p53 antibodies, metallothioneins, and oxidative stress markers in chronic ulcerative colitis with dysplasia.

AIM: To investigate the role of p53 antibodies (p53Abs), metallothioneins (MTs) and oxidative stress markers in the early detection of dysplasia in chronic ulcerative colitis (UC). METHODS: The study included 30 UC patients, 15 without dysplasia (group II) and 15 with dysplasia (group III), in addition to 15 healthy volunteers (group I, control subjects). The enzyme-linked immunosorbent assay technique was used to measure serum p53Abs and MTs, while advanced oxidation protein products (AOPPs), and reduced glutathione (GSH) levels were measured by spectrophotometric method in all subjects. RESULTS: In group II and group III compared to group I, there were significant increases in serum levels of AOPPs (145.94 ± 29.86 µmol/L and 192.21 ± 46.71 µmol/L vs 128.95 ± 3.06 µmol/L, P < 0.002 and P < 0.001, respectively), MTs (8.18 ± 0.35 µg/mL and 9.20 ± 0.58 µg/mL vs 6.12 ± 0.25 µg/mL, P < 0.05 and P < 0.05, respectively), and p53Abs (20.19 ± 3.20 U/mL and 34.66 ± 1.34 U/mL vs 9.42 ± 1.64 U/mL, P < 0.001 and P < 0.001, respectively). There were significantly higher levels of AOPPs (P < 0.05) and p53Abs (P < 0.001) in UC patients with dysplasia compared to those without dysplasia, while MTs showed no significant difference between the 2 groups (P > 0.096). In contrast, GSH levels showed a significant decrease in both patients' groups (1.87 ± 0.02 µmol/mL and 1.37 ± 0.09 µmol/mL vs 2.49 ± 0.10 µmol/mL, P < 0.05 and P < 0.05 in groups II and III, respectively) compared with group I, and the levels were significantly lower in group III than group II (P < 0.05). There was a positive correlation between AOPPs and both MTs (r = 0.678, P < 0.001) and p53Abs (r = 0.547, P < 0.001), and also between p53Abs and MTs (r = 0.739, P < 0.001). There was a negative correlation between AOPPs and GSH (r = -0.385, P < 0.001), and also between GSH and both MTs (r = -0.662, P < 0.001) and p53Abs (r = -0.923, P < 0.001). CONCLUSION: Oxidative stress and oxidative cellular damage play an important role in the pathogenesis of chronic UC and the associated carcinogenetic process. p53Abs levels could help in early detection of dysplasia in these conditions.

Effect of atorvastatin on inflammation and modification of vascular risk factors in rheumatoid arthritis.

OBJECTIVE: To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment. RESULTS: Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001). CONCLUSION: Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function.

Genetic polymorphism of glutathione S-transferases M1 and T1 in Egyptian patients with bilharzial bladder cancer.

OBJECTIVE: To assess the influence of glutathione S-transferases M1 and T1 (GSTM1 and T1) genotype on the risk of bladder cancer in patients with urinary bilharziasis. MATERIALS AND METHODS: This study was designed as a case-control study that involved 60 individuals who were enrolled into 3 equal groups. The first one included patients with bilharzial bladder cancer, the second one had those with nonmalignant urinary bilharziasis, and the last one was the control group. All of the participants were adult males, nonsmokers, and with matched ages. All of them underwent an assessment of the serum level of the total GST concentration and the polymerase chain reaction (PCR) was used for determination of the GSTM1 and T1 genotypes. RESULTS: The lower most GST enzyme concentration was reported in patients with bilharzial bladder cancer (26 +/- 4.4 ng/ml) with significant difference between it and that of the second group (36.8 +/- 4.1 ng/ml, P < 0.05) and that of the controls (40.4 +/- 4 ng/ml, P < 0.005). The PCR results have demonstrated that the frequency of combined GSTM1 and T1 genes deletion (M1-ve T1-ve) was significantly higher in cases of bladder cancer (40%) than those of the controls (5%, P < 0.005) and those of the second group (10%, P < 0.05). The unconditional logistic regression test revealed that patients with urinary bilharziasis and combined GSTM1 and T1 genes deletion are at a significant risk for malignant transformation (OR = 6.3, P < 0.05). CONCLUSIONS: Patients with urinary bilharziasis and GSTM1-ve and T1-ve genes might be at increased risk of bladder cancer. However, larger studies are needed for confirmation of these results.

Food additives and Hymenolepis nana infection: an experimental study.

The effect of sodium benzoate (SB) on the pathogenesis of Hymenolepis nana (H. nana) and its neurological manifestations was studied in the present work. One hundred and thirty five mice were classified into three groups. GI: received SB alone. GII: received SB before & after infection with H. nana and GIII: infected with H. nana. All groups were subjected to parasitological, histopathological, immunohistochemical and biochemical assays. The results revealed a significant decrease in IL-4 serum level with a significant increase in gamma amino butyric acid (GABA) and decrease in zinc brain levels in GI, while GII showed non significant increase in IL-4 level that resulted in a highly significant increase in the mean number of cysticercoids and adult worms with delayed expulsion as compared to GIII. This was reflected on histopathological and immunohistochemical changes in the brain. Also, there was a highly significant increase in GABA and decrease in zinc brain levels in GII to the degree that induced behavioral changes. This emphasizes the possible synergistic effect of SB on the neurological manifestations of H. nana and could, in part, explain the increased incidence of behavioral changes in children exposed to high doses of SB and unfortunately have H. nana infection.

Mechanism of the neuroprotective role of coenzyme Q10 with or without L-dopa in rotenone-induced parkinsonism.

Current treatment options for parkinsonism as a neurodegenerative disease are limited and still mainly symptomatic and lack significant disease-modifying effect. Understanding its molecular pathology and finding the cause of dopaminergic cell loss will lead to exploring therapies that could prevent and cure the disease. Mitochondrial dysfunction was found to stimulate releasing of reactive oxygen species (ROS) with subsequent induction of apoptotic neuronal cell death. The aim of the present study was to throw the light on the role of coenzyme Q10 with or without L-dopa in an experimental model of parkinsonism induced by rotenone in rats. The present work showed that rotenone (2.5 mg/kg/day i.p. for 60 days) induced a model of parkinsonism (group II) resembling the basic findings in human characterized by bradykinesia and rigidity manifested as an increase in catalepsy score (detected after 20 days with bad prognosis after 60 days) with marked decrease in striatal dopamine levels. This model confirmed the implication of mitochondrial-apoptotic pathway in the pathogenesis of parkinsonism as there was a decrease in levels of striatal complex I activity and ATP as well as extreme overexpression of the antiapoptotic protein Bcl-2, and also exhibited the role of coenzyme Q10 where its plasma and striatal levels were found to be decreased in comparison to the normal control rats (group I). This proposed pathogenesis was evidenced by the significant correlation between catalepsy score and the neurochemical parameters obtained in the current work. The treated groups started to receive the drug(s) after 20 days from induction of parkinsonism and continued to complete for 60 days. Oral administration of Co Q10 in a low dose 200 mg/kg/day (group III) or a high dose 600 mg/kg/day (group IV), resulted in amelioration of the mitochondrial induced apoptosis by dose-dependent restoration of striatal complex I activity, ATP levels with temperate increase in expression of Bcl-2 as well as decrease in catalepsy score. Although both low and high doses of Co Q10 resulted in significant increase in its plasma and striatal levels, but only the high dose was shown to reach the recommended therapeutic levels. As a current replacement therapy, oral administration of levodopa 10 mg/kg/day (group V), caused symptomatic improvement in the form of reduction of catalepsy score with restoration of striatal dopamine levels, but it did not show any significant effects on either striatal complex I activity, ATP levels or the expression of Bcl-2, pointing to the lack of its disease-modifying role. On the other hand, its administration with high dose of coenzyme Q10 caused the most marked symptomatic improvement in catalepsy score when compared to its administration with low dose of coenzyme Q10, or when compared to either coenzyme Q10 high dose or L-dopa, respectively. Moreover, administration of high dose coenzyme Q10 with L-dopa provided a significant increase in striatal complex I activity, ATP levels and Bcl-2 expression in comparison to group administered coenzyme Q10 low dose with L-dopa, in addition to the significant restoration of striatal dopamine levels and both plasma and striatal Co Q10 levels. Regarding that L-dopa is viewed as a replacement therapy in parkinsonism, it could be concluded that addition of coenzyme Q10 in a high dose in early parkinson's disease could be recommended based on its proved disease-modifying role on several levels of the proposed mechanisms, including improvement of respiratory chain activity and intervention with neuronal apoptosis. A further research to investigate other apoptosis-targeted compounds will open a new era in the treatment of parkinsonism.

Genetic polymorphism of glutathione-S-transferase (GST-M1 and GST-T1) in schistosomiasis -associated bladder cancer in Egyptian patients.

This work was carried out on three groups, 30 Egyptian patients with Schistosoma haematobium (S. haematobium) with bladder cancer (15), and without bladder cancer (15), as well as 15 normal individuals as a control. All the individuals were subjected to measurement of serum level of GST by using ELISA technique and genotyping for GST-M1 & GST-T1 using PCR technique. The results proved that GST serum level was significantly deceased in S. haematobium patients with bladder cancer as compared to the other groups. The PCR results for the GST-M1 & GST-T1 genotyping showed 4 categories, (M1+ve/T1+ve, M1+ve/T1-ve, M1-ve/T1+ve, M1-ve/T1/-ve). There was a significant decrease in enzyme levels in patients with GST-M1-ve/T1-ve as compared to the other categories. Besides, there was a significant increased risk for bladder cancer development in patients with combined gene deletion (OR = 40) which represented mainly in S. haematobium patients with bladder cancer (53.3% = M1-ve/TI-ve).