ABSTRACT
INTRODUCTION: Lack of recent data on asthma control in Algeria led to this study whose results were compared with those of the same study conducted in the Middle East and North Africa (MENA). METHOD: This cross-sectional epidemiological study was performed in adults who had been diagnosed with asthma for at least one year and without exacerbation within the last 4 weeks. Asthma control was assessed using the 2012 Global Initiative for Asthma (GINA) criteria and the Asthma control test (ACT) questionnaire. RESULTS: We studied 984 patients mainly managed by specialist physicians; 61% female, mean age 45 years, body mass index 27kg/m2, active smokers 2%. Medication was prescribed in 92% with 78% receiving inhaled corticosteroids alone or with add-on therapies. Good adherence was observed in 27%. Asthma control was observed in 34.6% vs. 28.6% in other countries (P < 0.001). Low level of education, absence of medical insurance, lack of physical exercise, and-long duration of the disease were significantly associated with uncontrolled asthma. CONCLUSION: Poor control of asthma is still observed in Algeria despite a high level of specialist involvement. Except for adherence, known predictive factors of poor asthma control have been observed. Quality improvement training of health care professionals and patient education are probably the main issues to be addressed.
Subject(s)
Asthma/epidemiology , Asthma/therapy , Medication Adherence/statistics & numerical data , Administration, Inhalation , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adult , Africa, Northern/epidemiology , Aged , Algeria/epidemiology , Asthma/pathology , Cross-Sectional Studies , Disease Progression , Female , Humans , Male , Middle Aged , Middle East/epidemiology , Smoking/adverse effects , Smoking/epidemiology , Smoking Cessation/statistics & numerical data , Treatment Outcome , Young AdultABSTRACT
The BH3 mimetic ABT737 induces autophagy by competitively disrupting the inhibitory interaction between the BH3 domain of Beclin 1 and the anti-apoptotic proteins Bcl-2 and Bcl-X(L), thereby stimulating the Beclin 1-dependent allosteric activation of the pro-autophagic lipid kinase VPS34. Here, we examined whether ABT737 stimulates other pro-autophagic signal-transduction pathways. ABT737 caused the activating phosphorylation of AMP-dependent kinase (AMPK) and of the AMPK substrate acetyl CoA carboxylase, the activating phosphorylation of several subunits of the inhibitor of NF-κB (IκB) kinase (IKK) and the hyperphosphorylation of the IKK substrate IκB, inhibition of the activity of mammalian target of rapamycin (mTOR) and consequent dephosphorylation of the mTOR substrate S6 kinase. In addition, ABT737 treatment dephosphorylates (and hence likewise inhibits) p53, glycogen synthase kinase-3 and Akt. All these effects were shared by ABT737 and another structurally unrelated BH3 mimetic, HA14-1. Functional experiments revealed that pharmacological or genetic inhibition of IKK, Sirtuin and the p53-depleting ubiquitin ligase MDM2 prevented ABT737-induced autophagy. These results point to unexpected and pleiotropic pro-autophagic effects of BH3 mimetics involving the modulation of multiple signalling pathways.
Subject(s)
Apoptosis Regulatory Proteins/agonists , Autophagy/drug effects , Biphenyl Compounds/pharmacology , Membrane Proteins/agonists , Nitrophenols/pharmacology , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Sulfonamides/pharmacology , Acetyl-CoA Carboxylase/metabolism , Beclin-1 , Benzopyrans/pharmacology , Cell Line, Tumor , Glycogen Synthase Kinase 3/metabolism , Humans , I-kappa B Kinase/metabolism , Nitriles/pharmacology , Oncogene Protein v-akt/metabolism , Phosphorylation , Phosphotransferases (Phosphate Group Acceptor)/metabolism , Piperazines/pharmacology , Proto-Oncogene Proteins c-mdm2/metabolism , Ribosomal Protein S6 Kinases/metabolism , Signal Transduction/drug effects , Sirtuins/metabolism , TOR Serine-Threonine Kinases/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
Genetic polymorphisms in neuronal nitric oxide synthase (NOS1) and calmodulin-dependent endothelial NOS (NOS3) genes are known to influence the course of allergic respiratory disorders. We investigated the role of NOS1 -84 G-->A and NOS3 -786 T-->C, 894 G-->T and 27 base pair (bp) repeat polymorphisms in 125 patients suffering from asthma and/or rhinitis and monosensitized against Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. We found a higher frequency of the -786 C NOS3 allele in patients than in controls [corrected P value (Pc) = 0.04], especially in female cases (Pc = 0.02) and that the 'ab' genotype of the 27-bp polymorphism was significantly associated with specific immunoglobulin E production against Dpter (P = 0.006). This study brings further support for the participation of NOS3 gene polymorphism in the pathogenesis of respiratory allergic disorders.
Subject(s)
Dermatophagoides pteronyssinus/immunology , Genetic Predisposition to Disease , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type I/genetics , Respiratory Hypersensitivity/genetics , Adolescent , Adult , Algeria , Animals , Female , Humans , Male , Polymorphism, GeneticABSTRACT
Circulation antigen and sera antibodies were measured in 122 sera obtained from 87 patients with proved hydatic echinococcosis: the sera were obtained before and after surgical treatment. Circulating antigen was detected by E. L. I. S. A., and was present in 21% of the sera. Antibodies were present by conterimmunoelectrophoresis in 56%, by haemagglutination in 72%, E. L. I. S. A. IgG in 87%, E. L. I. S. A. IgM in 54%, E. L. I. S. A. IgA in 53%, E. L. I. S. A. IgE in 25% of the sera. No evident correlations between these results and the localisation could be found, nor with anatomical integrity of the cyst, or the surgical treatment date. Only the presence of IgE or circulating antigen could suggest the high level passage of hydatic proteins, bringing to mind a fissuration of the cyst wall.
