An Electronic-Based Curriculum to Train Acute Care Providers in Rural Haiti and India.

Background: Access to a trained, competent health care workforce remains a challenge globally, particularly in rural settings. To bridge this gap, the World Health Organization calls for innovations in electronic learning and task shifting. Yet, these approaches are underutilized due to cost, challenges associated with implementing technology, and a lack of suitably educated trainees.

Antihypertensive actions of moderate hyperbilirubinemia: role of superoxide inhibition.

Background: Moderate (approximately 2-fold) increases in plasma unconjugated bilirubin levels are able to attenuate the development of angiotensin II (Ang II)-dependent hypertension. To determine the specific role of decreases in superoxide production to the blood pressure-lowering effects of moderate hyperbilirubinemia (MHyB), we performed this study, in which the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin was given to Ang II-infused mice in the presence and absence of moderate hyperbilirubinemia.

Methods: Apocynin (14mM) was administered in the drinking water prior to treatment with UDP-glucuronosyltransferase 1A1 antisense morpholino (16 μg/kg), which was administered by intravenous injection every third day.

Expression of heme oxygenase-1 in thick ascending loop of henle attenuates angiotensin II-dependent hypertension.

Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments.

Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension.

The goal of this study was to test the hypothesis that renal medullary heme oxygenase (HO) acts as a buffer against Ang-II dependent hypertension. To test this hypothesis, renal medullary HO activity was blocked using QC-13, an imidazole-dioxolane HO-1 inhibitor, or SnMP, a classical porphyrin based HO inhibitor. HO inhibitors were infused via IRMI catheters throughout the study starting 3 days prior to implantation of an osmotic minipump which delivered Ang II or saline vehicle.

Induction of heme oxygenase-1 attenuates sFlt-1-induced hypertension in pregnant rats.

Preeclampsia (PE) is one of the leading causes of fetal and maternal morbidity, affecting 5-10% of all pregnancies, and lacks an effective treatment. The exact etiology of the disorder is unclear, but placental ischemia has been shown to be a central causative agent. In response to placental ischemia, the antiangiogenic protein fms-like tyrosine kinase-1 (sFlt-1), a VEGF antagonist, and reactive oxygen species are secreted, leading to the maternal syndrome.

Blood pressure and renal blow flow responses in heme oxygenase-2 knockout mice.

Heme oxygenase (HO) is the enzyme responsible for the breakdown of heme-generating carbon monoxide (CO) and biliverdin in this process. HO-2 is the constitutively expressed isoform in most tissues, such as the kidney and vasculature. CO generated by HO is believed to be an important vasodilator in the renal circulation along with another gas, nitric oxide (NO).

Inhibition of biliverdin reductase increases ANG II-dependent superoxide levels in cultured renal tubular epithelial cells.

Induction of heme oxygenase-1 (HO-1) in the renal medulla increases carbon monoxide and bilirubin production and decreases ANG II-mediated superoxide production. The goal of this study was to determine the importance of increases in bilirubin to the antioxidant effects of HO-1 induction in cultured mouse thick ascending loop of Henle (TALH) and inner medullary collecting duct (IMCD3) cells. Bilirubin levels were decreased by using small interfering RNAs (siRNAs) targeted to biliverdin reductase (BVR), which is the cellular enzyme responsible for the conversion of biliverdin to bilirubin.