In vivo effects of Faizol Ubat Batuk, a herbal product on aminopyrine metabolism in rat hepatocytes

Traditional medicines, in particular herbal products, have been used abundantly over the years in curing several diseases. Pharmacological interactions of herbal products with modern drugs, however, remain to ome extent unknown. Herein, we examined whether co-administration of Faizol Ubat Batuk (FUB), a mixture of aqueous extract of different plants, modifies the metabolism of aminopyrine, a conventional analgesic drug, in rat liver. We used rat hepatocytes outfitted by collagenase perfusion technique. Determination of aminopyrine n-demethylase activity was performed using the Nash colorimetric method, by measuring the amount of formaldehyde produced. Compared to control treatment, FUB significantly increased the hepatic metabolism of aminopyrine in healthy adult male rats. In contrast, the hepatic metabolism of aminopyrine in adult female rats was decreased. Besides, a biphasic effect in n-demethylase activity was observed in young male rats treated with FUB. In a subsequent experiment, FUB did not change the metabolism of aminopyrine in streptozotocin (STZ)-diabetic adult male rats. In conclusion, administration of FUB could affect phase I aminopyrine metabolism in rat heptocytes. In addition, the effects of FUB on hepatic n-demethylase activity were gender and disease dependent.Keywords: drug metabolism; hepatocytes; herbal products; gender; diabetes mellitu

Allergen-specific subcutaneous immunotherapy in allergic asthma: immunologic mechanisms and improvement

Allergic asthma is a disease characterized by persistent allergen-driven airway inflammation, remodeling, and airway hyperresponsiveness. CD4+ T-cells, especially T-helper type 2 cells, play a critical role in orchestrating the disease process through the release of the cytokines IL-4, IL-5, and IL-13. Allergen-specific immunotherapy (SIT) is currently the only treatment with a long-term effect via modifying the natural course of allergy by interfering with the underlying immunological mechanisms. However, although SIT is effective in allergic rhinitis and insect venom allergy, in allergic asthma it seldom results in complete alleviation of the symptoms. Improvement of SIT is needed to enhance its efficacy in asthmatic patients. Herein, the immunoregulatory mechanisms underlying the beneficial effects of SIT are discussed with the ultimate aim to improve its treatment efficacy.Keywords: allergic asthma; immunotherapy; dendritic cell; regulatory T cells; Th2 lymphocytes; hyperresponsiveness; eosinophilia; IgE; IL-1

Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli

Background: The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits.Aim: The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes. Methods: A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including 179 females (89.05%) and 22 males (10.95%), were recruited from different academic levels. Data were collected using a structured questionnaire and included a number of life-style variables. Epworth Sleepiness Scale (ESS) was used for the assessment of daytime sleepiness. Results: This study showed that the total sleep time (TST) on a weeknight was 6.40 h and 67 students reported napping during daytime. The TST plus naps totalled 7.39 h. Out of eight possible dozing situations, we found that the mean score for ESS was 8.78. In addition, 79 students showed an ESS score of 10. Furthermore, our results showed that the majority of students (92%) reported poor sleep satisfaction with quality and duration of sleep hours. Thinking about difficulty of study but not increasing education programs or tea/coffee consumption is associated with sleep difficulties reported. Moreover, 77.6% of students reported an irregular sleepwake schedule. Conclusion: These findings indicate that students experienced excessive daytime sleepiness. The TST of pharmaceutical students in Libya, as in other developing countries, is less than those reported by Western students. Students experienced various environmental demands during their college years and, their quality of sleep was negatively affected.Keywords: college students; sleep habits; sleep disorders; Epworth Sleepiness Scal

Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil inmice

Background: Clove oil of Eugenia caryophyllata (Myrtaceae) is a light yellowish fluid obtained from dried flower buds. Clove oil is used traditionally to relieve toothache.Aim: The aim of the present work was to study the anti-inflammatory, antinociceptive and antipyretic potential of clove oil in mice.Methods: Analgesic activity was examined using acetic-acid-induced abdominal constrictions and the hot plate test. Carrageenan-induced paw edema and brewer’s-yeast-induced pyrexia were used to investigate the anti-inflammatory activity and the antipyretic effects, respectively. The oil was administered intraperitoneally (i.p.) at a dose of 33 mg/kg body weight and the effects were compared with reference drugs.Results: In the antinociceptive test, mice treated with clove oil exhibited significantly decreased acetic-acidinducedwrithing movements by a maximum of 87.7% (p<0.01) compared with a decrease of 77.7% (p<0.01) in response to aspirin injection (100 mg/kg, intraperitoneal, i.p.). Similarly, in the hot plate test, clove oil significantly increased the reaction latency to pain after 60 min by 82.3% (p<0.05) compared with morphine value of 91.7% (p<0.01). In addition, clove oil and indomethacin produced anti-inflammatory effects, as demonstrated by respectively 50.6% (p<0.05) and 70.4% (p<0.01) inhibition of mouse paw edema induced by carrageenan. Furthermore, clove oil significantly attenuated the hyperthermia induced by yeast at ΔT-max by 2.7oC (p<0.001), and time of peak effects was 30-180 min compared with a paracetamol value ΔT-max of 3.2oC (p<0.001). The estimated i.p. LD50 of clove oil was 161.9 mg/kg. Phytochemical screening of the oil showed the presence of eugenol.Conclusion: The present findings demonstrate the potential pharmacological properties of clove oil and provide further a support for its reported use in folk medicine.Keywords: Eugenia caryophyllata; clove oil; eugenol; antinociceptive; anti-inflammatory; antipyretic; mic

Antinociceptive activity of Mentha piperita leaf aqueous extract in mice

Mentha piperita L. (Labiatae) is an herbaceous plant, used in folk medicine for the treatment of several medical disorders.In the present study, the aqueous extract of Mentha piperita leaf, at the i.p doses 200 and 400 mg/kg, showed significant analgesic effects against both acetic acid-induced writhing and hot plate-induced thermal stimulation in mice, with protection values of 51.79% and 20.21% respectively. On the contrary, the Mentha piperita leaf aqueous extract did not exhibit anti-inflammatory activity against carrageenan induced paw oedema.These findings indicate that Mentha piperita has a potential analgesic effect that may possibly have mediated centrally and peripherally, as well as providing a pharmacological evidence for its traditional use as a pain reliever

Prevention of Birch Pollen-Related Food Allergy by Mucosal Treatment with Multi-Allergen-Chimers in Mice

Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy

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

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

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 middle-income 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 low-income 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 low-income, 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