Possible scavenger effect of salicylic acid on nitric oxide production in vitro

J Mol

Cell

Cardiol

24 (Supplement

I) (1992)

0-1@7EFFECTS OF POLYETHYLENE GLYCOL CONJUGATED SUPEROXIDE DISMUTASE UPON COXSACKIEVIRUS B3 MYOCARDITIS IN MICE Yuji Hiraoka, Chiharu Kishimoto, Shigetake Sasayama. Toyama Medical & Pharmaceutical University, Toyama, Japan glycol conjugated superoxide TO test the therapeutic efficacy of polyethylene coxsackievirus dismutase (PEG-SOD), a potent scavenger of oxygen free radicals, upon B3 (CB3) myocarditis, C3H/He mice were inoculated with CB3. PEG-SOD was administered Grp 1 was an infected control. The severity of myocardial daily SC on days O-14. Score lesions in Grp 2 PEG-SOD Survivors Myocard. Lesion GrP cl+ to 4+1 was significantly INF N C lower compared to (U/kg/day) (n) (n) 1.7to.7 1 37 29 2.5ro.9 2.4to.9 Grp 1. However, 2 1x;03 36 30 2.oto.9* 1.9?0.8* 1.420.5* that of high dose 3 1x104 35 25 2.3f0.8 2.2tO.8 1.5f0.6 of PEG-SOD(Grp 4) 4 1~10~ 25 lO* 3.0+1.0* 3.1+0.8* 2.4iO.7* was paradoxically The *P
0-1()-8POSSIBLB SCAVENGER KFPECT OF SALICYLIC ACID ON NITRIC OXIDE PRODUCTION IN VITRO Giovanni Cavallo,Maria A.Chessa,Valter* -'ensa,Marco Tubaro*,Filippo Milazzotto',Ezio Tubaro-Wellcome Italia Research Labs and *CCU,S.Camillo Hospital-Rome(Italy) The possible scavenger effect of salicylic acid (SA) on nitric oxide (NO) was studied in vitro. Three studies were conducted: (1) glycerol trinitrate (GTN) ZmM,L-cysteine (C) 5mM and SA 10 mM were incubated at 41°C for l-10-20-30-60 min: nitrite pro(2) GTN 2mM and C 5mM were duction was meausured by the calorimetric method of Green. incubated,in presence of oxyhemoglobin 2.5 mcM,with SA (2.5-5-10 mM): NO liberation was evaluated by the kinetic method of Feelish. (3) GTN 2mM,C 5mM and SA 1OmM were incubated at 41°C for 20 min: the reaction products of SA were extracted and analyzed by gas chromatography-mass spectrometry (GC-MS) for the presence of nitrosylated derivatives of SA. SA strongly inhibited nitrite production (80 mcM vs 260 mcM,p 0.0001) and NO liberation (0.196 vs 0.596 mcM/min,p 0.0001); GC-MS demonstrated the formation of two SA derivatives (ortho-nitroso-phenol and 2,4-dinitroso-phenol), possibly resulting from a SA reacts with NO, yielding medecarboxylation reaction of NO and SA. In conclusion, in vitro and possibly in viva. tabolites that can be used to evaluate NO production

o-11-1

CHANGE OF MHC CLASS 1 EXPRESSION ON HUMAN MYOCYTES DURING IMMUNOSUPPRESSION Izuru Nakamura, Christian Hengstenberg *, Manfred Hummel”‘, Roland Hetzer**, Bernhard Ma&h* Department of Internal Medicine, Aoto Hospital, Jikei University School of Mdicine, Tokyo, Japan. *Philipps University, Marburg, **German Heart Center, Berlin, Germany 217 sequential cardiac biopsies from 17 transplanted patients@1 males and 6 females,mean age:35.5*5.5 years) were examined using mouse monoclonal antibodies and the avidin-biotin immunoperoxidase technique. Changes of MHC class 1 expression on myocytes during immunosupression were investigated. The incidence of class 1 expression on myocytes was 17% in rejection grade of the modified Hannover classification AO(n=12), 30% in grades AltA2@=50), 75% in grade A3a(n=53), 82% in grades A3btA4(n=61), 79% in grade A5a(n=33), 25% in grade A5b(n=8). There was a significant correlation between mild rejection and moderate to severe rejection in class 1 expression on myocytes. In addition to basic immunosuppressive therapy, 7 patients received steroids in high dose, 5 patients received steroids and ATG/ALG, 3 patients steroids, ATG/ALG and OKT-3. If proved effective histologicaify, the reduction of class 1 antigen on myocytes was observed about 3 weeks after steroid therapy, about 2 weeks after ATG or OKT-3 therapy. Changes of class 1 expression on myocytes could be a useful marker of successful treatment of rejection. S.73