Synthesis, identification and anticonvulsant activity of dehydrozingerone

The present study aimed to synthesize and characterize dehydrozingerone as well as to investigate its anticonvulsant activity in experimental animals.  A simple method was used to synthesize dehydrozingerone using vanillin and acetone. The synthesized drug dehydrozingerone was characterized using thin layer chromatography (TLC), high performance liquid chromatography (HPLC), infrared spectroscopy (IR) and physicochemical tests.The synthesized product was  tested for its potential anticonvulsant activity using maximum electroshock (MES) induced seizure models in rats. The synthesized dehydrozingerone showed TLC profile, FT IR spectra and HPLC chromatogram similar to the authentic sample. The physicochemical characters (colour, taste, flavour, solubility and melting point) were also similar to what was found in the literature. All these results indicated that the produced product was dehydrozingerone. A dose dependent anticonvulsant activity was produced by dehydrozingerone. Eighty percent anti-MES activity was presented by 100 mg/kg.  The findings indicated that dehydrozingerone represents a bioactive molecule possessing anticonvulsant activity. In addition, it is an easily synthesized compound from cheap starting materials. In conclusion dehydrozingerone may find its place as antiepileptic agent if further clinical studies will be conducted

Investigation of Anti-nociceptive Activity of Neem (Azadirachta indica) A. Juss on Acetic Acid Induced Writhing in Rats

Background: Plants represent the principal means of therapy in traditional medicine and the plant kingdom has long served as a prolific source of useful drugs. Objective: This study was undertaken to investigate the anti-nociceptive activity of Azadirachta indica A.juss leaf extract in experimental animals.   Methods: Three doses of methanolic extract of Azadirachta indica leaf (100, 200, and 400 mg/kg) were administered intraperitoneally (i.p.) to  investigate their potential antinociceptive activity using acetic acid induced writhing in rats compared to morphine and diclofenac sodium as standard drugs.   Results: The methanolic extract of indica at a dose of 400 mg/kg produced 72.01% protection against writhing induced by acetic acid. This result points to approximately equal protection exhibited by 25mg/kg diclofenac sodium. Co-administration of indica (400 mg/kg) and diclofenac (25 mg/kg) produced 100% protection as diclofenac sodium (50mg/kg) and morphine (2.5, 5 mg/kg). Conclusion and recommendation: On the basis of results obtained, the use of indica leaf extract as antinociceptive seems to be promising. Bioassay guided fractionation of the methanolic extract of indica leaf is recommended for safety and efficacious use. Further work on determination of active ingredient(s) and mechanism of action is also needed

Investigation of anti -nociceptive activity of Zingabeel (Zingiber officinale) on acetic acid induced writhing in rats

This study was carried out to test for antinociceptive effect of the methanolic extract of ginger using acetic acid induced writhing in rats and compared to morphine and diclofenac sodium as standard drugs. The methanolic extract of ginger, showed dose dependent responses whereas 50 and 100mg/kg produced 100%protection against writhing  induced  by  acetic acid (0.6 %  i.p.) .  This protection supersedes the effect of diclofenac sodium (25, 50 and 75 mg/kg). On the other hand morphine (2.5- 10 mg/kg), exhibited 100% protection against writhing induced by acetic acid. Therefore we can conclude and recommend that, ginger is a potential source of new and effective anti-nociceptive agent(s). Bioassay guided fractionation for the methanolic extract of ginger should be investigated for the determination of active ingredient(s), and to elucidate their mechanism of action.  الخلاصة: أجريت هذ الدراسة  لإختبار تأثيرالخلاصة الميثانولية  للزنجبيل كمسكن للألم باستخدام حمض الاستيك الذي يحفز الانقباضات ألبطنيه المسببة للألم ومقارنته بالمورفين و الدايكلوفيناك صوديوم  كأدوية مرجعية. أظهر  المستخلص الميثانولي للزنجبيل إستجابات إعتمادا على  الجرعات حيث إنه في الجرعات  50 و 100مجم/كجم نتجت حماية بنسبة 100% ضد الانقباضات المسببة  بواسطة حمض الأسيتيك (0,6%)˛ حيث يعتبر أفضل تأثيرا من الدايكلوفيناك صوديوم (25، 50، 75مجم/كجم) ومن ناحية أخرى فإن المورفين (2.5 -10 مجم/كج) قد أعطى حماية بنسبة 100% ضد الانقباضات المسببه بواسطة حمض الأسيتيك.  لذا نستنتج   ونوصي بأن الزنجبيل مصدر متوقع  جديد فعال كمسكن للآلام. كما نوصي  بأن تجرى الاختبارات الحيوية الموجهه للتجزئة للزنجبيل لتحديد المادة الفعالة و توضيح آلية عملها.    &nbsp

ANTIOXIDANT AND HEPATOPROTECTIVE EFFECTS OF JUSTICIA SPICIGERA ETHYL ACETATE FRACTION AND CHARACTERIZATION OF ITS ANTHOCYANIN CONTENT

Objective: The antioxidant and hepatoprotective activities of ethyl acetate (EA) fraction of the dried aerial part of Justicia spicigera were evaluated and the characterization of its anthocyanin content was done. Methods: Hepatic fibrosis was induced by carbon tetrachloride (CCl4) in rats. The ethyl acetate fraction was obtained by successive liquid/liquid fractionation of the crude cold ethanolic extract and the pigments were characterized by HPLC technique. The in vitro studies were carried out through evaluation of the EA fraction on the attenuation of 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals. The in vivo biological evaluation was done in CCl4 injured rats through determination of liver function indices, oxidative stress markers and the histopathological picture of the treated liver.Results: The phenolic content in the EA fraction was 42.94 mg/g. Twelve anthocyanins were identified, the major of which are peonidin 3, 5-diglucoside (64.30%), malvidin 3, 5-diglucoside (10.59%) and petunidin 3,5-diglucoside (4.71%). Treatment of CCl4 intoxicated rats with EA fraction recorded improvement in the liver function indices and oxidative stress markers. The histopathological observations confirmed our results.Conclusion: The ethyl acetate fraction of the dried aerial part of Justicia spicigera recorded antioxidant and hepato protective activities.Â

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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

2-(4-Chloro­phenyl)-1,3-di­cyano-6,7-di­hydro-4-imino-9,10-di­methoxy­benzo­[a]­quinolizine–water (2/5)

Crystals of the title compound, C23H17ClN4O2 x 2.5H2O, contain channels filled with highly disordered water molecules. The best structure refinement was obtained by removing the solvent contribution from the intensity data and refining against a solvent-free model. The central six-membered ring of the quinolizine molecule has a slightly distorted screw-boat conformation