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Redox equilibrium is altered due to elevation of reactive oxygen species (ROS) or inadequate antioxidant defense, therapeutic effects of natural antioxidant such as curcumin (CMN) have been investigated. The aim of this study was to investigate the beneficial effects of curcumin (a natural polyphenol) on oxidative status of lung and liver and assessment of level of interleukin-6 (IL-6) in rats against paraquat toxicity. Forty adult male wistar rats were divided into five groups with eight animals each as followed: Group 1: control, Group 2: rats received olive oil. Group 3: rats received curcumin (CMN) (200 mg/kg body weight in olive oil) orally. Group 4 (model group): rats were given a single oral dose of paraquat (PQ) 50 mg/kg body weight dissolved in distilled water intra-peritoneally (I.P) Group 5: rats received CMN orally daily for 10 days prior to PQ administration with the same previous doses and after PQ. After forty eight hours of PQ administration, rats were sacrificed and lung and liver tissues samples were examined for detection of biochemical parameters and histopathological changes. Significant histopathological changes had resulted from PQ administration in lung and liver tissues in addition to significant increase in malondialdehyde (MDA), and significant decrease of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR). However, treatment with CMN produced increasing antioxidant markers and depletion of MDA compared to the model group. Also there is significant increase in serum IL-6 after PQ administration compared to control group. However, the level of IL-6 significantly decreased in treated group with curcumin compared to the model group. Curcumin possesses remarkable protection of the altered lung and liver tissues in paraquat intoxicated rats and could reduce the damaging effect by increasing antioxidant activity and decreasing lipid peroxidation, oxidative stress and IL-6.

Objective To develop and evaluate zolmitriptan spanlastics (Zol SLs) as a brain-targeted antimigraine delivery system. Spanlastics (SLs) prepared using span 60: tween 80 (70:30%, respectively) gave the highest percentage of entrapment efficiency (EE%). Materials and methods A total of 60 adult male Wistar albino rats were divided into six groups (n=10 rats/group). Group 1 (Control) comprised rats serving as a negative control. Group 2 was treated with glyceryl trinitrate (NTG) and served as the positive control. Groups 3 (NTG+Zol com), Group 4 (NTG+Zol sol) and Group 5 (NTG+Zol SLs) received commercial zolmitriptan orally, zolmitriptan solution intranasally and Zol SLs F5 intranasally, respectively, 30 min before NTG. Group 6 (Zol SLs) comprised normal rats that received only Zol SLs intranasally. Results We found decreased Tmax, increased Cmax, AUC0-6, AUC0-∞ and ameliorated behaviour in rats (head scratching) treated with intranasal SLs compared to oral commercial zolmitriptan. Conclusion Our study substantiates the enhanced efficacy of Zol SLs in brain targeting for migraine treatment.

Graphical abstract, Highlights • Aluminium phosphide (AlP) affects many organs especially heart. • Antioxidant activities of Moringa was investigated after acute AlP intoxication. • Moringa preventive effects were determined histopathologically. • Moringa significantly re-equilibrates antioxidant parameters back near to their normal values., Background Moringa oleifera extract (Lam) has many antioxidant and protective properties. Objective: to investigate the antioxidant activities of Lam in counteracting the high oxidative stress caused by acute sub-lethal aluminium phosphide (AlP) intoxication in rat heart. These activities will be detected by histopathological examination and some oxidative stress biomarkers. Methods a single sub-lethal dose of Alp (2 mg/kg body weight) was administered orally, and Lam was given orally at a dose (100 mg/kg body weight) one hour after receiving AlP to rats. Results aluminium phosphide caused significant cardiac histopathological changes with a significant increase in malondialdehyde (MDA); lipid peroxidation marker; and a significant depletion of antioxidant enzymes (catalase and glutathione reductase). However, treatment with Lam protected efficiently the cardiac tissue of intoxicated rats by increasing antioxidants levels with slight decreasing in MDA production compared to untreated group. Conclusions This study suggested that Moringa oleifera extract could possibly restore the altered cardiac histopathology and some antioxidant power in AlP intoxicated rats, and it could even be used as adjuvant therapy against AlP-induced cardiotoxicity.

Mohamed A El Nabarawi,1 Mahmoud H Teaima,1 Rehab A Abd El-Monem,2 Nagla A El Nabarawy,3 Dalia A Gaber4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October, Egypt; 3National Egyptian Center of Environment and Toxicological Research (NECTER), Faculty of Medicine, Cairo University, Cairo, Egypt; 4Department of Quality Control, Holding Company for Biological Products and Vaccines, Cairo, Egypt Abstract: To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH) and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin® 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10) and raft system formula (FRS-11) were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K,100M 1:1) showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K,100M 1%/Precirol 2%) had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the Cmax of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The tmax was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative bioavailability of the MbH was 104.76 and 116.01% after oral administration of FT-10 and FRS-11, respectively, compared to marketed product. These results demonstrated that both controlled-released floating matrix tablet and raft system would be promising gastroretentive delivery systems for prolonging drug action. Keywords: GRDDS, Precirol®, Compritol®, HPMC, Na alginate

Nitrites are found in several forms; they are widely found in water resources and used as additives and preservatives for food and as a color source. We investigated the hazardous effects of exposing rats to different doses of nitrites. Moreover, we examined such impacts, after acute ingestion, on liver and renal tissues in rats and to what extent this affects the organs’ functions. Animals were divided into five groups: one control group 1 (group C) and four sodium nitrite (NaNO2)–treated group (8 rats per group). The four NaNO2-treated groups include group 2 (N20), group 3 (N40), group 4 (N60), and group 5 (N75). NaNO2 was dissolved in distilled water, and single acute dose was orally given by gavage at 20, 40, 60, and 75 mg/kg body weight, respectively. Our results revealed significant increase of liver enzymes activity—aspartate transaminase (AST), alanine aminotransferase (ALT), and creatinine between different groups with increasing doses of nitrite ingestion. The results of hepatic and renal oxidative stress showed significant increase in the malondialdehyde (MDA) levels and significant decrease in the antioxidant parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as the dose of nitrite increases. Further, the methemoglobin percent showed significant increase with increasing nitrite doses. Abnormal morphological alterations in the liver and kidney tissues were obviously proportional to the administered nitrite doses. The expression of caspase 3 and Bax level showed enhanced induction of immunoexpression, especially in the high doses of nitrites. On the other hand, the maximal immunoexpression level of anti-apoptotic marker Bcl2 was found in lower doses of nitrites, whereas marked decrease of Bcl2 levels was observed in the higher doses. In conclusion, administration of sodium nitrite in a dose-dependent manner is capable of inducing cellular and genetic toxicities and causes disturbance in biochemical analysis, oxidative and anti-oxidative balance, and methemoglobinemia. It also makes histopathological alterations and leads to the activation of apoptosis-related Bax, Bcl2, and caspase 3 genes of liver and kidney tissues in rats.

Nitrite compounds are very important in many industrials that may cause some significant problems, but in more or less cases it has useful effect. Therefore, the present study was carried out to shed the light on the effect of nitrite on streptozotocin (STZ) inducing diabetic rats. In this study, thirty-two male Wister rats were distributed into four groups (n= 8 per group): Group (1) control group; Group (2) normal rats received NaNO2 30 mg/kg body weight; Group (3) diabetic group rats received 45 mg/kg STZ intraperitoneal (IP); Group (4) diabetic rats treated daily with NaNO2 for three months. Serum from each group was collected from rat's blood samples to measure aminotransferase (AST), alanine aminotransferase (ALT), Urea, and Creatinine. A self-assembled nanostructure titania (TiO2) based surface similar to honey cells was synthesized by a simple, fast, low-cost procedure using the 2D electrochemical cell at sequence potential from 5 V to 30 V for 2 h followed by annealed method at 350°C and 750°C for 3 h. A linear sweep voltammetry electrochemical method was used to deposit the Ni-Cu nanoparticles on titania surface providing a highly sensing platform of Ni-Cu/nanotitania array. Both the degree of sensing (46 µA mM−1) for the electrode were calculated through low detection range from 0.00 to 0.35 mM of glucose via cyclic voltammetry and amperometery techniques. By increasing the glucose concentration through the detection range from 0.4 to 2.5 mM the sensitivity increased to 248 µA mM−1. This significant change indicates that the sensitivity of the electrode is suitable for diabetes measurements. We reported for the first electrochemical sensor fabricated from Ni-Cu/nanotitania to detect glucose level in real urine samples and we used this level as a marker for the effect of nitrite present in the drinking water. The results showed that the presence of low concentration of sodium nitrite can enhance the liver and kidney functions in diabetic rats and also lead to the decrease of the glucose concentration in urine. Additionally, Ni-Cu/nanotitania sensor also has stability, profitable good reproducibility and applicability that guarantee its value in the medical applications as in the environmental applications that has been proven previously.

The exponentially increasing use of electromagnetic field (EMF)-emitting devices imposes substantial health burden on modern societies with particular concerns of male infertility. Limited studies have addressed the modulation of this risk by protective agents. We investigated the hazardous effects of rat exposure to EMF (900 MHz, 2 h/day for 8 weeks) on male fertility and evaluated the possible protective effect of the polyamine, spermine, against EMF-induced alterations. Exposure to EMF significantly decreased sperm count, viability and motility, and increased sperm deformities. EMF-exposed rats exhibited significant reductions in serum inhibin B and testosterone along with elevated activin A, follicle-stimulating hormone, luteinizing hormone and estradiol concentrations. Testicular steroidogenic acute regulatory protein (StAR), c-kit mRNA expression and testicular activities of the key androgenic enzymes 3β- and 17β-hydroxysteroid dehydrogenases were significantly attenuated following exposure to EMF. Exposure led to testicular lipid peroxidation, decreased catalase and glutathione peroxidase activities and triggered nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2 and caspase-3 overexpression. EMF-exposed rats showed testicular DNA damage as indicated by elevated comet parameters. Spermine administration (2.5 mg/Kg/day intraperitoneally for 8 weeks) prevented EMF-induced alterations in the sperm and hormone profiles, StAR and c-kit expression and androgenic enzyme activities. Spermine hampered EMF-induced oxidative, inflammatory, apoptotic and DNA perturbations. Histological and histomorphometric analysis of the testes supported all biochemical findings. In conclusion, rat exposure to EMF disrupts sperm and hormone profiles with underlying impairment of steroidogenesis and spermatogenesis. Spermine confers protection against EMF-associated testicular and reproductive aberrations, at least in part, via antioxidant, anti-inflammatory and anti-apoptotic mechanisms.

Dear Editor,We read with interest the report by Murray et al. [1] who investigated the risk factors associated with seizure in single tramadol overdose. Due to their frequency, tramadol-induced sei...

Objectives: Chronic hepatitis C (CHC) is a major health problem in Egypt with about 9.8% of Egyptian population having an active hepatitis C infection. Almost Every step in the Hepatitis C virus (HCV) life cycle is closely related to lipid metabolism. HCV circulate in the body in lipid-rich particle, attach to hepatocytes via lipoprotein receptors. Recent attention focused on HMG CoA Reductase inhibitors (statins) and their potential therapeutic role in hepatitis C. Methods: This retrospective closed cohort study included 60 naive CHC patients. The HCV statins group patients (n = 26) received the combination of Standard of care (Interferon alfa and repavirin) and fluvastatin 80 mg daily; HCV non statins group (n = 43) treated with the SOC treatment only. Both groups receive their treatment over a duration of 48 weeks. Results: On-treatment viral responses as well as the SVR were significantly better in HCV statins group in comparison to HCV non statins group; rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) were (13.3%, 73.3% and 68.3%) in HCV statins group vs. (0%, 58.8% and 52.9%) HCV non statins group with p value 0.00, 0.003 and 0.003 respectively. Multivariate logistic regression model identified statins use as a significant predictor of an SVR. Conclusion: A combination of fluvastatin and SOC significantly improved the SVR in naive CHC Egyptian patients. Further powered randomized control trails are needed to elucidate statins role in HCV treatment.

Introduction: Snakebite is an Egyptian health problem since ancient Egypt. Meanwhile, there is still no controlled geographical and medical studies on locally prevalent snake family intoxication. Aim and Methods: The present study aimed to investigate local snakebites presentations, management, prognosis, and the effect of the polyvalent antivenom, locally produced by the Holding Company for Biological Products and Vaccines (VACSERA) through the year 2015. Results: A total of 87 snakebites caused by venomous and nonvenomous species were recorded. Most cases were middle-aged males. Most cases presented in summer and in the evening time. Two major groups of venomous Egyptian snakes were identified, Viperidae and Elapidae species, based on history, characteristic symptoms, and laboratory findings. Most snakebites (56 cases) were reported to be nonvenomous bites (64.4%). Twenty-one cases (24.1%) of snakebites were reported to be venomous bites by Elapidae snakes and 10 cases (11.5%) were reported to be venomous bites by Viperidae snakes. Antivenom was administered before referral to 37 (42.5%) of cases, and 19 only of them were victims of venomous snakes. Thirty-six (41.3%) patients received antivenom during admission including all cases of the venomous bites and 8.9% of nonvenomous bites' cases. Conclusion: Patients who had moderate or severe symptoms were effectively treated with VACSERA's polyvalent antivenom, with doses related to the severity grading and snake species identification. Additional antivenom doses were repeated on the bases of the clinical condition. Many snakebite victims referred from primary health centers received inadequate or nonnecessary doses of antivenom. No cases of anaphylaxis were recorded. There were no mortalities with current National Center for Clinical and Environmental Toxicology's protocol of treatment.