Appreciation of trimetazidine treatment in experimental sepsis rat model.

INTRODUCTION: Our aim was to determine the efficacy of trimetazidine on experimental sepsis rat model. MATERIAL AND METHODS: Sixty rats were randomized into three groups. In Group 1, sepsis was induced. In Group 2, sepsis was induced and as a therapeutic agent trimetazidine was given. In Group 3, rats were sham operated. Serum interleukin-1 beta (IL-1ß), tumor necrosis factor alfa (TNF-α), superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) and malondialdehyde (MDA) levels were determined in all groups. RESULTS: In Group 2, serum GSH-Px and SOD levels were statistically significantly higher than in Group 1 (p< 0.05) and serum MDA levels were statistically significantly lower than in group 1 (p < 0.05). Trimetazidine also significantly decreased the levels of IL-1ß and TNF-a which are the proinflammatory cytokines (p < 0.05). CONCLUSION: Trimetazidine treatment significantly improved inflammation, oxidative stress and membrane destruction in LPS-induced sepsis. As the proinflammatory cytokines are supposed to play a primary role in the pathogenesis of sepsis, we assumed that the trimetazidine treatment would give new insights into the treatment of sepsis (Tab. 1, Fig. 5, Ref. 29).

The effects of glycyrrhizin on experimental acute pancreatitis in rats.

INTRODUCTION: Although physiopathology of acute pancreatitis (AP) is not fully understood, the roles of reactive oxygen species (ROS) and changes of cytokines have been determined. AIM: To investigate anti-inflammatory and anti-oxidant effects of glycyrrhizin (GL) on taurocholate-induced AP in rats. MATERIALS AND METHODS: Thirty six rats were randomly divided into three groups as sham, AP and AP+GL (n=12 per group). AP was induced by 1 ml/kg body weight using 5% taurocholate injection into the biliopancreatic duct in groups II and III after clamping the hepatic duct. In groups III, GL (20 mg/kg) was given by oral gavage twice daily for 4 days. Group I and II did not receive any treatment. After the rats were killed; blood samples were taken to measure amylase, lipase, calcium, albumin, urea, glucose, AST and LDH assays before killing. Pancreatic tissue samples were also taken for biochemical analyses and histopathology. RESULTS: Amylase, lipase, AST and urea levels were significantly lower in the AP+GL group than in the AP group. Cytokines including IL-6, TNF-α and MPO levels were significantly lower in the AP+GL group than in the AP group. Even so there is no statistically difference between in the AP+GL group and the AP group in terms of pancreatic tissue IL-1ß, IL-6 and TNF-α levels. DISCUSSION: GL treatment significantly decreased pancreatic tissue MPO activities and MDA levels in the AP+GL group compared with the other groups (p = 0.001 and p = 0.05, respectively). Acinar cell necrosis, hemorrhage, and edema determined that were significantly lower in the AP+GL group than in the AP group (p < 0.001). CONCLUSIONS: GL treatment for acute necrotizing pancreatitis in rats suppressed the levels of pro-inflammatory cytokines, and caused a clear recovery of histological changes.

Comparison of F18-FDG PET/CT findings with current clinical disease status in patients with Takayasu's arteritis.

OBJECTIVES: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG PET/CT) scanning has been proposed as a new tool to assess disease activity in Takayasu Arteritis (TA). We investigated whether F-18 FDG PET/CT findings were consistent with current clinical disease status in patients with TA. METHODS: In this cross-sectional study, 22 patients with TA were enrolled. Clinical disease activity was assessed by the combination of National Institutes of Health (NIH) criteria, Disease Extent Index-Takayasu (DEI-Tak) score, physician global assessment and F-18 FDG PET/CT scans. RESULTS: At the time F-18 FDG PET/CT scans were taken, the majority of the patients (17/22) were using immunosuppressive (IS) drugs, and only four patients had clinically active disease. F-18 FDG PET/CT scans confirmed the presence of active vasculitic lesions in those four patients. In 16 out of 18 patients who were accepted to be in clinical remission, F-18 FDG PET/CT scans were also normal. There were only two patients with discordant results, i.e. active F-18 FDG PET/CT findings despite the lack of clinical activity. Interestingly, clinical exacerbation occurred four weeks later in one of them. Overall sensitivity and specificity of F-18 FDG PET/CT findings for clinical activity were 100% and 88.9%, respectively. CONCLUSIONS: We found that F-18 FDG PET/CT findings were generally consistent with clinical disease status in TA. Although use of IS drugs certainly impairs diagnostic accuracy of F-18 FDG PET/CT in TA, this imaging method may still have a potential for confirming remission or detecting disease activity in patients with TA receiving treatment.

FcgammaRIIa, IIIa and IIIb gene polymorphisms in Behçet's disease: do they have any clinical implications?

OBJECTIVE: Behçet's disease (BD) is a unique systemic vasculitis involving both arteries and veins of all sizes. Since Fcgamma receptors (FcgammaR) are important in mediating various immune effector functions, FcgammaR gene polymorphisms may affect the susceptibility to systemic inflammatory diseases such as BD. The aim of this study was to show the distribution of FcgammaRIIa, IIIa ve IIIb receptor gene polymorphisms in BD, and to investigate possible genotype-phenotype relationships. METHODS: In this cross-sectional study, FcgammaRIIa (H/H131, H/R131, R/R131), IIIa (F/F158, F/V158, V/V158), and IIIb (NA1/NA1, NA1/NA2, and NA2/NA2) receptor gene polymorphisms were investigated in 216 unrelated Turkish BD patients (M/F: 130/86) and in 241 healthy subjects, using an allele-specific polymerase chain reaction. RESULTS: The FcgammaRIIa R/R131 (p=0.019) and FcgammaRIIIa F/F158 genotypes (p=0.001) were found to be significantly more frequent in BD compared with healthy controls, whereas the FcgammaRIIIb genotypes were not (p=0.108). Allele analysis showed that the FcgammaRIIIa 158 (p=0.001) and FcgammaRIIIb NA2 (p=0.016) alleles were more frequent in BD than in healthy controls. In BD patients the FcgammaRIIIa V/V158 genotype was significantly associated with the presence of arthritis (p=0.002) and with an earlier disease onset (p=0.008), while the FcgammaRIIIb NA2/NA2 genotype was significantly associated with disease severity (p=0.02), vascular involvement (p=0.014), and pathergy positivity (p=0.02). CONCLUSION: We found that the genotype frequencies and allelic distributions of the FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb gene polymorphisms were significantly different between BD patients and healthy controls. In addition, certain FcgammaRIIIa and FcgammaRIIIb gene polymorphisms appear to be associated with an early disease onset, disease severity, the presence of arthritis, and vascular involvement in BD.

Efficacy of deferoxamine, N-acetylcysteine and selenium treatments in rats with Adriamycin-induced nephrotic syndrome.

BACKGROUND: Various experimental models related to Adriamycin (ADR)-induced nephropathy have been reported. The purpose of the present study was to evaluate the efficacy of N-acetylcysteine (NAC), deferoxamine (DFO) and selenium in protection against renal injury in ADR nephropathy. METHODS: The study included 53 Sprague Dawley male rats. Nephrotic syndrome was induced by injection of ADR 5 mg/kg intravenously (n=46). Control rats (n=7) were injected with an equal volume of isotonic saline. After ADR administration, they were divided into a group given only ADR (n=17) and 3 antioxidant treatment groups: (i) NAC (n=10), (ii) DFO (n=10) and (iii) selenium (n=9). In both renal tissue and erythrocytes, oxidative system parameters and trace elements were determined. RESULTS: Nephrotic syndrome was proven in ADR-injected rats 4 weeks after injections, with proteinuria, higher blood lipids and hypoalbuminemia. All of the antioxidant agents used in the present study to prevent the development of nephrotic syndrome provided benefits for the nephrotic state. Of them, selenium seemed to offer relatively lower and statistically insignificant efficacy for preventing proteinuria compared with the others. CONCLUSIONS: Our results showed that concomitant administration of some antioxidants with ADR injections seems to have beneficial effects on clinical parameters even if antioxidants were given in a single dose. NAC and DFO are more effective than selenium to prevent renal injury.

Detrimental effects of N-acetylcysteine plus desferoxamine combination in an experimental nephrotic syndrome model.

The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) and desferoxamine (DFO) administered alone or in combination together in rats with doxorubicin (DOX)-induced nephrotic syndrome, by monitoring oxidative stress parameters and trace elements in renal tissue and erythrocytes. Fifty-four male Sprague-Dawley rats were included the study. Equal volume of isotonic saline was injected to control rats. After DOX administration, the animals were divided into four experimental groups: (a) rats given only DOX; (b) rats treated with NAC; (c) rats treated with DFO; (d) rats treated with NAC plus DFO. The combination of N-acetylcysteine and DFO has no beneficial effect on reducing proteinuria in experimentally nephrotic rats, although both of these agents ameliorate the condition when administered separately. It seems likely that detrimental effects of NAC plus DFO could be secondary to its effects on erythrocyte selenium levels demonstrated here. Consequently, the results may propose caution to the use of antioxidant therapeutic strategies such as NAC plus DFO against nephropathy.

Pulmonary hypertension in rheumatoid arthritis.

Using Doppler echocardiography (DE), we measured pulmonary arterial systolic pressure (PASP) in rheumatoid arthritis (RA) patients without coexisting cardiopulmonary diseases. Accepting the normal upper limit of PASP as 30 mmHg, we found elevated PASP in 11 out of 40 (27.5%) RA patients, values being mostly 30-40 mmHg, indicating mild pulmonary hypertension (PHT). Although estimation of PASP by DE is not as reliable as cardiac catheterisation, it is possible that mild elevations in PASP may contribute to the high incidence of cardiovascular events not explained by traditional cardiac risk factors in patients with RA. Long-term follow-up will be obviously necessary to ascertain the impact of mild PHT on the prognosis and mortality rate of RA patients.