The present study was carried to explore the potential antihyperglycemic and antihyperlipidemic activity of Ferula assa-foetida L. and Ferula tenuissima Hub-Mor & Pesmen extracts in streptozotocin (STZ) induced diabetic rats. Furthermore, phytochemical screening, in vitro antioxidant activity and acute toxicity study of both plants were performed. Both extracts showed considerable antioxidant potential in vitro. In diabetic rats, F. assa-foetida (200 and 400 mg/kg) and F. tenuissima (400 mg/kg) showed significant elevation in plasma insulin level, total hemoglobin (Hb) and decrease in Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) levels. Significant elevations in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and level of reduced glutathione (GSH) in liver and pancreas homogenates were observed in diabetic animals following F. assa-foetida (200 and 400 mg kgG1) and F. tenuissima (400 mg kgG1) treatments. The antihyperlipidemic effect of F. assa-foetida extract was demonstrated by a significant reduction in plasma triglycerides (TG), Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDL-C) and the increase of High Density Lipoprotein Cholesterol (HDL-C). Plasma activities of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and levels of Total Protein (TP) and bilirubin (BIL) in diabetic rats were recovered significantly after F. assa-foetida and F. tenuissima treatment in comparison with diabetic controls. The present data suggest that F. assa-foetida have both antihyperglycemic and antihyperlipidemic effects with enhancement of insulin-secreting activity.

In the present study, DPPH radical scavenging assay and ferric-reducing antioxidant assay were used to estimate the potential in vitro antioxidant effect of the methanol extracts of Ferula drudeana Korovin (F. drudeana) and Ferula huber-morathii Peşmen (F. huber-morathii). The antidiabetic activity of both extracts was evaluated in streptozotocin (STZ)-induced diabetic rats. Glibenclamide was taken as the standard drug. Both extracts showed considerable antioxidant potential in the DPPH radical scavenging assay and minimum reducing power in ferric-reducing antioxidant assay. Oral administration of F. drudeana (400 mg/kg) and F. huber-morathii (200 and 400 mg/kg) extracts to diabetic rats produced a marked reduction in Fasting Blood Glucose (FBG) and elevation in insulin levels after 14 and 28 days of treatment. A meaningful reduction in the concentrations of glycosylated hemoglobin (HbA1c), triglycerides (TG), Total Cholesterol (TC), Low Density Lipoprotein (LDL) in plasma and elevations in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH) in liver and pancreas homogenates were observed in diabetic animals medicated with F. drudeana (200 and 400 mg kgG1) and F. huber-morathii (400 mg kgG1) extracts. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, total protein and High Density Lipoprotein (HDL) in plasma and malondialdehyde (MDA) in liver and pancreas homogenates were recovered significantly in F. drudeana and F. huber-morathii-medicated diabetic rats. Besides, biochemical results were supported by histopathological findings. These findings showed the significant antioxidant and hypoglycemic activities of F. drudeana and F. huber-morathii extracts in diabetic rats.

In the present study, DPPH radical scavenging assay and ferric-reducing antioxidant assay were used to evaluate in vitro antioxidant potential of the methanol extract of Ferula duranii (F. duranii). The antihyperglycemic and antihyperlipidemic activities of F. duranii extract were evaluated in streptozotocin (STZ)-induced diabetic rats. F. duranii showed considerable antioxidant potential in the DPPH radical scavenging assay and minimum reducing power in ferric-reducing antioxidant power assay. A meaningful reduction in the concentrations of Fasting Blood Glucose (FBG), glycosylated hemoglobin (Hb A1c), triglycerides (TG), Total Cholesterol (TC) and Low Density Lipoprotein (LDL-C) in plasma and an elevation in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) in hepatic and pancreas homogenates were observed in diabetic animals medicated with F. duranii extract in comparison with diabetic control rats. The level of insulin raised significantly in plasma of diabetic groups received F. duranii in respect to diabetic control one. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, total protein and High Density Lipoprotein (HDL-C) in plasma and malondialdehyde (MDA) in liver and pancreas homogenates were recovered significantly in F. duranii-medicated diabetic rats in comparison with diabetic controls. The present data suggest that F. duranii has both antidiabetic and antihyperlipidemic effects.

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This study was designed to investigate the prevalence of metallo-β-lactamases (MBL) and extended-spectrum β -lactamases (ESBL) in P. aeruginosa isolates collected from two different hospitals in Cairo, Egypt. Antibiotic susceptibility testing and phenotypic screening for ESBLs and MBLs were performed on 122 P. aeruginosa isolates collected in the period from January 2011 to March 2012. MICs were determined. ESBLs and MBLs genes were sought by PCR. The resistant rate to imipenem was 39.34%. The resistance rates for P. aeruginosa to cefuroxime, cefoperazone, ceftazidime, aztreonam, and piperacillin/tazobactam were 87.7%, 80.3%, 60.6%, 45.1%, and 25.4%, respectively. Out of 122 P. aeruginosa, 27% and 7.4% were MBL and ESBL, respectively. The prevalence of bla(VIM-2), bla(OXA-10(-)), bla(VEB-1), bla(NDM(-)), and bla(IMP-1)-like genes were found in 58.3%, 41.7%, 10.4%, 4.2%, and 2.1%, respectively. GIM-, SPM-, SIM-, and OXA-2-like genes were not detected in this study. OXA-10-like gene was concomitant with VIM-2 and/or VEB. Twelve isolates harbored both OXA-10 and VIM-2; two isolates carried both OXA-10 and VEB. Only one strain contained OXA-10, VIM-2, and VEB. In conclusion, bla(VIM-2)- and bla(OXA-10)-like genes were the most prevalent genes in P. aeruginosa in Egypt. To our knowledge, this is the first report of bla(VIM-2), bla(IMP-1), bla(NDM), and bla(OXA-10) in P. aeruginosa in Egypt.

Importance: Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era.

Objective: To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone.

Design, Setting, and Participants: A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients from December 2002 to July 2008. Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic center. Patients with bladder cancer 70 years or younger having 1 or more risk factors (≥pT3b, grade 3, or positive nodes) with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease.

Interventions: Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin.

Main Outcome and Measure: Locoregional recurrence-free survival.

Results: The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8 cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53; 95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61; 95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm.

Conclusions and Relevance: Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials.

Trial Registration: clinicaltrials.gov Identifier: NCT01734798.

To date, radical cystectomy has continued to be the treatment of choice for muscle-invasive bladder cancer. It is associated with a 5-year disease-free survival rate ranging from 27-55%. This outcome is significantly worse when reporting upon locally advanced cases. The independent prognostic factors include: tumor stage, grade, pelvic nodal involvement and some other additional factors. Beside the higher reported incidence of distant metastasis, local recurrence either alone or combined with systemic relapse has been shown to be experienced by 23-50% of locally advanced patients - a rate that was much more frequent than previously believed. Nonrandomized trials of preoperative radiotherapy have suggested improved survival rates. However, only one out of the six randomized preoperative trials in the literature published in English has proved to be significant. On the other hand, the only randomized trial and most retrospective studies dealing with postoperative radiotherapy revealed a significant increase in disease-free survival. Late complications of post operative radiotherapy, contrary to former belief, were acceptable and generally depended upon the volume of the irradiated normal tissues and the radiotherapy techniques used. Most of these adjuvant or neoadjuvant reports were performed in the 1970s and 1980s using conventional radiation techniques. Modern radiotherapy, delivering higher doses to the tumor while saving a significant amount of the surrounding normal structure, has not been rigorously tested. However, these techniques have already succeeded in improving treatment end results in other pelvic tumors.