Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-06-07
1998-01-20
Cook, Rebecca
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 31415
Patent
active
057101728
ABSTRACT:
Histidine has been found to be efficacious in preventing ischemic/reperfusion induced myocardial injury both functionally and ultrastructurally. Isolated perfused rat hearts (n=8/group) were subjected to 30 minutes of global ischemia and 20 minutes of reperfusion. Histidine concentrations ranging from 10 to 50 mM were given throughout the experiment. During ischemia and reperfusion without histidine the contractile function and coronary flow were 59.+-.10% and 78.+-.6% of control, respectively. Perfusion with histidine (25 mM and above) resulted in significant increases in contractility (94.+-.4%) and coronary flow (92.+-.4) levels. The incidence of arrhythmias (ventricular tachycardia and ventricular fibrillation) during reperfusion was 100 percent (8/8) in the ischemic/reperfused group with an average duration of 13.23.+-.4.48 min. The addition of 25 mM histidine to the perfusion medium reduced the incidence and duration of arrhythmias significantly (mean.+-.SEM 2.25.+-.0.98 min) (P<0.01). The protective effects of histidine (25 mM and 50 mM) were significantly better than SOD/catalase/mannitol. Histidine has also been found to significantly reduce the infarct size and the occurrence of arrhythmias in vivo.
REFERENCES:
patent: 4734276 (1988-03-01), Ziegler
Bolli et al., "Role of OXY-Radicals in Postischemic Myocardial Dysfunction," Singal, P.K., ed., Oxygen Radicals in the Pathophysiology of Heart Disease, Kluwer Publishers, (1988), pp. 203-225.
Burton et al., "Alterations in Membrane Phospholipids, Mechanisms of Free Radical Damage and Antioxidant Protection During Myocardial Ischemia and Reperfusion," Singal, P.K., ed., Oxygen Radicals in the Pathophysiology of Heart Disease, Kluwer Publishers, (1988), pp. 161-176.
Eugui et al., "Some antioxidants inhibit, in a co-ordinate fashion, the production of tumor necrosis factor-.alpha., IL-.beta., and IL-6 by human peripheral blood mononuclear cells," Int'l Immunol. 6(3):409-422 (1993).
Gebhard et al., "Bretschneider's Histidine-Buffered Cardioplegic Solution: Concept, Application, and Efficiency," Myocardial Protection in Cardiac Surgery, pp. 95-119 (1987).
Gebhard et al., Thorac. Cardiovasc. Surgeon, 32:271-276 (1984).
Grimble, "Malnutrition and the immune response 2. Impact of nutrients on cytokine biology in infection," Transactions of the Royal Society of Tropical Medicine and Hygiene 88:615-619 (1994).
Grimble, "Nutritional Antioxidants and the Modulation of Inflammation: Theory and Practice," New Horizons 2(2):175-185 (1994).
Kelly et al., "Dimethyl Sulfoxide Modulates NF-KB and Cytokine Activation in Lipopolysaccharide-Treated Murine Macrophages," Infect. Immun. 62(8) :3122-3128 (1994).
Kukreja et al., "Singlet Oxygen Interaction with Ca.sup.2+ -ATPase of Cardiac Sarcoplasmic Reticulum," American Heart Assoc., Circulation Supplement, Abstracts of the 63rd Scientific Sessions, vol. 82, No. 4, Nov. 12-15, 1990.
MacFarlane et al., "Rapid Communication Synergism of Histidyl Dipeptides as Antioxidants," J. Mol. Cell Cardiol. 23:1205-1207 (1991).
Schneider et al., "Protective Solutions for heat and kidneys" Chem. Abstr. 94(6):363498.
Shenkar et al., "Effects of treatment with the 21-aminosteroid, U74389F, on pulmonary cytokine expression following hemorrhage and resuscitation," Critical Care Medicine 23 (1) :132-139 (1995).
Yakushev et al., Issues in Medical Chemistry, pp. 476-478 (1976).
Hess Michael L.
Kukreja Rakesh C.
Angres Isaac A.
Cook Rebecca
CYTOS Pharmaceuticals, LLC
Petraglia Susan
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