This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD50) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with 7-nitroindazole and decreased by pretreatment with L-arginine and fenbufen. The increase in nitric oxide (NO) production andmalondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD50 of ciprofloxacin in mice brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with L-arginine. The elevation induced by the clonic CD50 of ciprofloxacin in brain glutamate levelwas not changed by pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or L-arginine. Combined treatment of mice with fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate andMDA levels as well as inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD50 of ciprofloxacin produced an increase in inducible but not in neuronal NO synthasemRNA and protein expressions in mice brain. These results suggest that elevation of brain glutamate levelswith consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacininduced convulsive seizures.

This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD50) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with 7-nitroindazole and decreased by pretreatment with L-arginine and fenbufen. The increase in nitric oxide (NO) production andmalondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD50 of ciprofloxacin in mice brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with L-arginine. The elevation induced by the clonic CD50 of ciprofloxacin in brain glutamate levelwas not changed by pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or L-arginine. Combined treatment of mice with fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate andMDA levels as well as inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD50 of ciprofloxacin produced an increase in inducible but not in neuronal NO synthasemRNA and protein expressions in mice brain. These results suggest that elevation of brain glutamate levelswith consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacininduced convulsive seizures.

This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD50) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with 7-nitroindazole and decreased by pretreatment with L-arginine and fenbufen. The increase in nitric oxide (NO) production andmalondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD50 of ciprofloxacin in mice brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with L-arginine. The elevation induced by the clonic CD50 of ciprofloxacin in brain glutamate levelwas not changed by pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or L-arginine. Combined treatment of mice with fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate andMDA levels as well as inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD50 of ciprofloxacin produced an increase in inducible but not in neuronal NO synthasemRNA and protein expressions in mice brain. These results suggest that elevation of brain glutamate levelswith consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacininduced convulsive seizures.

Purpose: To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify prognostic and predictive value of the biomarkers ;p53, pRB, BCL2 and EGFR. Patients and Methods: Between 2000 and 2006, a total of 55 patients with T2-T3 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From September 2000 to May 2003, 25 patients (in protocol no. 1) were treated by TURBT followed by radiotherapy 46 Gy with concurrent cisplatin 20 mg/m² day1-5, followed for complete and partial responders by radiotherapy 20 Gy with concurrent cisplatin (same dose) on the last five days. From December 2004 to April 2006, thirty patients were entered in protocol no. 2 that consisted of radiotherapy 60 Gy with concurrent Cisplatin 75 mg/ m2 q. 3 ws and Gemcitabine 300 mg / m2 D 1, 8 and 15 q. 3 ws for 2 cycles. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. All specimens were examined for expression of the biomarkers (p53, bcl2, Rb and EGFR) using immunohistochemical staining. Results: The median follow-up for all patients is 30 months (range 4–84), 38 months (range 9– 84) for patients in P1 and 22 months (4–54) for patients in P2. The actuarial 5-year OS were 58 % (SE 5), 52% (SE 7) and 61% (SE 6),for the whole series, P1 and P2 protocols respectively, (P =0.270). The corresponding figures for cancer specific survival (CSS) were 60%, 55% (SE 7) and 63% (SE 4), (P = 0.452). The 5-year actuarial OSB for all series, P1 and P2 protocols were 51% (SE 6), 46% (SE 7) and 55% (SE 9), respectively, (P = 0.323). For all patients, altered expression of p53, bcl2, pRb and EGFR were detected in (47.3%, 56.4%, 52.7% and 40% respectively The results of UVA showed that tumor stage and altered expression of pRB, BCL2 and EGFR were significantly associated with CSS and OS (P0.05). There were no grade 4 toxicity and no treatmentrelated deaths. Conclusion: Trimodality therapy to preserve the bladder is a therapeutic option that results in a high rate of long-term survivors retaining functional bladders in carefully selected patients. Patients with higher tumour stage and altered biomarkers; pRB, BCL2 and EGFR might not be candidate for bladder preserving approach.

Purpose: To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify prognostic and predictive value of the biomarkers ;p53, pRB, BCL2 and EGFR. Patients and Methods: Between 2000 and 2006, a total of 55 patients with T2-T3 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From September 2000 to May 2003, 25 patients (in protocol no. 1) were treated by TURBT followed by radiotherapy 46 Gy with concurrent cisplatin 20 mg/m² day1-5, followed for complete and partial responders by radiotherapy 20 Gy with concurrent cisplatin (same dose) on the last five days. From December 2004 to April 2006, thirty patients were entered in protocol no. 2 that consisted of radiotherapy 60 Gy with concurrent Cisplatin 75 mg/ m2 q. 3 ws and Gemcitabine 300 mg / m2 D 1, 8 and 15 q. 3 ws for 2 cycles. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. All specimens were examined for expression of the biomarkers (p53, bcl2, Rb and EGFR) using immunohistochemical staining. Results: The median follow-up for all patients is 30 months (range 4–84), 38 months (range 9– 84) for patients in P1 and 22 months (4–54) for patients in P2. The actuarial 5-year OS were 58 % (SE 5), 52% (SE 7) and 61% (SE 6),for the whole series, P1 and P2 protocols respectively, (P =0.270). The corresponding figures for cancer specific survival (CSS) were 60%, 55% (SE 7) and 63% (SE 4), (P = 0.452). The 5-year actuarial OSB for all series, P1 and P2 protocols were 51% (SE 6), 46% (SE 7) and 55% (SE 9), respectively, (P = 0.323). For all patients, altered expression of p53, bcl2, pRb and EGFR were detected in (47.3%, 56.4%, 52.7% and 40% respectively The results of UVA showed that tumor stage and altered expression of pRB, BCL2 and EGFR were significantly associated with CSS and OS (P0.05). There were no grade 4 toxicity and no treatmentrelated deaths. Conclusion: Trimodality therapy to preserve the bladder is a therapeutic option that results in a high rate of long-term survivors retaining functional bladders in carefully selected patients. Patients with higher tumour stage and altered biomarkers; pRB, BCL2 and EGFR might not be candidate for bladder preserving approach.

Abstract Background: Bladder cancer is one of the commonest malignancies among Egyptian population with high morbidity and mortality rates. Human epidermal growth factor receptor-2 (Her-2/Neu) seems to play role in the pathogenesis and prognosis of bladder carcinomas; however, its expression and prognostic significance were variable between different studies. This study evaluates the status of Her-2/Neu protein expression in invasive carcinomas of the bladder among a cohort of Egyptian patients using immunohistochemistry (IHC) and determines its relation to some clinicopathological factors. Methods: A number of 32 invasive bladder carcinoma patients treated with radical cystectomy were enrolled. Tumor sections were immunostained using anti-Her-2/Neu antibody and were evaluated by at least two pathologists. Statistical analysis was carried out with the Statistical Software Package Standard (SPSS). Results: Her-2/Neu membranous staining was observed in 20 carcinomas (62.5%). Statistical analysis revealed significant direct association between Her-2/Neu and both increasing grade of carcinoma (P = 0.001) and depth of tumor invasion (P ≤ 0.001). Patient’s gender, histological subtype and the presence of bilharzial cystitis did not have any significant association with Her-2/Neu overexpression. Conclusion: Her-2/Neu immunopositivity was observed in a considerable proportion of cases with association to adverse prognostic factors, thus patients with high-grade, deeply invasive carcinoma of the bladder may benefit from Her-2/Neu-targeted therapies after radical cystectomy.

Abstract: Objective: The study aimed to examine the effect of exogenous OT administration on the inflammation and atherosclerosis in adult male rats and its possible mechanisms. Thirty adult male rats equally divided into three groups. Control group fed regular diet; group II fed control diet supplemented with L-methionine for 10 weeks. Group III received L-methionine and oxytocin treatment for 10 weeks. RT-PCR analysis showed that OT administration increased oxytocin receptor mRNA (2 fold, P, 0.05). Blood samples were evaluated for total homocysteine, interlukin-6 (IL-6), monocyte chemoatrratant protein-1 (MCP-1) and C-reactive protein (CRP) by ELIZA. lipid profile, nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) were determined. Specimens from aorta were processed for immunohistochemical staining for Aorta nuclear factor _B (NF-κB) p65 protein. Result showed that OT administration to group III decreased the plasma levels IL-6, MCP-1and CRP levels which were elevated in group II. Moreover, there was decrease of the oxidative stress of group III in terms of increased plasma levels of NO and GSH and decreased plasma levels of MDA in blood. In addition, rats of group II showed histological abnormalities manifested by thickening and ulceration of the aortic wall. Marked increased expression of NF-κB in aorta of in group II was detected. However, OT administration restores the histological structure of the aorta and decreased the expression of NF-κB in aorta of group III similar to the control group. Conclusion: OT has anti inflammatory pathway in atherosclerosis as it decelerates atherosclerosis by decreasing the proinflammatory responses through many mechanisms, mainly the up regulation of its receptors.

Abstract: Objective: The study aimed to examine the effect of exogenous OT administration on the inflammation and atherosclerosis in adult male rats and its possible mechanisms. Thirty adult male rats equally divided into three groups. Control group fed regular diet; group II fed control diet supplemented with L-methionine for 10 weeks. Group III received L-methionine and oxytocin treatment for 10 weeks. RT-PCR analysis showed that OT administration increased oxytocin receptor mRNA (2 fold, P, 0.05). Blood samples were evaluated for total homocysteine, interlukin-6 (IL-6), monocyte chemoatrratant protein-1 (MCP-1) and C-reactive protein (CRP) by ELIZA. lipid profile, nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) were determined. Specimens from aorta were processed for immunohistochemical staining for Aorta nuclear factor _B (NF-κB) p65 protein. Result showed that OT administration to group III decreased the plasma levels IL-6, MCP-1and CRP levels which were elevated in group II. Moreover, there was decrease of the oxidative stress of group III in terms of increased plasma levels of NO and GSH and decreased plasma levels of MDA in blood. In addition, rats of group II showed histological abnormalities manifested by thickening and ulceration of the aortic wall. Marked increased expression of NF-κB in aorta of in group II was detected. However, OT administration restores the histological structure of the aorta and decreased the expression of NF-κB in aorta of group III similar to the control group. Conclusion: OT has anti inflammatory pathway in atherosclerosis as it decelerates atherosclerosis by decreasing the proinflammatory responses through many mechanisms, mainly the up regulation of its receptors.

Abstract: Objective: To evaluate the diagnostic role of gastrointestinal endoscopy and biopsy in children with recurrent abdominal pain (RAP). Patients and methods: Fifty children with RAP were included, their ages ranged from 3 to 15 years. All patients were subjected to detailed history, examinations, routine investigations, IgG for H. pylori, upper and lower endoscopy and biopsy. Antigliadin antibodies and indirect hemagglutination test for amebiasis. RESULTS: The endoscopic findings were abnormal in 34 cases. Erythematous mucosa, nodular mucosa then ulceration and oedema, were strongly associated with presence of histopathological findings with sensitivity 94.3%, specificity 93.3%,, positive predictive value (PPV)=97.1% and negative predictive value (NPV) = 87.5%. H. pylori infection was diagnosed in 15 patients serum IgG for H. Pylori was positive in 11 patients with sensitivity 73.3%. Endoscopic findings were positive in 13 patients with H. pylori infections with sensitivity 86.7%, while histopathological findings were positive in all patients with H. pylori infections with specificity 100%, PPV=100% and NPV =94.6%. Parasitic infestations were diagnosed in 9 patients. Four patients for each GE reflux disease and gastrodudenitis .Two patients were diagnosed for each of celiac disease, ulcerative colitis, chronic non specific colitis, duodenal ulcer and infected juvenile polyp .No etiology identified in 8 patients. Conclusions: Pediatric gastrointestinal endoscopy is a valuable and informative diagnostic procedure even in young children and can be used safely with the use of intravenous sedation.