Novel quinazoline and acetamide derivatives as safe anti-ulcerogenic agent and anti-ulcerative colitis activity

Two novel quinazoline derivatives named as; 3-[(4-hydroxy-3-methoxy-benzylidene)-amino]-2-p-tolyl3H-quinazolin-4-one (5) and 2-p-Tolyl-3-[3,4,5-trimethoxy-benzylidene-amino]-3H-quinazolin-4-one (6) in addition to one acetamide derivative named as 2-(2-Hydroxycarbonylphenylamino)-N-(4- aminosulphonylphenyl) 11 were synthesized, and evaluated for their anti-ulcerogenic & AntiUlcerative colitis activities. All of the three compounds showed curative activity against acetic acid induced ulcer model at a dose of 50 mg/kg, they produced 65%, 85% & 57.74% curative ratio for compounds 5, 6 & 11 respectively. The effect of the tested compounds 5, 6 & 11 at dose 50 mg/kg were significantly (P < 0.01) more effective than dexamesathone (0.1 mg/kg) in reducing all parameters. Compounds showed curative activity of for peptic ulcer (induced by absolute alcohol (at a dose of 50 mg/kg, it produced Curative of control ulcer 56.00%, 61.70% & 87.1% for compounds 5, 6 & 11 respectively at dose 50 mg/kg, while the standard drug (Omeprazole 20 mg/kg) produced 33.3%. In both tests, the activity of our target compounds were higher than the standard drugs used for treatment of peptic ulcer and ulcerative colitis. No side effects were reported on liver and kidney functions upon prolonged oral administration of this compounds

Anti-ulcerogenic and anti-ulcerative colitis (UC) activities of seven amines derivatives

The Novel target compounds (CP-1-7) were synthesized and tested at doses up to 1000mg/kg for their entitled activities. They exerted promising results without any behavioral changes and mortality in mice. Therefore, according to the results obtained in our study, it could be categorized as highly safe agents for treating UC since substances possessing LD50 higher than 50mg/kg are considered nontoxic. They also possessed a potent anti-ulcerogenic activity with different potentials. The most effective compound was CP-4, it produced 97.7% ulcer protection of control followed by CP-3, which produced 90.3% protection, while the standard drug ranitidine (100mg/kg) produced 49.2% protection. Compound CP-1 showed lowest activity among the current series, it produced 55.5% protection. The target compounds were significantly more effective than the standard in reducing ulcer index. The anti-ulcerative colitis activity was tested using acetic acid induced colitis model. The curative effect of the tested compounds at a dose of 50mg/kg oral administration on rats showed a potent anti-ulcerative colitis activity with different potentials. They induced a significant decrease in ulcer score, ulcer area, ulcer index and weight/length of the colon specimens.The percent protection of control colitis ranged from 66.8% for CP-7 to 22.3% for CP-5; however the percent protection for dexamesathone (0.1. mg/kg) was 59.3%. The effect of the tested compounds CP-7 and CP-3 at dose 50. mg/kg were significantly more effective than dexamesathone (0.1. mg/kg) in reducing all parameters.Liver functions were not affected as there is no effect on the activity of both AST and ALT in animals that received the compounds, so the compounds didn't reveal hepatotoxic manifestation. Although, the results on kidney functions showed that, CP-1 slightly elevated blood urea concentration and CP-3 & CP-4 slightly elevated serum creatinine; no apparent nephrotoxic manifestations were recorded

Novel essential amino acid-sulfanilamide hybrid as safe anti-ulcerogenic agent with anti-helicobacter pylori activity

A novel and safe essential amino acid (Leucine) incorporating sulfanilamide was synthesized, and evaluated for its anti-ulcerogenic activity and in vitro anti-Helicobacter pylori activity. The new molecule showed a dose dependent activity against absolute ethanol-induced ulcer in rats, it produced percent protection of control ulcer by 66.7 at dose 100 mg/kg. In addition it showed a potent anti-Helicobacter pylori activity in vitro against 7 clinically isolated strains. The minimum inhibitory concentration (MIC) ranged from 12.5 to 50 μg/ml. The preliminary safety studies and toxicity profile are optimistic and encouraging

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

Prophylactic and curative anti-ulcerogenic activity and the possible mechanisms of action of some desert plants

The present study aimed to evaluate the anti-ulcerogenic activities and the possible mechanisms of action of seven desert plants from different families. Conyza dioscoridis (L.) Desf. (Asteraceae), Euphorbia hirta L. (Euphorpiaceae), Origanum syriacum L., Salvia lanigera L. (Lamiaceae), Sisymbrium irio L., Solanum nigrum Linn. (Solanaceae) and Solenostemma arghel (Del.) Hayne. (Asclepiadaceae), were tested using prophylactic and curative models of absolute ethanol-induced ulcer, at three doses (125, 250 & 500 mg/kg) of each extract. The investigated extracts possessed dose dependent anti-ulcerogenic activities in both models, with LD50 higher than 5 g/kg. The most effective extracts were C. dioscoridis and S. irio with percent protection of control ulcer; 91.1% and 85.4% respectively. The antisecretory activity of both C. dioscoridis and S. irio appears to be mainly related to the suppression of gastrin release. The in vitro potential radical (DPPH) scavenging activities of the investigated extracts were well supported with the reduction in gastric MDA (50.6% and 43.3%) and enhancing the level of reduced GSH (2.84, 2.59 mg/g tissue) for C. dioscoridis and S. irio respectively. In addition, suppression of the inflammatory mediator TNF-α may be one of the possible mechanisms of action. The alcohol extracts of C. dioscoridis and S. irio showed no alteration on liver and kidney functions. Phytochemical screening of the investigated extracts revealed the presence of flavonoids, tannins and sterols which could be related to the activities

Antiulcerogenic activities of the extracts and isolated flavonoids of Euphorbia cuneata Vahl.

The total alcohol extracts of Euphorbia cuneata Vahl.(Euphorbiaceae) were screened for antiulcerogenic activity using an ethanol-induced ulcer model at doses of 125, 250 and 500 mg/kg. The extracts possessed antiulcerogenic activity in a dose-dependent manner. Four flavonoidal compounds were isolated and identified as naringenin, aromadendrin, apigenin and 4'-O-methoxy-luteolin-7-O-rhamnoglucoside, each demonstrating antiulcerogenic activity with curative ratios ranging from 75.78% to 88.23%. In addition, the alcohol extracts and isolated compounds were shown to scavenge the 1,1-diphenyl,2-picrylhydrazyl radical by different ratio, with the most effective being 4'-O-methoxy-luteolin-7-O-rhamnoglucoside (91.14%). The antioxidant activity of the alcohol extracts and the isolated compounds may explain the antiulcerogenic properties. No side effects were observed on either liver or kidney functions

Anti-ulcerative colitis activity of Calotropis procera Linn.

The aim of the present study was to evaluate the anti-ulcerative colitis activity of Calotropis procera. Different extracts of the investigated plant were evaluated; total alcohol extract, polar extract and non-polar extract. All the investigated extracts at doses 200 &400 mg/kg possessed a dose-dependent anti-ulcerative colitis potential when administrated for 5 consecutive days after colitis induction by acetic acid in rats. They reduced different parameters of UC. Only polar extract at both doses (200, 400 mg/kg) was more effective than the standard drug Prednisolone (50 mg/kg), it produced percent protection of control colitis by 63.8% and78.4% respectively, while the standard drug Prednisolone produced 54.9% protection. The anti-ulcerative colitis activity may be attributed to the active principles i.e. flavonoids. Preliminary phytochemical screening showed that the plant contains flavonoids, unsaturated sterols and/or triterpenoides, cardiac glycosides, carbohydrates or glycosides, proteins and/or amino acids, tannins and coumarins. The total alcohol extract was safe up to 4000 mg/kg and there were no side effects reported on liver and kidney functions. Keywords: Calotropis procera, Anti-ulcerative colitis, Anti-inflammatory, Liver function, Kidney function, Phytochemical screenin