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The present study tested the hypothesis that murine (m)IFN-[beta] or mIFN-[[alpha].sub.2] can eliminate cardiac viral load and protect cardiomyocytes from injury in animals infected with coxsackievirus B3 (CVB3). CVB3-inoculated male Balb/c mice exhibited signs of illness, including lethargy, progressive weight loss, and death (10% on day 3 and 100% on day 8). Cardiac viral load was high [4,277 [+ or -] 1,009 plaque-forming units and 25 [+ or -] 5 copies CVB3/hypoxanthine guanine phosphoribosyl transferase 1 mRNA] on day 4. The cardiac tissue exhibited severe inflammatory infiltration and myocyte damage with an average myocarditis integrated pathology score of 2.1 [+ or -] 0.2 on day 7. Most of the mice infected with CVB3 also developed epicarditis, and 55% had intraventricular thrombi present. Treatment with mIFN-[beta] [2.5 to 10 million international units (MIU)/kg] dose-dependently improved the general health status in CVB3-inoculated mice, as evidenced by reduction in weight loss, prevention of death, elimination of cardiac viral load, protection of myocytes from injury, decrease in inflammatory cell infiltration, and attenuation of intraventricular thrombus formation. Treatment with 10 MIU/kg mIFN-[[alpha].sub.2] resulted in a similar level of efficacy as that induced by 5 MIU/kg mIFN-[beta], with the exception that mIFN-[[alpha].sub.2] did not reduce cardiac CVB3 mRNA. However, mIFN-[[beta].sub.2] , but not any dose group of mIFN-[beta], significantly attenuated CVB3-induced epicarditis. These data demonstrate antiviral effects for both mIFN-[beta] and mIFN-[[alpha].sub.2], which lead to protection of the mice from CVB3-induced myocarditis. However, the potential mechanisms leading to a differential host response for the two isoforms of mIFN remain to be elucidated. viral cardiomyopathy; myocyte infection; antiviral action; immunomodulation doi:10.1152/ajpheart.00154.2007

A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve settings, from several microelectrodes in parallel.

Hartley, Craig J., Anilkumar K. Reddy, Sridhar Madala, Baby Martin-McNulty, Ronald Vergona, Mark E. Sullivan, Meredith Halks-Miller, George E. Taffet, Lloyd H. Michael, Mark L. Entman, and YiXin Wang. Hemodynamic changes in apolipoprotein E-knockout mice. Am J Physiol Heart Circ Physiol 279: H2326-H2334, 2000.--Apolipoprotein E-knockout (ApoE-KO) mice develop advanced atherosclerotic lesions by 1 yr of age and have been well characterized pathologically and morphologically, but little is known regarding their cardiovascular physiology and hemodynamics. We used noninvasive Doppler ultrasound to measure aortic and mitral blood velocity and aortic pulse-wave velocity in 13-mo-old ApoE-KO and wild-type (WT) mice anesthetized with isoflurane. In other mice from the same colony, we measured systolic blood pressure, body weight, heart weight, cholesterol, and hematocrit. Heart rate and blood pressure were comparable (P = not significant) between ApoE-KO and WT mice, but significant decreases (P [is less than] 0.001) were found in body weight (-22%) and hematocrit (-11%), and significant increases were found in heart weight (+23%), aortic velocity (+60%), mitral velocity (+81%) (all P [is less than] 0.001), and pulse-wave velocity (+ 13%, P [is less than] 0.05). We also found inflections in the aortic arch velocity signal consistent with enhanced peripheral wave reflection. Thus ApoE-KO mice have phenotypic alterations in indexes of peripheral vascular resistance and compliance ,and significantly elevated cardiac outflow velocities and heart weight-to-body weight ratios. atherosclerosis; cardiac output; hypertrophy; ultrasonics

Wang, Yi-Xin, Meredith Halks-Miller, Ron Vergona, Mark E. Sullivan, Richard Fitch, Cornell Mallari, Baby Martin-McNulty, Valdeci Da Cunha, Ana Freay, Gabor M. Rubanyi, and Katalin Kauser. Increased aortic stiffness assessed by pulse wave velocity in apolipoprotein E-deficient mice. Am. J. Physiol. Heart Circ. Physiol. 278: H428-H434, 2000.--Atherosclerosis develops and progresses spontaneously in apolipoprotein E-knockout (apoE-KO) mice. A direct consequence of atherosclerosis is an increase in vascular stiffness. Pulse wave velocity (PWV) has been used to assess the stiffness of large vessels and was found to be increased in patients with atherosclerosis. In the present study, aortic stiffness was assessed by PWV in 4- and 13-mo-old apoE-KO mice and age-matched controls (C57BL/6J). In 13-mo-old apoE-KO mice with extensive atherosclerotic lesions in the aorta (61 [+ or -] 4%), PWV increased significantly (3.8 [+ or -] 0.2 m/s) compared with controls (2.9 [+ or -] 0.2 m/s). Endothelial nitric oxide (EDNO)-mediated vasorelaxation in response to ACh was markedly diminished in the aortic rings isolated from 13-mo-old apoE-KO mice compared with age-matched controls. In contrast, in 4-mo-old apoE-KO mice with only moderate atherosclerotic lesions in the aorta (23 [+ or -] 5%), there were no significant changes in PWV and EDNO-mediated relaxation compared with controls. Blood pressure was not different among the four groups of mice. There were no significant differences in endothelium-independent vascular responses to sodium nitroprusside among different groups investigated. Histological evaluation revealed focal fragmentation of the elastic laminae in the aortic walls of 13-mo-old apoE-KO mice. These results demonstrate for the first time that aortic stiffness determined by PWV increases in 13-mo-old apoE-KO mice. Endothelial dysfunction and elastic destruction in vascular wall caused by atherosclerosis may have contributed compliance; elastin degradation; endothelium-dependent relaxation; nitric oxide

Objective: The aim of this study was to evaluate clinical use of NIPT at gestational ages of 23 weeks and above.Methods: A cohort of 5579 clinical patients with singleton gestations of 23 weeks or greater submitting a blood sample for NIPT in an 18-month period were selected for this study. Clinical outcomes were requested for samples with NIPT results indicating fetal aneuploidy and compared with NIPT findings to confirm concordance or discordance.Results: A review of clinical indications revealed that a significantly (p < 0.0001) larger proportion of late-gestation samples indicated abnormal ultrasound findings with or without other indications, 6.2% and 42.1%, compared with early-gestation samples, 1.8% and 6.0%, respectively. Of 5372 reported late-gestation samples, 151 (2.8%) were reported as aneuploidy detected or suspected. In late-gestation samples, the overall observed positive predictive value (PPV) for NIPT was 64.7%, with an observed PPV of 100% in the subset of cases with multiple clinical indications including abnormal ultrasound findings.Conclusions: NIPT is a highly accurate prenatal screening option for women after 23 weeks of gestation. Women who presented for NIPT in the latter stages of pregnancy more frequently specified clinical indications of abnormal ultrasound findings than women who entered screening earlier in pregnancy. [ABSTRACT FROM AUTHOR]