.3 +/- 0.6 mg/kg per min in the control rats and FFR, respectively, P<0.001), and the TACE inhibitor improved insulin sensitivity to the level of the control rats (14.3 +/- 1.2 mg/kg per min in FFR+TACE-I, P<0.01). These data indicate that TNF-alpha plays a major role in insulin resistance in nonobese insulin-resistant models and also suggest that TACE would be a good target for controlling insulin resistance not only in obese models but also in nonobese insulin-resistant models.