University of Texas System

About: University of Texas System is a education organization based out in Austin, Texas, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 13901 authors who have published 10925 publications receiving 319328 citations. The organization is also known as: UT System.

Inhibition of Interleukin-1-α-Induced Nitric Oxide Synthase in Vascular Smooth Muscle and Full Reversal of Interleukin-1-α-Induced Hypotension by Nω-Amino-L-arginine

Abstract: BACKGROUND Interleukin-1-alpha (IL-1) is a cytokine with potentially therapeutic immunoproliferative and tumoricidal activities. Preliminary clinical studies suggest that use of IL-1 may be restricted by dose-limiting hypotension. PURPOSE The purpose of this study was to investigate the role of nitric oxide (NO.) as a possible mediator of this hypotension. METHODS Cytokine-treated rat aortic smooth muscle cells were assayed for nitrite production, a stable breakdown product of nitric oxide. Nitric oxide synthase from smooth muscle cells was partially characterized in cytosol preparations using a novel Fe(2+)-myoglobin method to test for nitric oxide production. To determine the role of NO. on the immunorestorative and antineoplastic activity of IL-1, N omega-amino-L-arginine (NAA) or N omega-monomethyl-L-arginine (NMA), inhibitors of nitric oxide synthase, were added to either cultures of IL-1-dependent T cells or A375 melanoma cells exposed to IL-1. To investigate the effects of NAA in vivo, pentobarbital anesthetized dogs, which were made hypotensive by administration of IL-1, received a single intravenous bolus dose of NAA. The effects of NAA were then reversed by the administration of L-arginine. RESULTS Our results show that cultured IL-1-activated rat aortic smooth muscle cells synthesize nitric oxide, a potent vasodilator. Induction of nitric oxide synthase is augmented by interferon-gamma and blocked by IL-1 receptor antagonist and by inhibitors of RNA or protein synthesis. Nitric oxide synthesis by IL-1-activated smooth muscle cells is inhibited by NAA, NMA, and N omega-nitro-L-arginine (NNA) with ED50 (i.e., effective dose for 50% inhibition) values of 20, 60, and 1000 microM, respectively; this rank order of inhibition is characteristic of an agonist-unregulated, inducible isoform of nitric oxide synthase. In smooth muscle cells, inhibition of NO. synthesis by NAA is reversed by excess L-arginine. Consistent with the induction of unregulated NO. synthesis in vascular smooth muscle in vivo, administration of IL-1 (50 micrograms/kg) to dogs caused a 33.5% decrease in systemic vascular resistance and a 28% decrease in blood pressure within 3 hours. Subsequent administration of NAA (20 mg/kg) rapidly and completely reversed the hypotension and increased systemic vascular resistance; these effects of NAA were reversed by L-arginine. Neither the immunoproliferative nor the tumoricidal activity of IL-1 was diminished by NAA. CONCLUSIONS Our results indicate that (a) vascular smooth muscle is a likely source as well as a target of IL-1-induced NO. synthesis, causing vasodilatation and hypotension, (b) nitric oxide synthase inhibitors can fully reverse this hypotension, and (c) the therapeutically useful properties of IL-1 are not diminished by nitric oxide synthase inhibitors. IMPLICATIONS Administration of inhibitors of nitric oxide synthase can reverse the pathological cardiovascular effects of IL-1 at concentrations that do not interfere with the potentially useful immunoproliferative or tumoricidal effects of this cytokine. In the context of the current clinical trials of IL-1, this finding would represent a very significant advantage.

Catheter for intravascular ultrasound and photoacoustic imaging

Abstract: A design and a fabrication method for an intravascular imaging and therapeutic catheters for combined ultrasound, photoacoustic, and elasticity imaging and for optical and/or acoustic therapy of hollow organs and diseased blood vessels and tissues are disclosed in the present invention. The invention comprises both a device—optical fiber-based intravascular catheter designs for combined IVUS/IVPA, and elasticity imaging and for acoustic and/or optical therapy—and a method of combined ultrasound, photoacoustic, and elasticity imaging and optical and/or acoustic therapy. The designs of the catheters are based on single-element catheter-based ultrasound transducers or on ultrasound array-based units coupled with optical fiber, fiber bundles or a combination thereof with specially designed light delivery systems. One approach uses the side fire fiber, similar to the one utilized for biomedical optical spectroscopy. The second catheter design uses the micro-optics in the manner of a probe for optical coherent tomography.

Dexamethasone in the Treatment of Experimental Haemophilus influenzae Type b Meningitis

Abstract: A model of experimental lapin meningitis was used to assess the effect of meningeal inflammation caused by Haemophilus influenzae type b on development of brain edema, increase in intracranial pressure, and production of brain lactate. Four treatments were assessed: dexamethasone alone, dexamethasone plus ceftriaxone, ceftriaxone alone, and no treatment. The brain water content in untreated rabbits with meningitis was 419 +/- 10 g of H2O/100g of dry weight after 29 hr of infection (vs. 405 +/- 14 in uninfected rabbits; P less than .05). In rabbits treated with dexamethasone, dexamethasone plus ceftriaxone, or ceftriaxone alone, these values were 404 +/- 12, 406 +/- 12, and 411 +/- 14 g, respectively (P greater than .05). The cerebrospinal fluid (CSF) pressure and lactate levels were significantly increased in all animals during the 24 hr of meningeal inflammation (P less than .005), and these levels were comparably reduced after 9 hr of treatment. Although the values for brain water content, CSF pressure, and lactate concentrations in infected animals treated with ceftriaxone plus dexamethasone were not significantly different from those in animals treated with ceftriaxone alone, the values were consistently lower in the former group.