Regulatory natural killer cell expression in atopic childhood asthma

Introduction: Different subsets of natural killer (NK) cells were found to play a role in pathogenesis of allergy. We sought to investigate the expression of regulatory NK cells (CD56+CD16+CD158+) in atopic children with bronchial asthma in order to outline the value of these cells as biomarkers of disease severity and/or control.Methods: A cross sectional controlled study was carried out in the Pediatric Allergy and Immunology Unit, Ain Shams University. The study included 45 atopic children [mean age(SD)= (2.9) years] with bronchial asthma (BA) and/or allergic rhinitis (AR)as well as 40 healthy matched controls. Enrolled subjects underwent complete blood counting and flow cytometric measurement of NK cell (CD16+ CD56+) and regulatory NK cells (CD16+CD56+CD158+).Results: Patients had significantly higher regulatory NK cell percentages [mean (SD)= 41 (52) %] than controls [mean (SD)=15 (7.1)]; p≤0.001. Regulatory NK cell counts and percentages did not vary with the concomitant presence of AR or the degree of asthma control. Regulatory NK cell counts tended to be higher in children with moderate/severe BA compared to those with mild asthma but the difference did not reach statistical significance (U= -1.8, p=0.06). NK cell counts [mean (SD)= 159 (164) cells/μl] and percentages [mean (SD)= 3.7 (3.2) %] were comparable among patients and controls and did not vary with the presence of AR (p= 0.51, 0.95) or with the degree of asthma control. NK cells absolute counts and percentages tended to be higher among patients with moderate/severe compared to mild asthma but the difference did not reach statistical significance.Conclusions: Regulatory NK cells seem to be increased in childhood asthma. We recommend wider scale prospective studies on steroid-naïve subjects involving measurement of cytokines that are secreted by different types of NK cells.Keywords: Natural killer, regulatory, asthma, children, allerg

Surveillance on A/H5N1 virus in domestic poultry and wild birds in Egypt

The endemic H5N1 high pathogenicity avian influenza virus (A/H5N1) in poultry in Egypt continues to cause heavy losses in poultry and poses a significant threat to human health. Here we describe results of A/H5N1 surveillance in domestic poultry in 2009 and wild birds in 2009-2010. Tracheal and cloacal swabs were collected from domestic poultry from 22024 commercial farms, 1435 backyards and 944 live bird markets (LBMs) as well as from 1297 wild birds representing 28 different types of migratory birds. Viral RNA was extracted from a mix of tracheal and cloacal swabs media. Matrix gene of avian influenza type A virus was detected using specific real-time reverse-transcription polymerase chain reaction (RT-qPCR) and positive samples were tested by RT- qPCR for simultaneous detection of the H5 and N1 genes. In this surveillance, A/H5N1 was detected from 0.1% (n = 23/) of examined commercial poultry farms, 10.5% (n = 151) of backyard birds and 11.4% (n = 108) of LBMs but no wild bird tested positive for A/H5N1. The virus was detected from domestic poultry year- round with higher incidence in the warmer months of summer and spring particularly in backyard birds. Outbreaks were recorded mostly in Lower Egypt where 95.7% (n = 22), 68.9% (n = 104) and 52.8% (n = 57) of positive commercial farms, backyards and LBMs were detected, respectively. Higher prevalence (56%, n = 85) was reported in backyards that had mixed chickens and waterfowl together in the same vicinity and LBMs that had waterfowl (76%, n = 82). Our findings indicated broad circulation of the endemic A/H5N1 among poultry in 2009 in Egypt. In addition, the epidemiology of A/H5N1 has changed over time with outbreaks occurring in the warmer months of the year. Backyard waterfowl may play a role as a reservoir and/or source of A/H5N1 particularly in LBMs. The virus has been established in poultry in the Nile Delta where major metropolitan areas, dense human population and poultry stocks are concentrated. Continuous surveillance, tracing the source of live birds in the markets and integration of multifaceted strategies and global collaboration are needed to control the spread of the virus in Egypt

LISTERIA MONOCYTOGENESIN RAW MILK AND DAIRY PRODUCTS;OCCURRENCE AND TRIALS FOR THEREDUCTION OF THEIR RESISTANCE TO ANTIBIOTICS.

Listeria monocytogenes is a facultative intracellular pathogen responsible for severe infection in animals and humans. This study aimed to determine the occurrence of Listeriamonocytogenes in 200 samples of raw milk and dairy products marketed in Egypt, with detection the antimicrobial resistance profiles of the isolates for different antimicrobial agents. The synergistic effects of three plant extracts in combination with the used antimicrobials to control resistant L. monocytogenes isolates were assessed, with evaluation of relationship between the antibacterial activity and composition of plant extracts. A total of 5 (2.5%) L. monocytogenes isolates were identified (3 isolates from raw milk and two isolates from kariesh cheese and ice cream, one each). The isolates were sensitive to ciprofloxacin and sulphadimidine, while for amoxicillin and oxytetracycline, were resistant. The higher antimicrobial effects of basil and cinnamon extracts were detected, in addition, low concentrations of them were enough to show synergistic effect with the amoxicillin and oxytetracycline to control resistant isolates, these might be attributable to their chemical compositions. In conclusion, there is need for effectively pasteurized raw milk consumption or usage in the production of dairy products. In addition, the chemical composition of these plant extracts might help in its use to control resistant isolates with appropriate antibiotics without the need for increasing the used dosage doses

Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species.

Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules

Vorinostat with Sustained Exposure and High Solubility in Poly(ethylene glycol)-b-poly(DL-lactic acid) Micelle Nanocarriers: Characterization and Effects on Pharmacokinetics in Rat Serum and Urine

The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anti-cancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat’s pharmacokinetics in rats were investigated after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) micellar administrations and compared to a conventional PEG400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 mg/ml to 8.15 ± 0.60 mg/ml and 10.24 ± 0.92 mg/ml at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 nm and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19 %, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the oral and intravenous pharmacokinetics and bioavailability of vorinostat, which warrants further investigation

Ultra-wide-field retinal imaging in the management of non-infectious retinal vasculitis.

BACKGROUND: The purpose of this study is to describe and quantify the benefit of ultra-wide-field imaging and fluorescein angiography (FA) in the management of non-infectious retinal vasculitis. In this prospective observational cohort series, patients with non-infectious retinal vasculitis were evaluated and enrolled by four investigators from the Divisions of Retina and Ocular Immunology at the Wilmer Eye Institute. In each patient, disease activity and the need for management changes were assessed, based on clinical examination with or without standard (60°) imaging and then with the addition of ultra-wide-field pseudo-color scanning laser ophthalmoscope (SLO) images and FA using the Optos ultra-wide-field SLO (Optos Panoramic 200MA™, Optos PLC, Dunfermline, Scotland, UK). A standardized questionnaire was completed by each investigator at the time of the clinical evaluation.The primary outcome was the percentage of patients whose management was changed by clinical examination and standard FA, compared with clinical examination plus ultra-wide-field imaging. The secondary outcome was the percentage of patients whose disease was determined to be active based on each modality. RESULTS: Seventy-one visits from 23 patients were reviewed and analyzed. Based on examination plus ultra-wide-field imaging and ultra-wide-field angiography, disease activity was detected in 48/71 (68%) compared with 32/71 (45%) based on examination and standard FA (P = 0.0095). Based on the clinical examination alone, the decision to alter management was made in 4 of 71 visits (6%), and an additional 3 of 71 (4%) based on simulated standard FA. The addition of ultra-wide-field SLO pseudo-color images altered management in an additional 10/71 visits (14%), and 36/71 (51%) with the addition of ultra-wide-field FA. CONCLUSIONS: Ultra-wide-field fluorescein imaging and angiography can provide additional information that may be important and relevant in the management of retinal vasculitis

LOCUS OF CONTROL THEORY IN TREATING TOURIST BEHAVIOR: THE THEORY ROOTS AND RESEARCH DIRECTION IN DESTINATION BRANDING FIELD

We aim to shed light on this issue by reviewing the roots and development of the locus of control theory. Moreover, we will introduce how we can use this development, in theory, to provide a new research direction in the tourism service field. A theory-based review was conducted to investigate the locus of control theory roots and its potential implications in the tourism industry using the Australian Business Deans Council (ABDC) list to explore the current literature. We followed the PRISMA methodology to collect the data from the Scopus database as well as Google Scholar and ResearchGate. The study found that the locus of control theory has its roots in social psychology and has been developed over the years to explain individual differences in behavior and decision-making. In the tourism service field, we found that understanding the locus of control can help service providers tailor their services to meet the needs and expectations of different types of tourists. This will contribute to attribution literature in psychological aspects and tourism literature with a deep understanding of how tourists behave and interpret differently

Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the state of Qatar

Background: Human Papilloma Virus (HPV) infection is the major cause of cervical cancer worldwide. With limited data available on HPV prevalence in the Arab countries, this study aimed to identify the prevalence and genotypic distribution of HPV in the State of Qatar. Methods: 3008 cervical samples, exclusively of women with Arabic origin residing in Qatar were collected from the Women’s Hospital and Primary Health Care Corporation in Doha, State of Qatar. HPV DNA detection was done using GP5+/6+ primers based real time-polymerase chain reaction (RT-PCR) assay followed by the usage of HPV type specific primers based RT- PCR reactions and Sanger sequencing for genotype identification. Results: Similar prevalence rates of HPV infection was identified in both Qatari and non-Qatari women at 6.2% and 5.9% respectively. HPV prevalence rate of 5.8% and 18.4% was identified in women with normal cytology and in women with abnormal cytology respectively. HPV 81, 11 and 16, in decreasing order were the most commonly identified genotypes. HPV 81 was the most frequent low-risk genotype among women with both normal (74.0%) and abnormal (33.3%) cytology. HPV 16 (4.6%) was identified as the predominant high-risk HPV genotype among women with normal cytology and HPV 16, HPV 18, and HPV 56 (22.2% each) were the most common identified high-risk genotypes in women with abnormal cytology Conclusions: The overall HPV prevalence in Arab women in Qatar was identified as 6.1% with an increased HPV prevalence seen in women with abnormal cytology results and no significant trends seen with age. In contrast to Western countries, we report a varied genotypic profile of HPV with a high prevalence of low-risk HPV genotype 81 among the Arab women residing in Qatar.Weill Cornell Medical College in Qatar; and by a grant from the Qatar National Research Fund (NPRP- 09-344-3-082)

Epigenetic modifiers induce bioactive phenolic metabolites in the marine-derived fungus penicillium brevicompactum

Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 1–9. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC50 20 to 30 µg/mL) and antiproliferative activities (IC50 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a pharmacophore model of the active compounds was generated to build up a structure-activity relationship