NAD(P)H oxidase, superoxide dismutase, catalase, glutathione peroxidase and nitric oxide synthase expression in subacute spinal cord injury

Primary trauma to the spinal cord triggers a cascade of cellular and molecular events that promote continued tissue damage and expansion of the lesion for extended periods following the initial injury. Oxidative and nitrosative stresses play an important role in progression of spinal cord injury (SCI). In an attempt to explore the biochemical origin of oxidative/nitrosative stress associated with secondary SCI, we studied expression of the superoxide (O2*-)-generating enzyme, NAD(P)H oxidase, antioxidant enzymes [superoxide dismutase (CuZn SOD, Mn SOD), catalase, glutathione peroxidase (GPX)], nitric oxide synthases (NOS) and a byproduct of NO-O2*- interaction (nitrotyrosine) in the spinal cord tissues of rats 16 h and 14 days after surgical resections of a 5-mm segment of the cord below T8 or sham-operation. Immunodetectable NAD(P)H oxidase subunits (gp91phox and P67phox), Mn SOD, inducible NOS (iNOS), endothelial NOS (eNOS), and nitrotyrosine were elevated in the transected cords on day 1 and day 14. Neuronal NOS (nNOS) was unchanged on day 1 and significantly depressed on day 14. GPX was unchanged on day 1 and significantly elevated on day 14. Catalase was unchanged in the cord tissue surrounding the transection site at both points. Thus, concurrent upregulations of NAD(P)H oxidase, eNOS and iNOS (but not nNOS), work in concert to maintain oxidative and nitrosative stress in the injured cord tissue.     

Microvascular and tubulointerstitial injury associated with chronic hypoxia-induced hypertension

BACKGROUND: Rats submitted to chronic hypoxia develop hypertension that persists despite cessation of the hypoxia or correction of the hematocrit. We examined whether chronic hypoxia might induce subtle renal injury since studies in other animal models of hypertension suggest this may cause persistent hypertension. METHODS: Chronic hypoxia was induced in rats by placement in a hypobaric chamber for up to 24 days. Blood pressure and kidney biopsies were performed at baseline, 6 hours, 24 hours, and 24 days of hypoxia. RESULTS: Chronic hypoxia induced hypertension and erythrocytosis at 24 days. Acute hypoxia was associated with endothelial cell swelling in arterioles (6 and 24 hours), followed by thickening of the arterioles at 24 days. Subtle tubulointerstitial injury and inflammation occurred and was progressive. The influx of macrophages increased steadily over the 24 days and was associated with a progressive increase in interstitial collagen III deposition. Hypoxia was associated with increased tubular expression of osteopontin as early as 6 hours, the same period when an increase of proximal tubular cell proliferation occurred. Interstitial cell proliferation peaked twice, at 6 hours and at 24 days. Glomerular hypertrophy was manifest at 24 days. CONCLUSION: Both afferent arteriolar disease and subtle tubulointerstitial inflammation and injury occur early in hypoxic rats. These changes may predispose these animals to persistent hypertension.     

HMG-CoA reductase,cholesterol 7alpha-hydroxylase,LCAT, ACAT,LDL receptor,and SRB-1 in hereditary analbuminemia

BACKGROUND: Hereditary analbuminemia is associated with hypercholesterolemia, which has been shown to be primarily caused by increased extrahepatic production of cholesterol. Nagase rats with hereditary analbuminemia (NAR) have been used as a model to dissect the effect of primary hypoalbuminemia from that caused by proteinuria in nephrotic syndrome. The present study was undertaken to explore the effect of hereditary analbuminemia on protein expression of the key factors involved in cholesterol metabolism. METHODS: Hepatic tissue protein abundance of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7alpha-hydroxylase (a rate-limiting enzyme in cholesterol catabolism), low density lipoprotein (LDL) receptor, high density lipoprotein (HDL) receptor (SRB-1), acyl-coA cholesterol acyltransferase-2 (ACAT-2), and plasma concentration of lecithin cholesterol acyltransferase (LCAT), as well as HMG-CoA reductase, ACAT, and LCAT activities were determined in fasting male NAR and Sprague-Dawley control rats. RESULTS: The NAR group exhibited significant up-regulation of HMG-CoA reductase protein abundance but normal HMG-CoA reductase enzymatic activity. This was coupled with a significant up-regulation of cholesterol 7alpha-hydroxylase and a mild up-regulation of ACAT protein abundance and activity. However, hepatic LDL receptor and HDL receptor and plasma LCAT protein concentration and activity were normal in NAR. CONCLUSION: Hypercholesterolemia in NAR is associated with elevated hepatic HMG-CoA reductase protein abundance, but normal HMG-CoA reductase activity. These findings point to post-translational regulation of this enzyme and favor an extrahepatic origin of hypercholesterolemia in NAR. The observed up-regulation of cholesterol 7alpha-hydroxylase represents a compensatory response to the associated hypercholesterolemia. Unlike nephrotic syndrome, which causes severe LDL receptor, HDL receptor, and LCAT deficiencies, hereditary analbuminemia does not affect these proteins.     

Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.     

Follicular vascularity--the predictive value of transvaginal power Doppler ultrasonography in an in-vitro fertilization programme: a preliminary study

The aim of this prospective study was to investigate the ability of transvaginal power Doppler ultrasonography to assess the relationship between follicular vascularity and outcome in women undergoing in-vitro fertilization. Each of 38 subjects underwent a single transvaginal power Doppler ultrasound scan on the day of oocyte collection, where the vascularity of individual ovarian follicles was assessed, using a subjective system, and graded 1 to 4. In addition, conventional pulsatility indices (PI) of the uterine and intra-ovarian (stromal) arteries were calculated, which showed no significant differences between the pregnant and non-pregnant groups. Using power Doppler ultrasonography, a total of 188 follicles was studied. The follicular vascularity grade was found to be independent of follicular size and there was no significant difference in fertilization rates with different degrees of vascularity, although there was a trend towards higher fertilization rates with higher grade vascularity. There were 10 pregnancies, giving a pregnancy rate of 26.3% per embryo transfer. Pregnancies were confined to those women whose embryos were derived from follicles with grade 3 and 4 vascularity (pregnancy rates per embryo transfer of 12.5 and 61.5% respectively), with only those from grade 4 follicles resulting in livebirths. This preliminary study suggested that high grade follicular vascularity is associated with increased pregnancy rate and that there is a possible link between follicular vascularity and implantation potential.      

Treatment of glomus tumours.: A retrospective survey

A retrospective survey of symptomatology, treatment and course of disease in 45 patients with glomus tumours treated between 1959 and 1986 at the Radium Centre and ENT Department of the Aarhus University Hospital is presented. Nine patients were treated surgically, 7 had surgery and irradiation combined, and 25 patients were treated solely with radiation therapy. Six patients developed recurrence of tumours. Two patients died of tumour, one of them with pulmonary metastases.     

Noninvasive evaluation of knee meniscal tears: preliminary comparison of MR imaging and CT

One hundred twenty knees were examined prospectively with both axial computed tomography (CT) and magnetic resonance (MR) imaging to compare the value of these techniques in patients with clinical evidence of meniscal tears. Sixty-four of these knees were subsequently evaluated with diagnostic arthroscopy. In this group, CT was superior to MR imaging for meniscus evaluation in 29.7% of the knees, equal to MR in 54.7%, and inferior to MR in 15.6%. Although surface-coil MR imaging shows great promise and has numerous advantages over more conventional techniques, this preliminary experience suggests that, at least with certain imaging equipment and techniques, CT may be slightly more efficacious than 0.5-T MR imaging in meniscus evaluation. However, further comparative studies at higher field strengths are needed before the relative roles of CT and MR imaging can be established.     

Feasibility of an Emergency Department–Based, Risk-Targeted Voluntary HIV Screening Program

Study objective: To assess the feasibility and effectiveness of an emergency department–based, risk-targeted voluntary HIV screening program. Methods: We prospectively enrolled consenting adult IV drug users (IDUs) not known to have HIV infection in the ED of a large inner-city hospital with a high rate of HIV infection among patients during a 10-week trial. Study patients were given confidential HIV pretest and risk-reduction counseling, with 10- to 14-day on-site ED follow-up. Follow-up included posttest counseling, reinforcement of risk-reduction practices, and a $10 incentive to cover transportation costs. HIV seropositive patients were referred to the hospital HIV clinic for further evaluation and treatment. Results: Of 200 eligible IDUs, 168 (84%) consented to HIV testing. Of the 104 (62%) who returned for follow-up, 17 (16%) tested positive for HIV. Of these patients, 6 (35%) kept their initial hospital HIV clinic referral appointment, a rate consistent with the experience of the hospital HIV clinic. Of nine patients in whom CD4+ counts were performed at time of the visit, three (33%) had counts less than 200. At 3-month follow-up, 4 of 20 active IDUs (20%) had reportedly ceased drug use because of the program. The complete program cost was an estimated $16,659, $99 per enrolled patient and $521 per HIV-positive patient. Conclusion: An ED-based, risk-targeted HIV screening program is feasible and over time could detect a significant number of asymptomatic HIV-infected individuals, including those who should receive antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia therapy (CD4+ count less than 200). An additional benefit of ED-based HIV screening in high-prevalence EDs is the opportunity to conduct successful risk-reduction counseling in some high-risk individuals. [Kelen GD, Hexter DA, Hansen KN, Humes R, Vigilance PND, Baskerville M, Quinn TC: Feasibility of an emergency department–based, risk-targeted voluntary HIV screening program. Ann Emerg Med June 1996;27:687-692.]     

Adverse effects of (15S)-15-methyl-prostaglandin E1 in normal and paraquat-exposed rats

Single, daily injections of approximately 1 mg/kg of (15S)-15-methyl-PGE1 (mPGE1), a PGE1 analog, have been reported to inhibit inflammation and to prolong survival in several animal models of local and systemic inflammation. We examined the effect of this dose of mPGE1 on paraquat toxicity in rats. A significant increase in early mortality was identified in mPGE1-treated rats as early as 3 hr following injection of paraquat and appeared associated with increased respiratory effort. Rats given mPGE1 without paraquat also appeared to increase respiratory effort but did not die. Rats killed at 3 hr following injections demonstrated increased lung weights in both paraquat-injected and control animals receiving mPGE1. Although a neutrophilia was identified in these animals, no significant increase in lung lavage neutrophils or albumin was identified. These data suggest that large intermittent doses of a PGE1 analog may adversely affect the respiratory system of normal and injured animals, and will accelerate mortality following exposure to potentially lethal doses of paraquat.