Respiratory effects of environmental tobacco exposure are enhanced by bronchial hyperreactivity

RATIONALE: Exposure to environmental tobacco smoke (ETS) is associated with increased reports of respiratory symptoms and reduced lung function, but the long-term effects of ETS are unclear, notably in healthy individuals with bronchial hyperresponsiveness (BHR). OBJECTIVE: To assess the longitudinal effects of ETS exposure on the development of respiratory symptoms and spirometry in subjects with BHR. METHODS: The study population included 1,661 never-smokers from the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cohort, assessed in 1991 (baseline) and 11 yr later, who were symptom-free at baseline. Incident reports of respiratory symptoms and results of spirometry were assessed at the follow-up survey. MAIN RESULTS: Exposure to ETS reported in the two surveys was strongly associated with the development of cough (odds ratio, 2.1; 95% confidence interval, 1.2-3.7; p = 0.01). In subjects with BHR exposed to ETS at both surveys, a trend for strong associations were observed for wheeze, cough, dyspnea, and chronic bronchitis; however, the association reached statistical significance only for the symptom of dyspnea (p < 0.01). Lower FEV1/FVC (mean +/- SD, 72.9 +/- 7.7 vs. 76.8 +/- 6.1%; p < 0.01) and FEF(25-75) (forced expiratory flow, midexpiratory phase)/FVC (mean +/- SD, 56.1 +/- 22.5 vs. 68.1 +/- 21.6%; p < 0.01) were observed in subjects with BHR exposed to ETS compared with nonexposed subjects without BHR. Lower values were found in subjects continuing exposure by the follow-up survey. CONCLUSION: Exposure to ETS was strongly associated with the development of respiratory symptoms in previously asymptomatic subjects with BHR within 11 yr. Furthermore, subjects with underlying BHR had reduced lung function at follow-up, thus suggesting a higher risk for the development of chronic respiratory disease in this subset of the population.     

Detection of HIV type 1 non-B subtypes in Sicily, Italy

To evaluate the presence of HIV-1 non-B subtypes in Sicily, we sequenced and genotyped HIV-1 PR and RT regions of the pol gene using plasma from 169 HIV-1-infected adult patients. All samples were obtained from a study of antiretroviral-associated resistance mutations resulting in virological failure during highly active antiretroviral therapy (HAART). Eight (4.7%) patients had the non-B HIV-1 subtype including some circulating recombinant forms (CRFs). All of these individuals acquired the infection by heterosexual transmission. The detection of HIV-1 non-B strains was significantly associated with younger age of HIV-1 acquisition. Our findings indicate, for the first time, the presence of HIV-1 non-B subtypes in Sicily in patients who experienced virological failure during HAART, and highlight the need for implementing a network for the epidemiological surveillance of HIV-1 subtypes in Southern Europe.     

High Level of Cross-Resistance between Kanamycin,Amikacin, and Capreomycin among Mycobacterium tuberculosis Isolates from Georgia and a Close Relation with Mutations in the rrs Gene

The aminoglycosides kanamycin and amikacin and the macrocyclic peptide capreomycin are key drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB). The increasing rates of resistance to these drugs and the possible cross-resistance between them are concerns for MDR-TB therapy. Mutations in the 16S rRNA gene (rrs) have been associated with resistance to each of the drugs, and mutations of the tlyA gene, which encodes a putative rRNA methyltransferase, are thought to confer capreomycin resistance in Mycobacterium tuberculosis bacteria. Studies of possible cross-resistance have shown variable results. In this study, the MICs of these drugs for 145 clinical isolates from Georgia and the sequences of the rrs and tlyA genes of the isolates were determined. Of 78 kanamycin-resistant strains, 9 (11.5%) were susceptible to amikacin and 16 (20.5%) were susceptible to capreomycin. Four strains were resistant to capreomycin but were susceptible to the other drugs, whereas all amikacin-resistant isolates were resistant to kanamycin. Sequencing revealed six types of mutations in the rrs gene (A514C, C517T, A1401G, C1402T, C1443G, T1521C) but no mutations in the tlyA gene. The A514C, C517T, C1443G, and T1521C mutations showed no association with resistance to any of the drugs. The A1401G and C1402T mutations were observed in 65 kanamycin-resistant isolates and the 4 capreomycin-resistant isolates, respectively, whereas none of the susceptible isolates showed either of those mutations. The four mutants with the C1402T mutations showed high levels of resistance to capreomycin but no resistance to kanamycin and amikacin. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to kanamycin and amikacin, while the sensitivities reached 85.9% and 94.2%, respectively.Although the first-line anti-tuberculosis (anti-TB) drugs rifampin (RMP; rifampicin), isoniazid (INH), ethambutol (EMB), pyrazinamide (PZA), and streptomycin (SM) were discovered several decades ago, they are still used today in standard short-course regimens for the treatment of TB. These regimens are, however, ineffective for the treatment of multidrug-resistant (MDR) TB (defined as resistance to at least the two most powerful anti-TB drugs, RMP and INH), leading to the use of less effective and more toxic second-line drugs (SLDs). Injectable drugs such as kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) are the key SLDs for the treatment of MDR-TB (17). The emergence of extensively drug-resistant TB, defined as MDR-TB with additional resistance to any fluoroquinolone and at least one of the injectable drugs (10), once again underlines the importance of fast and reliable testing for susceptibility to these antibiotics.Mutations in the 3′ part of the 16S rRNA gene (rrs), particularly at positions 1401, 1402, and 1484 (1, 7, 11, 12), have been associated with resistance to each of the drugs. It has also been suggested that mutations in the tlyA gene are responsible for resistance to CAP (8). Additionally, reports of cross-resistance among various aminoglycosides and CAP have been variable (1, 4, 6, 16). Most of the previous investigations were done with laboratory-generated mutants and with only a limited number of clinical isolates. In this work, we investigated the correlation between mutations in the rrs and tlyA genes and the in vitro resistance to the three injectable drugs of clinical Mycobacterium tuberculosis isolates.     

Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways

Substance P (SP), encoded by the tachykinin 1 (Tac1) gene, is the most potent tachykinin ligand for the high-affinity neurokinin-1 receptor (NK-1R). We previously reported that NK-1R-deficient mice show less weight gain and reduced circulating levels of leptin and insulin in response to a high-fat diet (HFD) and demonstrated the presence of functional NK-1R in isolated human preadipocytes. Here we assessed the effects of SP on weight gain in response to HFD and determined glucose metabolism in Tac1-deficient (Tac1(-/-)) mice. The effect of SP on the expression of molecules that may predispose to reduced glucose uptake was also determined in isolated human mesenteric, omental, and sc preadipocytes. We show that although weight accumulation in response to HFD was similar between Tac1(-/-) mice and wild-type littermates, Tac1(-/-) mice demonstrated lower glucose and leptin and increased adiponectin blood levels and showed improved responses to insulin challenge after HFD. SP stimulated phosphorylation of c-Jun N-terminal kinase, protein kinase C, mammalian target of rapamycin, and inhibitory serine insulin receptor substrate-1 phosphorylation in human preadipocytes in vitro. Preincubation of human mesenteric preadipocytes with the protein kinase C pseudosubstrate inhibitor reduced insulin receptor substrate 1 phosphorylation in response to SP. Lastly, SP also induced insulin receptor substrate-1 phosphorylation in mature human sc adipocytes. Our results demonstrate an important role for SP in adipose tissue responses and obesity-associated pathologies. These novel SP effects on molecules that enhance insulin resistance at the adipocyte level may reflect an important role for this peptide in the pathophysiology of type 2 diabetes.     

Prevalence of and factors influencing smoking among medical and non-medical students in Tbilisi,Georgia

OBJECTIVE:

Smoking is a serious problem that has a devastating impact on health. The objective of this study was to describe the prevalence of and factors influencing smoking among medical and non-medical students in Tbilisi, Georgia, as well as to determine whether medical education has an impact on smoking.

METHODS:

A cross-sectional study was carried out at Tbilisi State Medical University and Tbilisi State University, both of which are located in Tbilisi, Georgia. A total of 400 4th-year students (200 students at each university) were asked to complete standardized questionnaires.

RESULTS:

Of the sample as a whole, 48.75% were identified as smokers and 51.25% were identified as nonsmokers. The mean age was 20.24 years among smokers and 20.26 years among nonsmokers. Of the medical students, 49.5% were smokers, as were 48.0% of the non-medical students. The male-to-female ratio in the study population was 0.9:1.1. Smoking was found to have a strong relationship with gender, males accounting for 65% of all smokers. Of the smokers, 56.9% stated that they would like to quit smoking (for health or financial reasons). Of the medical students, 59.5% expressed a willingness to quit smoking, as did 54.2% of the non-medical students.

CONCLUSIONS:

There is a need to improve smoking education for undergraduate students. Special attention should be given to the inclusion of anti-smoking education in undergraduate curricula, as well as to the implementation of smoking prevention campaigns at institutions of higher education. However, such measures will be effective only if tobacco control policies are strictly enforced on the national level as well.     

Costs of childhood asthma due to traffic-related pollution in two California communities

Recent research suggests the burden of childhood asthma that is attributable to air pollution has been underestimated in traditional risk assessments, and there are no estimates of these associated costs. We aimed to estimate the yearly childhood asthma-related costs attributable to air pollution for Riverside and Long Beach, CA, USA, including: 1) the indirect and direct costs of healthcare utilisation due to asthma exacerbations linked with traffic-related pollution (TRP); and 2) the costs of health care for asthma cases attributable to local TRP exposure. We calculated costs using estimates from peer-reviewed literature and the authors' analysis of surveys (Medical Expenditure Panel Survey, California Health Interview Survey, National Household Travel Survey, and Health Care Utilization Project). A lower-bound estimate of the asthma burden attributable to air pollution was US$18 million yearly. Asthma cases attributable to TRP exposure accounted for almost half of this cost. The cost of bronchitic episodes was a major proportion of both the annual cost of asthma cases attributable to TRP and of pollution-linked exacerbations. Traditional risk assessment methods underestimate both the burden of disease and cost of asthma associated with air pollution, and these costs are borne disproportionately by communities with higher than average TRP.