All posts by thorn

Plato BioPharma, Inc. Scientists Coauthor Science Translational Medicine paper

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Plato BioPharma Inc. (PBI) Founder and CEO, Dr. Craig F. Plato, announced the co-authorship of a research paper appearing in the 12 March, 2014 issue of Science Translational Medicine.  The paper, titled “Intestinal Inhibition of the Na+/H+Exchanger 3 Prevents Cardiorenal Damage in Rats and Inhibits Na+ Uptake in Humans” describes the effects of tenapanor, a compound that reduces the absorption of dietary sodium in the GI tract.  Ardelyx, a Fremont-based biotechnology company, and their pharmaceutical…

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Age exacerbates chronic catecholamine-induced impairments in contractile reserve in the rat

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Contractile reserve decreases with advancing age and chronic isoproterenol (ISO) administration is a well-characterized model of cardiac hypertrophy known to impair cardiovascular function. This study evaluated whether nonsenescent, mature adult rats are more susceptible to detrimental effects of chronic ISO administration than younger adult rats. Rats received daily injections of ISO (0.1 mg/kg sc) or vehicle for 3 wk. ISO induced a greater impairment in contractile reserve [maximum of left ventricular pressure development (Δ+dP/dt(max))] in…

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A high-performance liquid chromatography assay for quantification of cardiac myosin heavy chain isoform protein expression

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Stress signaling in the myocardium results in enhanced expression of embryonic β-myosin heavy chain (β-MyHC) and reduced expression of adult α-myosin heavy chain (α-MyHC), with the net outcome of diminished myofibrillar ATPase activity and impaired contractility. Pharmacological approaches aimed at preventing this myosin isoform “switch” could provide therapeutic benefit to patients with heart failure. Myosin isoform protein expression is typically quantified using gel electrophoresis methods, which are time-consuming and prone to variability. Here we describe…

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Bioimpedance spectroscopy for the estimation of body fluid volumes in mice

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Conventional indicator dilution techniques for measuring body fluid volume are laborious, expensive, and highly invasive. Bioimpedance spectroscopy (BIS) may be a useful alternative due to being rapid, minimally invasive, and allowing repeated measurements. BIS has not been reported in mice; hence we examined how well BIS estimates body fluid volume in mice. Using C57/Bl6 mice, the BIS system demonstrated <5% intermouse variation in total body water (TBW) and extracellular (ECFV) and intracellular fluid volume (ICFV)…

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Acute effects of endothelin receptor antagonists on hepatic hemodynamics of cirrhotic and noncirrhotic rats

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Hepatic and circulating endothelin-1 (ET-1) are increased in patients with cirrhosis and in cirrhotic animals. However, the distinct roles of ET receptor subtypes ETA and ETB in cirrhosis and portal hypertension (PHT) have not been clearly elucidated. Thus, we studied the effects of selective ET-1 antagonists (ETA-ant or ETB-ant) and nonselective ET-1 antagonist (ETA/B-ant) on hepatic hemodynamics in cirrhotic rats. Liver fibrosis and PHT were induced by complete bile duct ligation (BDL) in rats. Two…

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MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury

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Vascular injury triggers dedifferentiation and cytoskeletal remodeling of smooth muscle cells (SMCs), culminating in vessel occlusion. Serum response factor (SRF) and its coactivator, myocardin, play a central role in the control of smooth muscle phenotypes by regulating the expression of cytoskeletal genes. We show that SRF and myocardin regulate a cardiovascular-specific microRNA (miRNA) cluster encoding miR-143 and miR-145. To assess the functions of these miRNAs in vivo, we systematically deleted them singly and in combination...
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