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1.
Toxicol Sci ; 199(2): 276-288, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38526216

ABSTRACT

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high affinity ligand for the aryl hydrocarbon receptor (AhR). In animal models, AhR activation by TCDD generally inhibits antibody secretion. However, it is less clear if this translates to human antibody production. Using a human Burkitt lymphoma B-cell line (CL-01) that can be stimulated to secrete Ig and undergo class switch recombination to other Ig isotypes, the current study evaluated the effects of AhR activation or antagonism on the human Ig isotypic expression profile with CD40L+IL-4 stimulation. Our results suggest that AhR agonists (TCDD and indirubin) have little to no effect on IgM or IgA secretion, which were also not induced with stimulation. However, AhR activation significantly inhibited stimulation-induced IgG secretion, an effect reversed by the AhR antagonist CH223191. Evaluation of Ig heavy chain (IgH) constant region gene expression (ie Cµ, Cγ1-4, Cα1-2, and Cε that encode for IgM, IgG1-4, IgA1-2, and IgE, respectively) demonstrated differential effects. While Cµ and Cα2 transcripts were unaffected by stimulation or AhR agonists, AhR activation significantly inhibited stimulation-induced Cγ2-4 and Cε mRNA transcripts, which was reversed by AhR antagonism. Notably, AhR antagonism in the absence of exogenous AhR ligands significantly increased IgG and IgA secretion as well as the expression of Cγ2-4 and Cε. These results suggest that modulation of AhR activity differentially alters the IgH isotypic expression profile and antibody secretion that may be partly dependent on cellular stimulation. Since a variety of chemicals from anthropogenic, industrial, pharmaceutical, dietary, and bacterial sources bind the AhR, the ability of environmental exposures to alter AhR activity (i.e. activate or inhibit) may have a direct influence on immune function and antibody-relevant disease conditions.


Subject(s)
B-Lymphocytes , Immunoglobulin Isotypes , Polychlorinated Dibenzodioxins , Receptors, Aryl Hydrocarbon , Receptors, Aryl Hydrocarbon/agonists , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/genetics , Humans , Polychlorinated Dibenzodioxins/toxicity , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Immunoglobulin Isotypes/immunology , Immunoglobulin Isotypes/genetics , Cell Line, Tumor , Indoles/pharmacology , CD40 Ligand/immunology , CD40 Ligand/metabolism , Immunoglobulin Class Switching/drug effects , Environmental Pollutants/toxicity , Basic Helix-Loop-Helix Transcription Factors
2.
J Egypt Public Health Assoc ; 85(1-2): 61-71, 2010.
Article in English | MEDLINE | ID: mdl-21073848

ABSTRACT

BACKGROUND: Tuberculosis (TB) infection represents a global health problem and a great risk to Health Care Workers (HCWs). Identifying individuals, particularly HCWs with latent tuberculosis infection (LTBI) will support TB control through chemoprophylaxis and prevent cross-infection. OBJECTIVES: This study aimed to identify prevalence of Latent TB among a two-year new hires of HCWs in 4 major tertiary care hospitals in Riyadh, Saudi Arabia. MATERIAL AND METHODS: 2650 recently (2-years) hired HCWs were surveyed for latent TB using Tuberculin Skin Test (TST). Data was collected from January 2008 to December 2009. Induration due to TST equal to or more than 10 mm. within 48-72 hours was considered positive. The results of TST were correlated with other variables such as age group, gender, job category, country of origin. RESULTS: as an overall rate, 291(11%) out of 2650 were positive for TST, with the highest significant positive rates among physicians (14.9%) and nurses (12.9%) compared to students as a reference group. No statistically significant difference was detected between both sexes. The highest significant positive TST rates were found among HCWs in the age group of 50 years and older (32.6%) compared to 10-19 years age group as a reference group, and among HCWs coming from sub-Saharan countries (61.1%) compared to Saudi HCWs with the lowest positive rates (5%) as a reference group. CONCLUSION AND RECOMMENDATIONS: LTB is prevalent among newly hired HCWs in Riyadh tertiary hospitals. Standard programs for detection and treatment of LTB should be encouraged.


Subject(s)
Latent Tuberculosis/epidemiology , Personnel, Hospital/statistics & numerical data , Adolescent , Adult , Female , Humans , Male , Middle Aged , Prevalence , Saudi Arabia/epidemiology , Young Adult
3.
Saudi Med J ; 29(1): 102-6, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18176683

ABSTRACT

OBJECTIVE: To estimate levels and trends, gender differentials, effect of modes of living, regional differentials, and the effect of parental educational on infant and child mortality. METHODS: A nationwide stratified random sample was used to estimate levels, trends and differentials of infant and child mortality in Saudi Arabia. The study was executed during the period February 2006 to June 2006 and covered all the 20 health regions of Saudi Arabia. The randomly selected sample was limited to ever married Saudi women in the reproductive age group (15-49 years). RESULTS: The findings show a continuous and considerable infant and child mortality decline during the 1994-2004 period. The infant mortality rate has decline from 22 per 1,000 live births in 1994 to 17 per 1,000 live births in 2004; while the child mortality rate has declined from 34 to 22 per 1,000 live births in the same period. There is a strong relation between infant and child mortality and the mode of living and parental education. CONCLUSION: The study proves the continuous decline of infant and child mortality during the study period and affirms the effect of parental education on these indicators.


Subject(s)
Child Mortality/trends , Infant Mortality/trends , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Risk Factors , Saudi Arabia/epidemiology , Surveys and Questionnaires
4.
Genet Med ; 9(6): 372-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17575503

ABSTRACT

PURPOSE: To estimate the prevalence of sickle cell disorders and beta thalassemia, with their regional distribution, in the adult population screened as part of the Saudi Premarital Screening Program. METHODS: A cross-sectional, population-based study was conducted as part of the National Premarital Screening Program. It covered all the individuals who applied for a marriage license during the years 1425 and 1426 Hijra (February 2004 to January 2005). A network of 123 reception centers in the Ministry of Health facilities and 70 laboratories all over Saudi Arabia was involved in data collection. RESULTS: Of a total of 488,315 individuals screened, 4.20% had sickle cell trait, 0.26% had sickle cell disease, 3.22% had thalassemia trait, and 0.07% had thalassemia disease. Both the diseases were focused mainly in the eastern, western, and southwestern parts of the country. Among the 207,333 couples who were issued certificates for matching, 2.14% were declared high risk. Among the 2,375 high-risk couples contacted by telephone, 89.6% married each other, despite the known high-risk status. CONCLUSION: The results showed excellent access to the target population. However, the program's objective of decreasing high-risk marriages was not as successful, indicating the need for improvement of health education programs for the public, more efforts in counseling high risk couples, and changes in the strategy of timing of screening in relation to marriage.


Subject(s)
Anemia, Sickle Cell/genetics , Genetic Testing , Premarital Examinations , Thalassemia/genetics , Anemia, Sickle Cell/epidemiology , Female , Humans , Male , Saudi Arabia , Thalassemia/epidemiology
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