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S A Mousa

Publications and source records attributed to S A Mousa.

116 records · Page 7Linked to original sources
PubMed1989

Myocardial cytoprotective efficacy of azapropazone in a canine heart model of regional ischemia and reperfusion.

The present study assessed the efficacy of azapropazone (AZA) in pentobarbital-anesthetized dogs subjected to 120 min of regional ischemia [left anterior descending coronary artery (LAD) ligation] followed by 5 h of reperfusion. Azapropazone was given 30 min prior to LAD occlusion (100 mg/kg i.v.), 35 min prior to LAD release (50 mg/kg, i.v.), and at 2.5 h postreperfusion (50 mg/kg i.v.). Regional myocardial blood flow (RMBF) and area at risk (AAR) were determined with radiolabeled microspheres. The degree and extent of ischemia (anaerobic metabolism) and necrosis were delineated with 14C-deoxy-2-D-glucose (14C-DG) and 111In-antimyosin, respectively, in control (n = 7) and AZA (n = 7)-treated groups. In mild (60-80% normal RMBF) and moderate (30-60% normal RMBF) flow-restricted areas, AZA resulted in a significant decrease in the degree and extent of ischemia (p less than 0.01) with the limitation of infarct size (p less than 0.01). However, AZA did not produce a significant infarct size limitation in the severe flow-restricted area (0-30% of normal RMBF). The effect of AZA is expressed primarily in moderate flow-restricted myocardium with the subsequent infarct size limitation.

Anaerobiosis↗
PubMed1989

99mTc hexakis-t-butyl isonitrile (TBI): an agent for the diagnosis of coronary artery diseases.

Basic and clinical studies were undertaken to determine pharmacokinetic mechanisms, blood flow-related characteristics and potential clinical utility of the 99mTc hexakis-t-butyl isonitrile (TBI) in the non-invasive diagnosis of ischemic heart diseases. Pharmacokinetic studies with TBI in animals demonstrated a high initial lung, heart and liver uptake. The lung clears at a relatively faster rate, the activity in the heart remained constant with a buildup of activity in the liver. These pharmacokinetic characteristics allowed for a myocardial imaging at 30-45 min post-injection at rest. The regional myocardial distribution of TBI was shown to be linearly related to microsphere-determined regional myocardial blood flow with a redistribution potential in transient ischemic myocardium (i.e., mimics 201Tl). The first pass extraction fraction (in vitro) for TBI was shown to be nearly 100% and independent on flow levels. In general, the slow tissue clearance rate or the lack of it might be due to the high degree of lipophilicity with the complete lack of any hepatic or extrahepatic metabolism to a less lipophilic metabolite. The complex demonstrated a high degree of cardiac membrane association. The net extraction in isolated heart slices was shown to be dependent on pH and temperature, independent of energy. The clinical studies demonstrated a similar pharmacokinetic pattern to the animal studies and documented the perfusion and ventricular function utility of TBI in the diagnosis of ischemic heart diseases.

Adult↗
PubMed1988

Tolerance to tobacco smoke- and nicotine-induced analgesia in rats.

Acute exposure of male Sprague-Dawley rats to either nicotine or tobacco smoke results in analgesia as measured by tail-flick latencies. A second treatment, 24 hr after the first, failed to produce analgesia, thereby demonstrating the rapid development of tolerance. The restraint which was a necessary part of the tobacco smoke exposure also produced analgesia, although of a more transient nature and lesser magnitude than that resulting from tobacco smoke exposure. Tolerance also developed to restraint stress-induced analgesia. The long-term (43 weeks) daily exposure of rats to tobacco smoke or restraint stress resulted in the development of cross-tolerance, suggesting that these two procedures share, at least in part, a common mechanism. Additionally, long-term tobacco smoke exposure resulted in an increased tail-flick latency when the animals had been withdrawn from tobacco smoke for 24 hr, suggesting the development of tolerance. The data also suggest a differential time course for the development of tolerance and dependence. This is the first report that addresses the effect of acute and chronic tobacco smoke exposure on pain sensitivity.

Analgesia↗
PubMed1987

Characterization of in vivo chemistry of cations in the heart.

A variety of laboratory procedures can be used to define the chemistry and pharmacokinetics of myocardial cationic imaging agents. These methods are utilized to define the in vivo chemistry of cationic heart agents, in order to understand the kinetics and mechanisms of: tissue and cellular transport, subcellular distribution, and intracellular localization. Transport across cell membranes can be active, passive or facilitated. Studies performed in erythrocytes, heart cells, slices and isolated perfused hearts using methods for separation of metabolites have shown a high degree of myocardial specificity for [99mTc]hexakis alkyl isonitrile by an uptake mechanism different from 201Tl. These studies demonstrate the importance of in vivo chemistry and pharmacokinetics in the development of new radiopharmaceuticals.

Animals↗
PubMed1986

Stabilization of methionine-enkephalin in human and rat blood.

Methods of preventing the degradation of 3H-methionine-enkephalin (3H-ME) in human blood both at 37 degrees C and under conditions of immediate cooling were examined. We found that, contrary to previous suggestions, use of aprotinin (with or without immediate cooling) was ineffective in preventing the degradation of 3H-ME in blood. Thus, previous reports on the circulating levels of ME which relied on such procedures to stabilize the ME may have reported artifactually low values. However, we found that citric acid effectively prevents 3H-ME breakdown in both human and rat blood. Thus, we propose the use of citric acid, mixed with blood immediately upon collection, as an effective method for the stabilization of ME in blood.

Animals↗
PubMed1985

Measurement of proenkephalin A-derived peptides in biological tissues by high pressure liquid chromatography coupled with amperometric electrochemical detection.

We describe an analytic method for the separation and quantitation of a number of proenkephalin A-derived peptides using high pressure liquid chromatography coupled with amperometric electrochemical detection (HPLC-AECD). Initially, we coupled our HPLC separation system with AECD in series with a UV detector for additional confirmation of peak specificity. AECD provided a 10(6)-fold increase in sensitivity over UV detection for these peptides. In addition to Met-enkephalin (ME), ME-Arg, ME-Arg-Phe, ME-Arg-Gly-Leu, Leu-enkephalin (LE) and LE-Arg (Dyn 1-6), we separated and detected the sulfoxides of ME and its extended peptides. Subsequently, we used minor modifications of the isocratic mobile phase to separate and detect enkephalin-related peptides with greater sensitivity and shorter chromatographic run times; each of these mobile phases was used to separate and detect two to three peptides. We have applied this HPLC-AECD methodology to quantitate ME, ME-Arg-Phe, ME-Arg-Gly-Leu and LE in pheochromocytoma tumors.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Novel small molecule alpha v integrin antagonists: comparative anti-cancer efficacy with known angiogenesis inhibitors.

Recent evidence supports the involvement of integrins in angiogenesis: blockade of alpha v beta 3 and alpha v beta 5 integrins disrupts angiogenesis leading to decreased blood vessel formation and hence decreased tumor growth. We hypothesized that av antagonists could inhibit tumor growth in tumor cells devoid of alpha v beta 3 integrins. We evaluated SM256 and SD983, novel small molecules that are specific av antagonists in mouse models of angiogenesis and tumorigenesis, and compared them with standards: TNP470, a fumagillin analog in the clinic, and flavopiridol, a cell cycle kinase inhibitor. In vitro SM256 was a selective alpha v beta 3 inhibitor with an IC50 = 4nM, and the affinity of SD983 against the mouse endothelial alpha v beta 3 integrin yielded an IC50 = 2nM and an IC50 = 54nM against alpha v beta 5. In the mouse Matrigel model of angiogenesis SM256 decreased blood vessel formation (hemoglobin content) with an ED50 = 0.055 ug/kg/day, tenfold more potent than TNP470. SG545, an ester of SD983, decreased blood vessel formation with an ED50 = 6 ug/kg/day, while flavopiridol ED50 = 18 ug/kg/day. In the mouse xenograft model, using human colon carcinoma RKO cells that do not express alpha v beta 3 but express alpha v beta 5, tumor growth was inhibited by SG545 (10 mg/kg/day) and flavopiridol (5 mg/kg/every other day) 40% and 70%, respectively (p < 0.05). Although the proliferative index (measured by BrdU incorporation) was not significantly changed with SM256, SG545 or flavopiridol (29-32%), the apoptotic index increased significantly (p < 0.05) in the SM256 and SG545-treated groups (2.3-2.7%) compared with controls (1.1%), suggesting increased cell death contributed to decreased tumor volumes. Neovascularization decreased with SM256 and SG545 treatment. The data demonstrate that potent selective av antagonist can target endothelial cells, tumor cells, inhibit angiogenesis and inhibit tumor growth.

Animals↗