Two Chromatographic Methods for the Determination of Some Antimigraine Drugs

Two stability indicating chromatographic methods were proposed for the determination of almotriptan, eletriptan, and rizatriptan, in presence of their acid degradation products. The first method is a quantitative densitometric thin layer chromatography. The developing systems were; acetonitrile: methanol: dichloromethane: ammonia (10:6:3:1 v/v), ethyl acetate: methanol: ammonia (15:4:1 v/v), and methanol: acetonitrile: ammonia (9:4:1 v/v) for almotriptan, eletriptan and rizatriptan respectively. The TLC plates were scanned at 235 nm. Linear relationships were obtained over concentration ranges (5–50 μg/spot) for almotriptan and rizatriptan, and (5–60 μg/spot) for eletriptan. The second method based on the separation and determination of the studied drugs, using RP-HPLC technique. The separation was achieved on C18 Hypersil column, elution was carried out using phosphate buffer pH 3: methanol: acetonitrile (2: 1:1 v/v) at flow rate 2 mL/min and UV detection at 235 nm. Linear relationships were obtained over concentration ranges (10–200 μg/mL) for almotriptan and eletriptan, and (10–180 μg/mL) for rizatriptan. The chromatographic methods were successfully applied for the determination of each of the studied drugs in pure form, tablet form, and in laboratory prepared mixtures with their acid degradation products

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Non-thermal continuous and modulated electromagnetic radiation fields effects on sleep EEG of rats

In the present study, the alteration in the sleep EEG in rats due to chronic exposure to low-level non-thermal electromagnetic radiation was investigated. Two types of radiation fields were used; 900 MHz unmodulated wave and 900 MHz modulated at 8 and 16 Hz waves. Animals has exposed to radiation fields for 1 month (1 h/day). EEG power spectral analyses of exposed and control animals during slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) revealed that the REM sleep is more susceptible to modulated radiofrequency radiation fields (RFR) than the SWS. The latency of REM sleep increased due to radiation exposure indicating a change in the ultradian rhythm of normal sleep cycles. The cumulative and irreversible effect of radiation exposure was proposed and the interaction of the extremely low frequency radiation with the similar EEG frequencies was suggested

Advantages of Cubosomal Formulation for Gatifloxacin Delivery in the Treatment of Bacterial Keratitis: In Vitro and In Vivo Approach Using Clinical Isolate of Methicillin-Resistant Staphylococcus aureus

The objective of this study was to enhance the corneal permeation of gatifloxacin (GTX) using cubosomal nanoparticle as a delivery system. Cubosomal nanoparticle loaded with GTX was prepared and subjected for in vitro and in vivo investigations. The prepared GTX-loaded cubosomal particles exhibited nanoparticle size of 197.46 &plusmn; 9.40 nm and entrapment efficiency of 52.8% &plusmn; 2.93. The results of ex vivo corneal permeation of GTX-loaded cubosomal dispersion show approximately 1.3-fold increase compared to GTX aqueous dispersion. The incorporation of GTX into cubosomal particles resulted in a fourfold reduction in the minimum inhibitory concentration (MIC) value for the GTX cubosomal particles relative to GTX aqueous dispersion. Furthermore, the enhanced corneal penetration of GTX-loaded cubosomal dispersion compared was evident by a significant decrease in the area % of corneal opacity in MRSA infected rats. Moreover, these results were confirmed by photomicrographs of histological structures of corneal tissues from rats treated with GTX-cubosomal dispersion which did not present any change compared to that of the normal rat corneas. In conclusion, treatment of ocular bacterial infections and reduction in the probability of development of new resistant strains of MRSA could be accomplished with GTX-loaded cubosomal nanoparticles

Enhancement of punching shear strength of flat slabs using shear-band reinforcement

Flat-slab system is widely used nowadays. Major and critical problem of this system is its sudden brittle failure is called punching shear failure. To overcome the punching failure problem, there are many ways to increase the punching shear strength of concrete slabs, increasing slab thickness in the area adjacent to the column, increasing column thickness which is against the architectural desire, and finally providing slab with shear reinforcement. Shear reinforcement is more advanced from both the structural and economical point of view.An experimental program includes seven full scale square flat slab interior column specimens tested under gravity loads. All slabs have same dimensions of 1700 mm × 1700 mm with thickness 160 mm and reinforcement ratio of 1.2%. Column was square of 200 mm length and 250 mm height. Elongated steel strips of 25 mm width and 1.5 mm thickness undulated into the slab in different ways to investigate punching shear resistance.The program is divided into five groups. First group investigates the effect of installing the shear-band reinforcement (hanged up on top mesh, knit the top and bottom mesh together). The second group investigates the effect of inclination of shear reinforcement (shear band with vertical leg, with bended leg 45°). The third group investigates the effect of concentrating the shear reinforcement by increasing the quantity around the column. The fourth group investigates effect of radial distribution of shear-band system around the column. Finally, the fifth group investigates the effect of box distribution of shear-band system around the column. Keywords: Flat slab, Shear band, Punching shear, Failure loa

Nigella sativa as an anti-inflammatory and promising remyelinating agent in the cortex and hippocampus of experimental autoimmune encephalomyelitis-induced rats

Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of multiple sclerosis. This study aimed to investigate the protective and therapeutic effects of Nigella sativa (N. sativa) seeds (2.8 g/kg body weight) in EAE-induced rats. EAE-induced animals were divided into: (1) EAE-induced animals (“EAE” group). (2) “N. sativa + EAE” group received a daily oral administration of N. sativa 2 weeks prior to EAE induction until the end of the experiment. (3) “EAE + N. sativa” group received a daily oral administration of N. sativa after the appearance of the first clinical signs until the end of the experiment. All animals were sacrificed at the 28th day post EAE-induction. Disease pathogenesis was monitored using a daily clinical scoring, body weight, open field test, histopathological and ultrastructural examination and determination of some oxidative stress parameters in the cortex and hippocampus. N. sativa ameliorated the clinical signs and suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the hippocampus. However, protection of rats with N. sativa administered 2 weeks prior to EAE induction and its continuation until the end of the experiment resulted in a significant increase in the cortical lipid peroxide level with reference to control and “EAE” rats. In conclusion, N. sativa seeds could be used as a protective agent or an adjunct treatment for EAE even when the treatment started after the appearance of the first clinical signs. However, the dose and duration of N. sativa must be taken into consideration to avoid its probable pro-oxidant effect

Evaluation of the neuroprotective effect of taurine and green tea extract against oxidative stress induced by pilocarpine during status epilepticus

Status epilepticus (SE) has functional and structural consequences resulting in brain damage. The present study aims to investigate the role of taurine and green tea extract in the neuroprotection against oxidative stress and changes in acetylcholinesterase (AChE) and Na+,K+-ATPase activities during SE induced by pilocarpine in the hippocampus of adult male rats. Animals received an oral administration of either taurine (100 mg/kg) or green tea extract containing 100 mg/kg epigallocatechin gallate for 3 days before the induction of SE with pilocarpine (380 mg/kg, i.p.) and were sacrificed 1 h after pilocarpine injection. Data indicated that a state of oxidative stress has evolved during SE as evident from the significant increase in lipid peroxidation level and significant decrease in reduced glutathione (GSH) level. Significant decreases in AChE and Na+,K+-ATPase activities were also recorded. Pretreatment of rats with taurine exaggerated the increase in lipid peroxidation and failed to prevent the decrease in Na+,K+-ATPase activity resulting from pilocarpine. However, taurine pretreatment prevented the reduced activity of hippocampal AChE induced by pilocarpine during SE. Pretreatment of rats with green tea extract prevented the increase in lipid peroxidation occurring during SE. However, it failed to inhibit the decrease in Na+,K+-ATPase activity. In conclusion, taurine pretreatment failed to reduce the oxidative stress induced during SE. In contrast, pretreatment of rats with green tea extract ameliorated the oxidative stress induced by pilocarpine and this may assist in reducing the insults of hyperexcitability and excitotoxicity that occur during SE and thereby reduce neuronal damage

Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies

The Ebola virus (EBOV) outbreak was recorded as the largest in history and caused many fatalities. As seen in previous studies, drug repurposing and database filtration were the two major pathways to searching for potent compounds against EBOV. In this study, a deep learning (DL) approach via the LigDream tool was employed to obtain novel and effective anti-EBOV inhibitors. Based on the galidesivir (BCX4430) chemical structure, 100 compounds were collected and inspected using various in silico approaches. Results from the molecular docking study indicated that mol1_069 and mol1_092 were the best two potent compounds with a docking score of −7.1 kcal mol−1 and −7.0 kcal mol−1, respectively. Molecular dynamics simulations, in addition to binding energy calculations, were conducted over 100 ns. Both compounds exhibited lower binding energies than BCX4430. Furthermore, compared with BCX4430 (%Absorption = 60.6%), mol1_069 and mol1_092 scored higher values of % Absorption equal to 68.1% and 63.7%, respectively. The current data point to the importance of using DL in the drug design process instead of conventional methods such as drug repurposing or database filtration. In conclusion, mol1_069 and mol1_092 are promising anti-EBOV drug candidates that require further in vitro and in vivo investigations

Ameliorative Impacts of Wheat Germ Oil against Ethanol-Induced Hepatic and Renal Dysfunction in Rats: Involvement of Anti-Inflammatory, Anti-Apoptotic, and Antioxidant Signaling Pathways

Wheat germ oil (WGO) is a well-known product with anti-inflammatory and antioxidant properties. The current study aimed to investigate the impacts of WGO against ethanol-induced liver and kidney dysfunction at the serum, anti-inflammatory, antioxidants and anti-apoptotic signaling pathways. Rats received saline orally as a negative control or WGO in a dose of 1.5 mL/kg (1400 mg/kg body weight orally) for 15 days. The affected group received ethanol 50% v/v 10 mL/kg (5 g/kg) body weight orally once a day for consecutive 15 days to induce hepatorenal injuries in ethanolic non-treated group. The protective group received WGO daily 1 h before ethanol administration. Serum (1.5 mL) from blood was extracted and examined for the changes in biochemical assessments in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, serum γ-glutamyl transpeptidase (GGT), total protein, serum albumin, butyrylcholinesterase (BChE), total cholesterol (TC), total triglyceride (TG), urea, creatinine, uric acid, potassium (K+), Beta-2 microglobulin (β2M), malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and aspartate aminotransferase (AST). Kidney and liver homogenate was used to measure MDA, GSH and catalase activities. Quantitative real time PCR (qRT-PCR) was used to express Nrf2 and HO-1 in liver, and NF-kB and kidney injury molecule (KIM-1) in kidneys, which are correlated with oxidative stress and inflammation. Capase-3 and Bcl2 genes were examined using immunohistochemical analysis in the kidney and liver. Ethanol administration induced significant alteration in examined liver and kidney markers (AST, ALT, GGT, ALP, total proteins, urea, creatinine and uric acid). Moreover, alcohol administration decreased antioxidant activities at serum and hepatorenal tissues (GSH, catalase and SOD), while MDA was increased as a tissue degradation marker. Inflammatory cytokines, together with genes of oxidative stress markers (Nrf2 and HO-1), were all affected. At cellular levels, apoptotic marker caspase-3 was upregulated, while antiapoptotic marker B-cell lymphoma 2 (Bcl2), was down regulated using immunohistochemical analysis. Of interest, pretreatment with WGO improved the side effects induced by ethanol on hepatic, renal biomarkers and reversed its impact on serum and tissue antioxidant parameters. Nrf2/HO-1 were upregulated, while NFk-B and KIM-1 were downregulated using real time PCR. Immune reactivities of caspase-3 and Bcl2 genes were restored in the protective group. In conclusion, WGO ameliorated ethanol-induced hepatic and renal dysfunction at the biochemical, molecular and cellular levels by regulating some mechanisms that controls oxidative stress, apoptosis, inflammation and anti-apoptotic pathways