Study of Treg FOXP3 in childhood bronchial asthma in relation to corticosteroid therapy

Background: T cells are considered the main cells responsible for production of suppressive cytokines, and play a key role in balancing the immune responses to maintain the peripheral tolerance against allergens. Objective: The present study investigates T regulatory (Treg) forkheadwinged helix protein 3 FOXP3 expression in childhood asthma and its relation to corticosteroid therapy. Methods: In this case control study, Treg FOXP3 was measured in blood of 60 children using real time polymerase chain reaction (RT-PCR) technique. Two asthmatic groups were included, one on corticosteroid therapy (20 patients) and the other not on corticosteroid treatment (20 patients). They were compared to 20 healthy children as controls. Results: FOXP3 concentration was significantly elevated in asthmatic patients (90 ± 77.4) compared to healthy children (12.844 ± 10.6) (p= 0.000). FOXP3 was significantly more elevated in asthmatics on corticosteroids (161.158 ± 63.9) than steroid naive asthmatics (36.038 ± 23.4) (p=0.000). Levels of Treg FOXP3 in asthmatics with inhaled corticosteroids (mean 151.16 ± 53.79) were almost similar to FOXP3 in asthmatics with systemic corticosteroids (161.49±72.5) (p>0.05). FOXP3 levels did not differ with smoking, asthma severity or disease control and did not correlate with age, FEV1, blood lymphocytes percentage or eosinophils percentage. Conclusion: Asthmatics have increased expression of FOXP3, and corticosteroid therapy –whether oral or inhaled - enhances FOXP3 expression.Keywords: FOXP3, Treg, Corticosteroids, Bronchial asthma, Transcription factors, CytokinesEgypt J Pediatr Allergy Immunol 2012;10(1):39-43

Phytochemical investigation of Rhus tripartita and its activity against cyclooxygenases and acetylcholinesterase

Purpose: To investigate the inhibitory activity of crude methanol extract, fractions and two pure compounds from Rhus tripartita stem cyclooxygenases (COX-1 and COX-2) and acetylcholinesterase (AChE); also, to evaluate their antioxidant properties in in-vitro assays.Methods: R. tripartita extract and fractions were examined as inhibitors of COX-1 and COX-2 and AChE. Their antioxidant properties were also evaluated using various antioxidant tests, including free radical scavenging, nitric oxide, and total antioxidant capacity.Results: Ethyl acetate fraction (RT2), aqueous fraction (RT4), subfraction RT2-II, and subfraction RT2-III had a potent inhibitory effect on AChE with low IC50 values. At the same time, a subfraction (RT2-III) was an effective COX-2 inhibitor (94.5 % at 10 μg/mL) followed by ethyl acetate fraction (RT2; 79.39 %), aqueous fraction (RT4; 70 %), total extract (RT; 66.18 %), subfraction RT2-III (64.08 %), compound 5 (epicatechin; 61.25 %), compound 2 (taxifolin; 55.63 %), subfraction RT2-II (46.85 %), and butanol fraction (RT3; 40.80%). RT2, RT4, RT2-II, RT2-III, and compound 2 each showed 100 % inhibition at 20 μg/mL.Conclusion: The ethyl acetate fraction (RT2), aqueous fraction (RT4) and subfractions RT2-II and RT2- III are effective natural inhibitors of AChE. Subfraction RT2-III is the best COX-2 inhibitor, followed by ethyl acetate fraction RT2 and aqueous fraction (RT4). These bioactive materials can be considered natural COX-2 and AChE inhibitorsKeywords: Cyclooxygenase, Anti-nflammatory, Acetylcholinesterase, Anacardiaceous, Taxifolin, Epicatechi

EFFECT OF ACIDIC MARINATION ON THE QUALITY CHARACTERISTICS OF SPENT HEN KOBEBA DURING FROZEN STORAGE

Marinated spent hen meats were used in the preparation of kobeba. The chemical, physicochemical, microbiological and sensory properties of kobeba were evaluated during storage at -18˚C for 5 months. Kobeba treated with lime juice had higher crude protein (14.03%), crude fat (7.78%), total ash (3.18%), carbohydrates (8.69%), cooking loss (5.62%), water holding capacity (3.41 cm2/0.3g) and plasticity (2.30 cm2/0.3g) and lower moisture (66.41%) and pH (5.96) than kobeba treated with propionic acid and acetic acid. Lime juice, acetic acid and propionic acid marination reduced total volatile nitrogen values by 25.82, 20.53 and 11.20% and thiobarbituric acid values by 33.82, 25.37 and 18.38%, respectively. Lime juice followed by acetic acid was more effective in reducing total bacterial, psychrophilic bacteria and yeast and mold counts than propionic acid. Kobeba marinated with lime juice had higher rating scores (7.68-7.98) for all sensory properties than kobeba marinated with propionic acid and acetic acid. Total volatile nitrogen, thiobarbituric acid, pH, water holding capacity and cooking loss of kobeba were increased as storage period increased. However, plasticity had an opposite trend. Water and fat retention of kobeba were not affected by storage period. At the end of storage period, kobeba had rating scores described as like slightly (6.19-6.45) for all sensory properties

Biochemical and histological evidences for the antitumor potential of Teucrium Oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma

Background: Teucrium oliverianum and Rhazya stricta are medicinal plants used in traditional and herbal medicine for the treatment of diabetes, liver diseases and inflammatory conditions. The present study was planned to investigate the antitumor efficacy of Teucrium oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma (HCC) in rats.Materials and Methods: Forty adult male rats weighing 170-200 g were divided into four groups; each group was comprised of ten rats: (1): Normal healthy animals served as negative control group, (2):  Hepatocellular carcinoma (HCC) group in which the rats were orally administered Nnitrosodiethylamine (dissolved in 0.9% normal saline), in a dose of 20 mg/kg b.wt. five times a week for six weeks, (3): HCC group treated with Teucrium oliverianum extract in a dose of 600 mg/kg b.wt for two months and (4): HCC group treated with Rhazya stricta extract in a dose of 750 mg/kg b.wt for two months. Serum alanine  aminotransferase (ALT), asparatate aminotransferase (AST), alkaline phosphatase (ALP) and  gammaglutamyl transferase (γ-GT) activities were estimated. Serum  carcinoembyronic antigen (CEA), alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), glypican-3 (GPC-3), golgi protein 73 (Gp-73) and vascular endothelial growth factor (VEGF) levels were determined. Histopathological examination of liver tissue sections was also carried out.Results: The HCC group showed significant elevation in serum AST, ALT, ALP and γ-GT activities as well  as CEA, AFP, AFU, Gpc-3, Gp 73 and VEGF levels versus the negative control group. Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis.Conclusion: Treatment of HCC groups with Teucrium oliverianum or Rhazya stricta extract experienced significant improvement in the measured biochemical parameters as well as in the structural  organization of the liver. In conclusion, the current study provided experimental evidences for the antitumor efficacy of Teucrium oliverianum and Rhazya stricta against hepatocellular carcinoma. Such effect could be attributed to hepatoprotective properties, antiproliferative activity and antiangiogenic potential.Keywords: Hepatocellular carcinoma, Teucrium oliverianum, Rhazya stricta, rat

BIOCHEMICAL AND HISTOLOGICAL EVIDENCES FOR THE ANTITUMOR POTENTIAL OF TEUCRIUM OLIVERIANUM AND RHAZYA STRICTA IN CHEMICALLY-INDUCED HEPATOCELLULAR CARCINOMA

Background: Teucrium oliverianum and Rhazya stricta are medicinal plants used in traditional and herbal medicine for the treatment of diabetes, liver diseases and inflammatory conditions. The present study was planned to investigate the antitumor efficacy of Teucrium oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma (HCC) in rats. Materials and Methods: Forty adult male rats weighing 170-200 g were divided into four groups; each group was comprised of ten rats: (1): Normal healthy animals served as negative control group, (2): Hepatocellular carcinoma (HCC) group in which the rats were orally administered Nnitrosodiethylamine (dissolved in 0.9% normal saline), in a dose of 20 mg/kg b.wt. five times a week for six weeks, (3): HCC group treated with Teucrium oliverianum extract in a dose of 600 mg/kg b.wt for two months and (4): HCC group treated with Rhazya stricta extract in a dose of 750 mg/kg b.wt for two months. Serum alanine aminotransferase (ALT), asparatate aminotransferase (AST), alkaline phosphatase (ALP) and gammaglutamyl transferase (γ-GT) activities were estimated. Serum carcinoembyronic antigen (CEA), alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), glypican-3 (GPC-3), golgi protein 73 (Gp-73) and vascular endothelial growth factor (VEGF) levels were determined. Histopathological examination of liver tissue sections was also carried out. Results: The HCC group showed significant elevation in serum AST, ALT, ALP and γ-GT activities as well as CEA, AFP, AFU, Gpc-3, Gp 73 and VEGF levels versus the negative control group. Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis. Conclusion: Treatment of HCC groups with Teucrium oliverianum or Rhazya stricta extract experienced significant improvement in the measured biochemical parameters as well as in the structural organization of the liver. In conclusion, the current study provided experimental evidences for the antitumor efficacy of Teucrium oliverianum and Rhazya stricta against hepatocellular carcinoma. Such effect could be attributed to hepatoprotective properties, antiproliferative activity and antiangiogenic potential

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

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

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe