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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.

Abstract: Adenosine monophosphate-activated protein kinase (AMPK) mediates metabolic responses of muscle to exercise and is involved in improvement of insulin resistance by endurance exercise. Recent studies have suggested that the renin-angiotensin system might negatively modulate insulin-mediated actions, but there has been little investigation of the correlation between the renin-angiotensin system and AMPK. To determine this correlation, we performed studies with glucose clamp in vivo, and glucose uptake by skeletal muscle ex vivo using 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). Six-week-old male Sprague-Dawley rats were fed standard chow (standard-diet rats; SD) or fructose-rich chow (fructose-fed rats; FFR) for 6 weeks. At the age of 12 weeks, SD and FFR were treated by oral gavage, either with angiotensin II (Ang II) receptor blockade (ARB; valsartan 30 mg/kg) or vehicle. Thirty minutes after the treatment, we performed glucose clamp studies to measure glucose infusion rates during infusion of insulin (GIRI) and of AICAR (GIRA), which stimulates AMPK, and studied the effect of ARB on either GIRI or GIRA. In an ex vivo study, we used bilateral fresh soleus muscles from 3-week-old male Sprague-Dawley rats to examine the glucose uptake (measured by 3H-2-deoxyglucose uptake) of one side of soleus muscle incubated with AICAR with or without Ang II, or with tumor necrosis factor-α, in comparison with that of the other (untreated control) side of the muscle. Blood pressure of FFR was significantly higher than that of SD rats. GIRI was significantly lower in FFR than in SD, and treatment with ARB did not change GIRI. GIRA of FFR was significantly lower than that of SD, but GIRA of FFR treated with ARB was significantly increased compared with that of FFR treated with vehicle. In the ex vivo study, incubation with AICAR significantly increased glucose uptake of soleus muscles, Ang II significantly decreased AICAR-activated glucose uptake in a dose-dependent manner, and ARB canceled the effect of Ang II. The results suggest that acute inhibition of the angiotensin 1 receptor improves glucose metabolism via not insulin but AMPK pathway through the angiotensin 1 receptor in FFR. [Copyright &y& Elsevier]

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]