Clinical relevance of gallbladder wall thickening for dengue severity: A cross-sectional study.

Dengue fever is the most important arthropod-borne viral infection worldwide. Secondary prevention to reduce mortality through improved clinical case management has substantially lowered the mortality rate for severe dengue during the past two decades. Gallbladder wall thickening (GBWT) is a nonspecific finding often associated with more severe cases of dengue infection. This study had the aim to describe the ultrasonographic findings in hospitalized patients with dengue infection from Manaus (in the Western Brazilian Amazon) and to correlate the GBWT with dengue severity, symptoms and laboratorial analysis. Patients from 13-84 years admitted to the emergency department at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) were enrolled in this study. Patients' selection occurred during the most recent and huge dengue outbreak within the first semester of 2011. All enrolled subjects were systematically tested in order to rule out other possible etiologies for gallbladder inflammation. Abdominal ultrasound was performed by a single physician through bedside portable equipment and all other clinical and laboratorial information were retrieved from patients' electronic files. 54 subjects were considered for analysis, with confirmed dengue infection by NS1 and/or RT-PCR positivity. From all enrolled patients, 50 (42.4%) presented GBWT. GBWT was significantly and independently related to: age under 31 years, pregnancy, presence of bleeding, presence of any cavitary effusion, DHF classification and severe dengue classifications. During dengue outbreaks, the GBWT identification through a non-invasive and bedside procedure is a confident marker for prompt recognition of potential severe cases.

Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes.

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.

Cardiac K(ATP) channel alterations associated with acclimation to hypoxia in goldfish (Carassius auratus L.).

Goldfish (Carassius auratus L.) are highly tolerant of environmental hypoxia, and with appropriate acclimation may survive and remain active for several days in the complete absence of oxygen. Previous work suggests that the hypoxia-induced activation of cardiac ATP-sensitive potassium (KATP) channels serves to increase tolerance of low oxygen in many species. For goldfish, we have previously characterized a nitric oxide (NO)- and cGMP-dependent pathway by which this channel activation occurs in acute hypoxia. The purpose of the present study was to resolve alterations in KATP channel activity and relevant gene expression in response to acclimation under moderately hypoxic conditions (2.6mg O2/L for seven days at 22°C). Intracellular action potential duration in excised ventricles from hypoxia-acclimated animals was significantly (p<0.05) reduced at both 50% and 90% of full repolarization relative to those from normoxia-acclimated fish. In cell-attached ventricular membrane patches from hypoxia-acclimated goldfish, sarcolemmal KATP channel open probability (NPo) was significantly enhanced vs. control. Of the two genes coding for the pore-forming subunits of cardiac KATP channels (Kir6.1 and Kir6.2), mRNA transcription of kcnj8 (revealed by quantitative real-time PCR) was unchanged while kcnj11 was downregulated in response to chronic low oxygen. The mRNA levels for hif1a (hypoxia inducible factor 1α) in the hearts of hypoxia-acclimated fish were significantly enhanced, as was nitric oxide synthase (nos2) and the sulfonylurea receptor regulatory subunit (sur2, abcc9). These data suggest that prior whole-animal acclimation to chronic hypoxia enhances cardioprotective sarcolemmal KATP currents by altering transcription of regulatory proteins.