Modulation of L-arginine-induced acute pancreatitis by meloxicam and/or L-carnitine in rats

Background: Acute pancreatitis (AP) is an inflammatory disease, where oxidative stress, subsequently inflammatory mediators activation play a pivotal role. Currently, no definite treatment exists and therapy is mainly supportive that directed to inhibit local pancreatic injury and systemic inflammatory complications. This study is presented to explore whether anti-inflammatory and/or antioxidant drug could ameliorate L-arginine-induced AP.Methods: Rats were sub-grouped randomly into five groups. Control group, AP was provoked by a single intraperitoneal injection of L-arginine (250 mg/100g), rat treated with meloxicam (4 mg/kg, IP), animals treated with L-carnitine (500 mg/kg, IP), and rats were treated with both meloxicam and L-carnitine. All treatments were once daily for 7 consecutive days and started 1 hr later after L-arginine administration. Serum and tissues samples were prepared for biochemical analysis. Histopathological examination for the other pancreatic tissues was done.Results: L-arginine significantly elevated serum activity of amylase and lipase enzymes, while notably reduced serum calcium level. Moreover, L-arginine markedly increased the pancreatic tissues content of tumor necrosis factor-α, malondialdehyde, and nitric oxide. In addition, L-arginine significantly increased pancreatic activity of myeloperoxidase, while markedly depleted glutathione level. Treatment with either meloxicam or L-carnitine significantly attenuated L-arginine-induced biochemical changes. On the other hand, co-administration of both meloxicam and carnitine has an ameliorative effect greater than each drug alone.Conclusion: Treatment with both meloxicam and L-carnitine is a more effective than each of them alone which is attributed to augmentation their antioxidant, anti‑inflammatory effects

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

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

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

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Acetovanillone augmented the cardioprotective effect of carvedilol against cadmium-induced heart injury via suppression of oxidative stress and inflammation signaling pathways

Abstract Cardiac toxicity is a public health issue that can be caused by both environmental and occupational exposures. The current study aimed to investigate the effectiveness of carvedilol (CV), Acetovanillone (ACET), and their combination for ameliorating cadmium (Cd)-induced oxidative stress, inflammation, and necroptosis. Rats were assigned to; the normal group, Cd group (2 mg/kg; i.p., single dose), and the other three groups received orally CV (10 mg/kg), ACET (25 mg/kg), and CV plus ACET, respectively and a single dose of Cd. Oral administration of CV, ACET, and their combination significantly dampens cardiac oxidative injury by increasing antioxidants GSH and SOD levels, while it decreases MDA and NADPH oxidase levels mediated by decreasing cardiac abundance of Nrf2, HO-1, and SIRT1 and downregulating KEAP-1 and FOXO-3 levels. Also, they significantly attenuated inflammatory response as indicated by reducing MPO and NOx as well as proinflammatory cytokines TNF-α and IL-6 mediated by downregulating TLR4, iNOS, and NF-κB proteins expression as well as IκB upregulation. Moreover, they potently counteracted cardiac necroptosis by downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins expression. Of note, the combination of CV and ACET have marked protection that exceeded each drug alone. Conclusively, CV ad ACET potently mitigated Cd-induced cardiac intoxication by regulating NADPH oxidase, KEAP-1/Nrf2/HO-1, SIRT1/FOXO-3, TLR4/NF-κB/iNOS, and RIPK1/RIPK3/MLKL signals

Nutritional impact of inclusion of garlic (Allium sativum) and/or onion (Allium cepa L.) powder in laying hens’ diets on their performance, egg quality, and some blood constituents

Abstract Background Many studies mentioned that using medicinal herbs and plants as feed additives to ruminants seems to be a recent trend depending on the availability and their cost but using them with monogastric animals and birds, as pharmaceutical tool, is available. As an example, the importance of garlic or onion in recent years, thanks to a wide range of useful properties, has been increasingly used as an additive in nutrition and protection of farm animals. Their action was manifested in a reduced expanding range of pathogenic microorganisms in the digestive tract, which resulted in the rapid growth of poultry, efficient digestion, and increased immunity and health of poultry. Methods One hundred and eight 30-week-old laying hens were randomly divided into six dietary treatment groups {G1 control, G2 contained 0.5% garlic powder (GP), G3 contained 1% GP, G4 contained 1% onion powder (OP), G5 contained 1% OP + 0.5% GP, and G6 contained 1% OP + 1% GP}. Each group included 18 hens in six replicates (3 birds/each). So, this work carried out to investigate the impact of incorporating garlic powder (GP) and/or onion powder (OP) in laying hens’ diets on their performance, egg quality, and some blood constituents. Results Incorporating GP, OP, and the mixture of them in laying hen diets had no significant effect on the average egg weight and consumption/hen/day throughout the three stages of egg collection, but had a significant improvement in the number of eggs/hen, percentage of egg production, egg mass/hen, and feed conversion. Inclusion of GP, OP, or the mixture of them in laying hen diets had no significant effect on the shape index, Haugh unit, albumin, and shell percentages; also, an insignificant increase for shell thickness was observed, but egg weight increases (P < 0.05). Incorporation of GP, OP, and the mixture of them significantly decreased (P < 0.05) total cholesterol concentration. Also, an inclusion of 0.5% GP, 1% GP, and 1% OP + 1% GP decreased (P < 0.05) high-density lipoprotein. Inclusion of only 1% OP + 1% GP (G6) decreased (P < 0.05) glutamic oxaloacetic transaminase; meanwhile, supplementation of 1% OP, 1% OP + 0.5% GP, or 1% OP + 1% GP increased (P < 0.05) creatinine. Conclusion From the results obtained and under conditions suitable for this study, it can be mentioned that the incorporation of garlic or onion powder or the mixture of them can be safely used with improvement in the general health of hens, egg weight, and feed conversion and decrease in the blood cholesterol

Sistema sociotécnico dos resíduos sólidos do Estado do Espírito Santo : estrutura para um plano municipal de gestão integrada de resíduos sólidos

Esta Tese aborda a gestão de resíduos sólidos urbanos (RSU) nos municípios do estado do Espírito Santo. Foi feito levantamento a partir de dados mais recentes do Instituto Brasileiro de Geografia e Estatística (IBGE), do Ministério do Meio Ambiente (MMA), do MCIDADES através do Sistema Nacional de Informações sobre Saneamento (SNIS) e SNIS-RS, e o próprio sistema on-line do SNIS, da Associação Brasileira de Empresas de Limpeza Pública e Resíduos Especiais (ABRELPE), e documentos oficiais de domínio público, principalmente os Termos de Compromisso Ambiental (TCA), cujas assinaturas são necessárias para que os municípios tenham acesso a verbas federais previstas na Lei que rege a Política Nacional de Resíduos Sólidos (PNRS). A pesquisa resultou no mapeamento do sistema sociotécnico de gestão de RSU (atores envolvidos, processos de trabalho e equipamentos utilizados) do Espírito Santo, na identificação de práticas no estado e em outras regiões no Brasil e no exterior, que permitiram o delineamento de um Plano Geral de Gestão Municipal de RSU, contemplando itens destacados na PNRS: promoção da redução de resíduos, coleta seletiva, reaproveitamento, reciclagem/compostagem, incentivo e apoio às cooperativas de catadores e recicladores, a extinção dos lixões e melhor destinação final de resíduos, responsabilidade compartilhada, logística reversa, educação ambiental, pesquisa científica e tecnológica, monitoramento e fiscalização das ações. A estrutura do Plano, que foi previsto para ser informatizado, deve servir de guia e apoio aos municípios no que tange ao entendimento do sistema e estabelecimento de metas, pode dar mais transparência ao uso dos recursos e, portanto, maior controle. Quando informatizado, além de facilitar sua otimização e implementação, e de ser uma ferramenta de controle, pode servir também para disseminação de informação e conhecimento, e portanto, de capacitação de pessoal, de integração entre os atores e os subsistemas da gestão integrada de RSU em um município.This thesis addresses the management of municipal solid waste (MSW) in the cities of Espírito Santo state. A survey was carried out using the latest data from the Brazilian Institute of Geography and Statistics (IBGE), the Ministry of Environment (MMA), MCIDADES through the National Information System on Sanitation (SNIS) and SNIS-RS, and the National Association of Public Cleaning and Special Waste Companies (ABRELPE), and official documents in the public domain, especially the Environmental Commitment Terms (TCA), whose signatures are necessary for cities to have access to government funds provided for in the law that governs the National Solid Waste Policy (PNRS). This research resulted in the mapping of the socio-technical system of MSW management (involved actors, work processes and equipment used) of Espírito Santo, in the identification of practices in the State and in other regions in Brazil and abroad, which allowed the design of a Plan General of Municipal Management of MSW, including items highlighted in the PNRS: promotion of waste reduction, selective collection, reuse, recycling / composting, incentive and support to cooperatives of waste pickers and recyclers, dump extinction and final disposal of waste, responsibility shared logistics, reverse logistics, environmental education, scientific and technological research, monitoring and enforcement of actions. The structure of the Plan, which was intended to be computerized, should serve as a guide and support to municipalities in understanding the system and setting goals, can give more transparency to the use of resources and, therefore, greater control. When computerized, in addition to facilitating its optimization and implementation, and being a control tool, it can also serve to disseminate information and knowledge, and therefore, to train staff, integrate stakeholders and the various integrated management system subsystems. RSU in the municipality

Phytochemical Characterization of Pterocephalus frutescens with In-Silico Evaluation as Chemotherapeutic Medicine and Oral Pharmacokinetics Prediction Study

Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in the field of in-silico modelling and computer-based drug design by orienting and scoring ligands in the active binding site of a target protein. The phytochemical investigation of the Pterocephalus frutescens extract in n-butanol resulted in the isolation and structure elucidation of three iridoids and four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) and Orientin (7), respectively. Molecular docking studies were used to compare the binding energies of the isolated phytochemicals at four biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty acid synthase, and topoisomerase II-DNA complex. The docking study concluded that the isolated compounds have promising cytotoxic activities, in particular, Luteolin-7-O-glucoside (5) and Orientin (7) which exhibited high binding affinities among the isolated compounds at the active sites of the target enzymes; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), respectively, surpassing the corresponding binding scores of the co-crystallized ligands and the reference drugs at these target enzymes. Additionally, among the isolated compounds, Luteolin-7-O-glucoside (5) showed the most outstanding binding affinities at the active sites of the target enzymes; Fatty acid synthase, and Topisomerase II-DNA complex with binding scores of −6.82, and −7.99 Kcal/mol, respectively. Finally, the SwissADME online web tool predicted that most of these compounds possessed acceptable oral bioavailability and drug likeness characteristics