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Sample records for active pulmonary tb

  1. Gene expression profiles of bronchoalveolar cells in Pulmonary TB

    PubMed Central

    Raju, Bindu; Hoshino, Yoshihiko; Belitskaya-Lévy, Ilana; Dawson, Rod; Ress, Stanley; Gold, Jeffrey A.; Condos, Rany; Pine, Richard; Brown, Stuart; Nolan, Anna; Rom, William N.; Weiden, Michael D.

    2008-01-01

    The host response to Mycobacterium tuberculosis includes macrophage activation, inflammation with increased immune effector cells, tissue necrosis and cavity formation, and fibrosis, distortion, and bronchiectasis. To evaluate the molecular basis of the immune response in the lungs of patients with active pulmonary tuberculosis (TB), we used bronchoalveolar lavage to obtain cells at the site of infection. Affymetrix Genechip micro-arrays and cDNA nylon filter microarrays interrogated gene expression in BAL cells from 11 healthy controls and 17 patients with active pulmonary TB. We found altered gene expression for 69 genes in TB versus normal controls that included cell surface markers, cytokines, chemokines, receptors, transcription factors, and complement components. In addition, TB BAL cell gene expression patternssegregated into 2 groups: one suggestive of a T helper type 1 (Th1) cellular immune response with increased STAT-4, IFN-γ receptor, and MIG expression with increased IFN-γ protein levels in BAL fluid; the other group displayed characteristics of Th2 immunity with increased STAT-6, CD81, and IL-10 receptor expression. We were able to demonstrate that a Th2 presentation could change to a Th1 pattern after anti-tuberculous treatment in one TB patient studied serially. These gene expression data support the conclusion that pulmonary TB produces a global change in the BAL cell transcriptome with manifestations of either Th1 or Th2 immunity. PMID:17921069

  2. Hyponatremia in pulmonary TB: evidence of ectopic antidiuretic hormone production.

    PubMed

    Lee, Paul; Ho, Ken K Y

    2010-01-01

    Hyponatremia is among the most common biochemical abnormalities in hospital inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of several causes of hyponatremia, particularly in patients with pulmonary diseases. The mechanism of SIADH associated with pulmonary infection is, however, poorly understood. We report an unusual case of hyponatremia in a man with pulmonary TB and central diabetes insipidus with biochemical evidence of ectopic antidiuretic hormone production as a possible mechanism causing hyponatremia.

  3. The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis

    PubMed Central

    Blankley, Simon; Graham, Christine M.; Turner, Jacob; Berry, Matthew P. R.; Bloom, Chloe I.; Xu, Zhaohui; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; Breen, Ronan; Santis, George; Blankenship, Derek M.; Lipman, Marc; O’Garra, Anne

    2016-01-01

    Background Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. Methods A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB. Results The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. Conclusions The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics. PMID:27706152

  4. The frequency distribution of vitamin D Receptor fok I gene polymorphism among Ugandan pulmonary TB patients

    PubMed Central

    Acen, Ester L.; Worodria, William; Mulamba, Peter; Kambugu, Andrew; Erume, Joseph

    2016-01-01

    Background: Mycobacterium tuberculosis (TB) is still a major problem globally and especially in Africa. Vitamin D deficiency has been linked to TB in the past and studies have found vitamin D deficiency to be common among Ugandan TB patients. The functional activity of vitamin D is dependent on the genotype of the vitamin D receptor (VDR) polymorphic genes. Recent findings have indicated that VDR polymorphisms may cause increased resistance or susceptibility to TB. The vitamin D ligand and its receptor play a pivotal role in innate immunity by eliciting antimicrobial activity, which is important in prevention of TB. The fok I vitamin D receptor gene has extensively been examined in TB patients but findings so far have been inconclusive. Objectives: This study sought to investigate the frequency distribution of the VDR fok I gene polymorphisms in pulmonary TB patients and controls. Methods: A pilot case control study of 41 newly diagnosed TB patients and 41 healthy workers was set up. Vitamin D receptor fok I gene was genotyped. Results: The frequency distribution of fok I genotype in Ugandan TB patients was 87.8% homozygous-dominant (FF), 7.3% (Ff) heterozygous and 4.8% (ff) homozygous recessive. For normal healthy subjects the frequencies were (FF) 92.6%, (Ff) 2.4% and (ff) 4.8%. No significant difference was observed in the FF and ff genotypes among TB patients and controls. The Ff heterozygous genotype distribution appeared more in TB patients than in controls. A significant difference was observed in the fok I genotype among gender p value 0.02. No significant difference was observed in ethnicity, p value 0.30. Conclusions: The heterozygous Ff fok I genotype may be associated with TB in the Ugandan population. PMID:27785354

  5. Use of the QuantiFERON-TB Gold In-Tube Test in the Diagnosis and Monitoring of Treatment Efficacy in Active Pulmonary Tuberculosis

    PubMed Central

    Chang, Ping-Chin; Wang, Pin-Hui; Chen, Kow-Tong

    2017-01-01

    The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment. PMID:28264462

  6. Risk Factors for Primary Pulmonary TB in Almaty Region, Kazakhstan: A Matched Case-Control Study

    PubMed Central

    ZHUSSUPOV, Baurzhan; HERMOSILLA, Sabrina; TERLIKBAYEVA, Assel; AIFAH, Angela; MA, Xin; ZHUMADILOV, Zhaxybay; ABILDAYEV, Tleukhan; DARISHEVA, Meruyert; BERIKKHANOVA, Kulzhan

    2016-01-01

    Background: This study examined the association between incident pulmonary tuberculosis (TB) and social and behavioral characteristics in Almaty Oblast, Kazakhstan from 2012 to 2013. Methods: We used a matched case-control design to estimate the role of factors for acquiring pulmonary TB. Totally 324 individuals were recruited from Sep 2012 to Mar 2013. Participants included 110 TB index cases with newly detected pulmonary TB. Each case was matched with one household and one community control. A total of 107 household and 107 community controls were included to the study. Adjusted odds ratios measuring associations between TB and risk factors were calculated by using a conditional multiple logistic regression analysis. Results: TB cases were more likely to be younger, recent smokers and have diabetes, when compared to household controls. Between TB cases and community controls, TB was significantly associated with age, non-married family status, living in a rented home, recent smoker, and having diabetes. Comparing TB cases with community controls, we found that foreign birth was marginally associated with incident TB case status. Conclusion: Our findings confirm the role of modifiable risk factors for TB in Kazakhstan; highlighting the importance of developing interventions addressing social determinants and proximate risk factors for high TB burden regions. PMID:27252913

  7. Difference Between Latent TB Infection and Active TB Disease

    MedlinePlus

    ... person with infectious TB coughs or sneezes, droplet nuclei containing M. tuberculosis are expelled into the air. If another person inhales air containing these droplet nuclei, he or she may become infected. However, not ...

  8. PULMONARY TB AMONG MYANMAR MIGRANTS IN SAMUT SAKHON PROVINCE, THAILAND: A. PROBLEM OR NOT FOR THE TB CONTROL PROGRAM?

    PubMed

    Wongkongdech, Ranee; Srisaenpang, Sompong; Tungsawat, Sasithorn

    2015-03-01

    Most transnational migrant workers in Thailand are from Myanmar, a country with a high tuberculosis prevalence. We investigated the prevalence of suspected pulmonary tuberculosis (TB) among Myanmar migrants in communities of Mueang District, Samut Sakhon Province, Thailand. Symptom screening for those with a productive cough of more than 2 weeks was conducted by face-to-face home interviews with 4,874 participants aged at least 15 years. Most subjects (75%) were aged 15-34 years (75%), 52% were male and 60% were married. Subjects typically lived with fellow nationals in crowded, poorly ventilated apartments or row houses. Ten subjects had suspected TB, giving a prevalence rate of 0.2%. Ninety-seven percent were working in Thailand legally but 80% had no health insurance. None had sought community health services; all preferred self-medication and private clinics due to stigma associated with TB, medication costs and health center waiting times. Providing information about health insurance and introducing TB prevention and control in this group should be considered. Further studies are needed to develop a TB control program and communicable disease surveillance among migrant communities, in Thailand.

  9. Performance of the WHO 2011 TB Symptom Screening Algorithm for Pulmonary TB Diagnosis among HIV-Infected Patients in Gondar University Referral Hospital, Ethiopia

    PubMed Central

    2016-01-01

    The new WHO 2011 guidelines on TB screening among HIV-infected individuals recommend screening using four TB symptoms (current cough, fever, weight loss, and night sweats). This study aimed to assess the performance of WHO 2011 TB symptom screening algorithm for diagnosing pulmonary TB in HIV patients and identify possible risk factors for TB. Institutional based cross-sectional study was conducted from February 2012 to November 2012. A total of 250 HIV-infected patients aged ≥18 years visiting the University of Gondar Hospital, ART clinic, were enrolled. Information about WHO TB clinical symptoms and other known risk factors for TB was collected using structured questionnaire. Spot-morning-spot sputum samples were collected and direct AFB microscopy, sputum culture, and RD9 molecular typing were performed. Statistical data analysis was performed using SPSS Version 20.0 software. Of 250 study participants, fever was reported in 169 (67.6%), whereas cough and night sweats were reported in 167 (66.8%) and 152 (60.8%), respectively. A total of 11 (4.4%) TB cases were identified. Of these, 82% (9/11) TB patients reported cough, so that the negative predictive value was 98%. In addition, 66% (158/239) TB negative patients reported cough, so that positive predictive value of cough was 5%. According to the new WHOTB symptom screening algorithm, out of 250 HIV-infected persons, 83% (5/6) have been investigated by TB symptom screening and AFB smear microscopy. Therefore, the 2011 WHO TB symptom screening tool for the diagnosis of pulmonary TB is likely to reduce the diagnostic delay and lower TB morbidity and mortality rate particularly in HIV prevalent settings. PMID:28058048

  10. Smart spotting of pulmonary TB cavities using CT images.

    PubMed

    Swanly, V Ezhil; Selvam, L; Kumar, P Mohan; Renjith, J Arokia; Arunachalam, M; Shunmuganathan, K L

    2013-01-01

    One third of the world's population is thought to have been infected with mycobacterium tuberculosis (TB) with new infection occurring at a rate of about one per second. TB typically attacks the lungs. Indication of cavities in upper lobes of lungs shows the high infection. Traditionally, it has been detected manually by physicians. But the automatic technique proposed in this paper focuses on accurate detection of disease by computed tomography (CT) using computer-aided detection (CAD) system. The various steps of the detection process include the following: (i) image preprocessing, which is done by techniques such as resizing, masking, and Gaussian smoothening, (ii) image egmentation that is implemented by using mean-shift model and gradient vector flow (GVF) model, (iii) feature extraction that can be achieved by Gradient inverse coefficient of variation and circularity measure, and (iv) classification using Bayesian classifier. Experimental results show that its perfection of detecting cavities is very accurate in low false positive rate (FPR).

  11. Comparison of tuberculin skin testing and T-SPOT.TB for diagnosis of latent and active tuberculosis.

    PubMed

    Simsek, Hulya; Alpar, Sibel; Ucar, Nazire; Aksu, Funda; Ceyhan, Ismail; Gözalan, Aysegul; Cesur, Salih; Ertek, Mustafa

    2010-03-01

    The T-SPOT.TB test does not cross-react with Bacille Calmette-Guérin or most non-tuberculosis mycobacterium species, and is based on IFN-gamma responses to Mycobacterium tuberculosis-specific antigens. The objective of this study was to compare tuberculin skin test (TST) with T-SPOT.TB results used in the diagnosis of active tuberculosis (TB) as well as latent tuberculosis infection (LTBI). A total of 136 subjects participated in three different groups (47 patients with active pulmonary TB, 47 healthy persons without M. tuberculosis exposure, and 42 hospital members with a history of close contact with active TB patients). The T-SPOT.TB sensitivity (83.0%) and the negative predictive value (NPV) (82.6%) in the diagnosis of active TB were significantly higher than those of TST. The sensitivity and NPV of the TST were 38.3 and 60.8%, respectively. The T-SPOT.TB specificity (80.9%) and positive predictive value (81.3%) were lower than those of TST (95.7 and 90.0%, respectively). The performance of T-SPOT.TB and TST for diagnosing LTBI was the same (54.8%). T-SPOT.TB was superior in terms of sensitivity (83.0%); TST detected only 18, whereas T-SPOT.TB test detected 39 out of 47 patients with active TB. T-SPOT.TB is thought to have better performance than TST due to false-negative results in diagnosing active TB. However, it is considered that large prospective longitudinal studies are needed for diagnosing LTBI.

  12. CCL2, CCL18 and sIL-4R in renal, meningeal and pulmonary TB; a 2 year study of patients and contacts.

    PubMed

    Mendez, Armando; Hernandez-Pando, Rogelio; Contreras, Salvador; Aguilar, Diana; Rook, Graham A W

    2011-03-01

    The role of Th2 cytokines and Th2-associated chemokines in tuberculosis (TB) remains controversial, though in Mexico a polymorphism causing increased production of CCL2 is a risk factor. We studied levels of the Th2-associated chemokines CCL2 and CCL18, circulating soluble IL-4 receptors (sIL-4R), IL-4 and the inhibitory splice variant of IL-4 (IL-4δ2) in a cohort of patients with pulmonary TB and their healthy contacts. These were followed for 2 years during which time 10 contacts developed pulmonary TB. Results were compared with measurements made in renal and meningeal TB, and in disease controls with bacterial pneumonias or Dengue fever that have large Th2 components. In these disease controls both chemokines were significantly raised. They were also very significantly raised in all forms of TB, irrespective of age or disease site. Levels of CCL18 were raised least in meningeal TB, and most in pulmonary patients with long histories, when levels were similar to those in disease controls. Levels of CCL2, although also raised in all three forms of TB, were negatively correlated with CCL18. We found that levels of sIL-4R were strikingly reduced in all forms of TB, particularly meningeal. Contacts who progressed could not be distinguished from contacts who remained healthy at 2 years in terms of IL-4, sIL-4R, CCL2 or CCL18. However contacts had raised expression of IL-4δ2 as previously found. These results indicate vigorous and previously unrecorded activity within the Th2 axis, and further investigation is warranted.

  13. Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study.

    PubMed

    Rakotosamimanana, Niaina; Richard, Vincent; Raharimanga, Vaomalala; Gicquel, Brigitte; Doherty, T Mark; Zumla, Alimuddin; Rasolofo Razanamparany, Voahangy

    2015-10-01

    Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ≥14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ≥14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, 95% CI 1.74-41.22; p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB.

  14. Prevalence, Risk Factors and Social Context of Active Pulmonary Tuberculosis among Prison Inmates in Tajikistan

    PubMed Central

    Winetsky, Daniel E.; Almukhamedov, Olga; Pulatov, Dilshod; Vezhnina, Natalia; Dooronbekova, Aizhan; Zhussupov, Baurzhan

    2014-01-01

    Setting Tuberculosis (TB) is highly prevalent in prisons of the former Soviet Union. Objective To understand the behavioral, demographic and biological factors placing inmates in Tajikistan at risk for active TB. Design We administered a behavioral and demographic survey to 1317 inmates in two prison facilities in Sughd province, Tajikistan along with radiographic screening for pulmonary TB. Suspected cases were confirmed bacteriologically. Inmates undergoing TB treatment were also surveyed. In-depth interviews were conducted with former prisoners to elicit relevant social and behavioral characteristics. Results We identified 59 cases of active pulmonary TB (prevalence 4.5%). Factors independently associated with increased prevalence of active TB were: HIV-infection by self-report (PR 7.88; 95%CI 3.40–18.28), history of previous TB (PR 10.21; 95%CI 6.27–16.63) and infrequent supplemental nutrition beyond scheduled meals (PR 3.00; 95%CI 1.67–5.62). Access to supplemental nutrition was associated with frequency of visits from friends and family and ability to rely on other inmates for help. Conclusion In prison facilities of Tajikistan, HIV-infection, injection drug use and low access to supplemental nutrition were associated with prevalent cases of active pulmonary TB. Policies that reduce HIV transmission among injection drug users and improve the nutritional status of socially isolated inmates may alleviate the TB burden in Tajikistan’s prisons. PMID:24465861

  15. CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between individuals with latent and active TB infection.

    PubMed

    Canaday, David H; Sridaran, Sankar; Van Epps, Puja; Aung, Htin; Burant, Christopher J; Nsereko, Mary; Mayanja-Kizza, Harriet; Betts, Michael R; Toossi, Zahra

    2015-07-01

    CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher than with other opportunistic infections suggesting that progression to PTB is not merely due to T cell depletion but also dysfunction. There are limited data examining T cell functional signatures in human HIV-TB co-infection particularly in PTB which accounts for about 80% of active TB disease overall. We examined a cohort of HIV-infected anti-retroviral naïve individuals in Kampala, Uganda, a TB endemic area using multiparametric flow cytometry analysis to determine IFN-γ, IL-2, IL-17, and TNF-α production in CD4+ memory T cell subsets. The cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a smoldering state of persistent MTB replication rather than dormant infection. This may be a contributory mechanism to the significantly increased risk of progression to PTB in this population.

  16. Pyrido[1,2-a]benzimidazole-based agents active against tuberculosis (TB), multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB.

    PubMed

    Pieroni, Marco; Tipparaju, Suresh K; Lun, Shichun; Song, Yang; Sturm, A Willem; Bishai, William R; Kozikowski, Alan P

    2011-02-07

    The struggle against tuberculosis (TB) is still far from over. TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. Co-infection with human immunodeficiency virus (HIV) and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. Herein, we report the discovery of 2-(4-chlorobenzyl)-3-methyl-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitrile as an effective antitubercular agent and the structural modifications of this molecule that have led to analogues with improved potency and lower toxicity. A number of these derivatives were also active at sub-micromolar concentrations against resistant TB strains and devoid of apparent toxicity to Vero cells, thereby underscoring their value as novel scaffolds for the development of new anti-TB drugs.

  17. Dotting the Three I's for collaborative TB-HIV activities: evaluation of a pilot programme in Kathmandu, Nepal.

    PubMed

    Sah, S K; Sahu, S K; Lamichhane, B; Bhatta, G K; Bhandari, K B; Owiti, P; Majumdar, S S

    2016-09-01

    Setting: The three government tertiary care hospitals providing care for people living with the human immunodeficiency virus (PLHIV) in Kathmandu, Nepal. Objectives: To assess 1) the screening cascades for intensified case finding for tuberculosis (TB), 2) isoniazid preventive therapy (IPT), including demographic and clinical factors associated with treatment interruption, and 3) TB infection control (IC) in the health facilities. Design: A cross-sectional study of new PLHIV enrolled from January 2012 to December 2014. Results: Among 572 registered PLHIV, 91% were on antiretroviral therapy. Of those registered, 561 (98%) were screened for TB and 73 (13%) were diagnosed with TB (17 [25%] sputum smear-positive, 17 [25%] smear-negative and 35 [51%] extra-pulmonary). Among the 488 (87%) PLHIV without active TB, 157 (32%) were initiated on IPT, of whom 136 (87%) completed treatment and 17 (11%) interrupted treatment. Those who experienced adverse events were 12 times more likely to interrupt IPT. TB IC showed gaps in personal control measures and supporting structures and policies. Conclusion: The implementation of the Three I's for collaborative TB-HIV activities in pilot sites in Nepal was successful and should be scaled up.

  18. Prevalence of tuberculosis, HIV, and TB-HIV co-infection among pulmonary tuberculosis suspects in a predominantly pastoralist area, northeast Ethiopia

    PubMed Central

    Belay, Mulugeta; Bjune, Gunnar; Abebe, Fekadu

    2015-01-01

    Background TB-HIV co-infection is one of the biggest public health challenges in sub-Saharan Africa. Although there is a wealth of information on TB-HIV co-infection among settled populations in Africa and elsewhere, to our knowledge, there are no published reports on TB-HIV co-infection from pastoral communities. In this study, we report the prevalence of TB, HIV and TB-HIV co-infection among pulmonary TB suspects in the Afar Regional State of Ethiopia. Design In a cross-sectional study design, 325 pulmonary TB suspects were included from five health facilities. Three sputum samples (spot-morning-spot) were collected from each participant. Sputum samples were examined for the presence of acid fast bacilli using Ziehl–Neelsen staining method, and culture was done on the remaining sputum samples. Participants were interviewed and HIV tested. Results Of the 325 pulmonary TB suspects, 44 (13.5%) were smear positive, and 105 (32.3%) were culture positive. Among smear-positive patients, five were culture negative and, therefore, a total of 110 (33.8%) suspects were bacteriologically confirmed pulmonary TB patients. Out of 287 pulmonary TB suspects who were tested for HIV infection, 82 (28.6%) were HIV positive. A significantly higher proportion of bacteriologically confirmed pulmonary TB patients [40 (40.4%)] were HIV co-infected compared with patients without bacteriological evidence for pulmonary TB [42 (22.3%)]. However, among ethnic Afar pastoralists, HIV infections in smear- and/or culture-negative pulmonary TB suspects [7 (7.6%)] and bacteriologically confirmed pulmonary TB patients [4 (11.8%)] were comparable. On multivariable logistic regression analysis, Afar ethnicity was independently associated with low HIV infection [OR=0.16 (95% CI: 0.07–0.37)], whereas literacy was independently associated with higher HIV infection [OR=2.21 (95% CI: 1.05–4.64)]. Conclusions Although the overall prevalence of TB-HIV co-infection in the current study is high, ethnic

  19. Determinants of active pulmonary tuberculosis in Ambo Hospital, West Ethiopia

    PubMed Central

    Mengiste, Bezatu; Mesfin, Frehiwot; Godana, Wanzahun

    2015-01-01

    Objectives The aim of this study was to determine factors associated with active pulmonary tuberculosis seen in cases in Ambo Hospital, Ethiopia. Design A facility-based prospective case-control study. Setting Patients attending Ambo Hospital from 01 December 2011 to 29 March 2012. Participants The sample included 312 adult patients attending Ambo Hospital. The main outcome measure was presence of active pulmonary tuberculosis (TB). Explanatory measures Age, gender, occupation, educational status, marital status, place of residence, patient history of TB, family history of TB, human immunodeficiency virus (HIV) infection, smoking, alcohol intake, khat chewing, body mass index (BMI), employment, diabetes, history of asthma, previous history of worm infestation, history of hospitalisation, number of adults living in the household (HH), person per room, housing condition. Results A total of 312 study participants, including 104 active pulmonary tuberculosis (PTB) cases (cases) and 208 non-active PTB cases (controls), were recruited for the present study. Having one or more family member with a history of TB (OR = 4.4; 95% CI: 1.50–12.90), marital status (OR = 7.6; 95% CI: 2.2–12.6), male gender (OR = 3.2; 95% CI: 1.4–7), rural residence (OR = 3.3; P = 0.012), being a current or past smoker (OR = 2.8; 95% CI: 1.1–7.2), BMI < 18.5 (OR = 2.1; 95% CI: 1.03–4.2), HIV infection (OR = 8.8; 95% CI: 2.4–23.8) and a history of worm infestation (OR = 6.4; 95% CI: 2.6–15.4) remained significant independent host-related factors for active PTB. Conclusion Patients who came from a compound with more than two HHs were more likely to develop active PTB than those who came from a compound with only one HH. Those who lived in houses with no windows were more likely to develop active PTB than those who lived in houses with one or more windows, had a family history of TB, lived in rural areas. Sex of the patient was a predicting factor. Not being the owner of the house was

  20. Diagnostic Values of the QuantiFERON-TB Gold In-Tube Assay Carried out in China for Diagnosing Pulmonary Tuberculosis

    PubMed Central

    Li, Fabin; Longuet, Christophe; Vernet, Guy; Goletti, Delia; Zhao, Yanlin; Lagrange, Philippe H.

    2015-01-01

    Background Interferon-release assays (IGRAs) for diagnosing active pulmonary tuberculosis (PTB) are not yet fully validated, particularly in high TB-endemic areas as the People's Republic of China (PRC). The aim of this report was to assess the performance of the QuantiFERON-TB Gold In-tube (QFT-GIT) and tuberculin skin test (TST), in addition to microbiological results, as contributors for diagnosing active PTB in the PRC. Methods/Principal Findings A total of 300 PTB patients, 41 disease controls (DC) and 59 healthy community controls (HCC) were included prospectively between May 2010 and April 2011 from two provinces of the PRC (Heilongjiang and Zhejiang). The QFT-GIT and TST yielded an overall sensitivity for active TB of 80.9% and 86.2%, and a specificity of 36.6% and 26.8%, respectively. The province of origin and smear microscopy status did not significantly impact the diagnostic values for PTB. However, using the TST with a 10 mm cut-off point, a significantly higher proportion of LTBI was observed in the DC than the HCC (p=0.01). Discordant results between the QFT-GIT and TST were found among 1/3 of the PTB, HCC and DC. Two-thirds of the individuals presented TST-positive/QFT-GIT-negative discordant results. The TST-negative/QFT-GIT-positive result was not associated with age or bacillary load. Cumulative QFT-GIT and TST positive results increased the overall sensitivity (95.9%), but it was associated with a dramatic decrease of the overall specificity (24.8%) leading to a suboptimal PPV (80.1%) and a low NPV (61.1%). Conclusions/Significance The usefulness of the QFT-GIT to diagnose active TB in high TB-endemic countries remains doubtful because like the TST, the QFT-GIT cannot distinguish between LTBI and active TB. Used as single stand-alone tests, both the QFT-GIT and TST have very limited roles in the diagnosis of active PTB. However, the combined use of SM, the TST and QFT-GIT may allow for the exclusion of ATB. PMID:25867946

  1. Effect of Active Case Finding on Prevalence and Transmission of Pulmonary Tuberculosis in Dhaka Central Jail, Bangladesh

    PubMed Central

    Banu, Sayera; Rahman, Md. Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md. Siddiqur Rahman; Rahman, Md. Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D.

    2015-01-01

    Background Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh

  2. Rapid detection of Mycobacterium tuberculosis in sputum by Patho-TB kit in comparison with direct microscopy and culture.

    PubMed

    Ben-Selma, Walid; Ben-Kahla, Imen; Marzouk, Manel; Ferjeni, Asma; Ghezal, Samira; Ben-Said, Moncef; Boukadida, Jalel

    2009-11-01

    The usefulness of a new rapid diagnostic test (Patho-TB) using antibodies specific to mycobacterial antigens was evaluated for the rapid discrimination between pulmonary tuberculosis (TB) and non-TB pulmonary diseases on sputa. One hundred sputa collected from 79 active TB patients and from 21 patients with non-TB pulmonary diseases (asthma and chronic obstructive pulmonary disease) were enrolled into the study and tested for the presence of Mycobacterium tuberculosis by Ziehl-Neelsen smear, Patho-TB kit, and Löwenstein-Jensen culture. The sensitivity, specificity, positive predictive value, and negative predictive value of the Patho-TB test were 95%, 100%, 100%, and 84%, respectively. Patho-TB test is simple, quick, and easy to perform. Its sensitivity, specificity, and positive predictive value are satisfactory. Therefore, it could be used as a screening test in poorly equipped laboratories of TB endemic areas.

  3. MCP-1 -2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients.

    PubMed

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-11-01

    Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) -2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 -2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26-2.66; OR = 3.1, 95% CI = 1.28-7.76; respectively]. However, wild type allele -2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, -2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35-0.89, Pc = 0.03). Our findings confirm the key role of -2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.

  4. ERK activation by thymosin-beta-4 (TB4) overexpression induces paclitaxel-resistance.

    PubMed

    Oh, Su-Young; Song, Ji-Hee; Gil, Jung-Eun; Kim, Jeong-Hee; Yeom, Young-Il; Moon, Eun-Yi

    2006-05-15

    The development of paclitaxel-resistance in tumors is one of the most significant obstacles to successful therapy. Thymosin-beta-4 (TB4) has been known as actin-sequestering protein and functions in tumor metastasis. Here, we overexpressed TB4 in HeLa cells (TB4-HeLa) and examined the effect of TB4 in paclitaxel-induced cell death. TB4-HeLa cells showed a higher growth rate and a lower percentage of basal apoptosis than HeLa cells. TB4-HeLa cells were more resistant to paclitaxel-induced cell death than HeLa cells. TB4 transcript expression with paclitaxel treatment was dose-dependently increased in HeLa cells but that was not in TB4-HeLa cells. Small interfering RNA (siRNA) of TB4 inhibited HeLa cell growth and enhanced paclitaxel-induced cell death. Basal ERK phosphorylation was elevated and basal p38 kinase phosphorylation was reduced in paclitaxel non-treated TB4-HeLa cells. When treated with paclitaxel, cell death and resistance-induction were independent of ERK and p38 kinase activation. Paclitaxel-resistance of TB4-HeLa cells was overcome by the inhibition of basal ERK activity with PD98059 pre-treatment. The inhibition of basal p38 kinase activity with SB203580 pre-treatment attenuated the paclitaxel-induced HeLa cell death. In conclusion, TB4 induced paclitaxel-resistance through the elevation of basal level of ERK phosphorylation. Therefore, TB4 could be a novel target to regulate paclitaxel-resistance.

  5. LTB4 activates pulmonary artery adventitial fibroblasts in pulmonary hypertension

    PubMed Central

    Jiang, Xinguo; Tamosiuniene, Rasa; Sung, Yon K.; Shuffle, Eric M.; Tu, Allen B.; Valenzuela, Antonia; Jiang, Shirley; Zamanian, Roham T.; Fiorentino, David F.; Voelkel, Norbert F.; Peters-Golden, Marc; Stenmark, Kurt R.; Chung, Lorinda; Rabinovitch, Marlene; Nicolls, Mark R.

    2015-01-01

    A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of the current study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast (HPAAF) proliferation, migration and differentiation in a dose-dependent manner through its cognate G-protein coupled receptor, BLT1. LTB4 activated HPAAF by up-regulating p38 MAPK as well as Nox4 signaling pathways. In an autoimmune model of PH, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation and attenuated PH development. This study uncovers a novel mechanism by which LTB4 further promotes PAH pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID:26558820

  6. IL23R(Arg381Gln) Functional Polymorphism Is Associated with Active Pulmonary Tuberculosis Severity

    PubMed Central

    Boukadida, Jalel

    2012-01-01

    The purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 Gwild type → Areduced function, Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that the IL23R reduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P = 10−8], 33% versus 5% [P = 10−8], and 36% versus 26% [P = 5 × 10−3], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P = 4 × 10−5) and 7.74-fold (P = 10−5) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in Tunisian patients. PMID:22695161

  7. Granulocytic Myeloid Derived Suppressor Cells Expansion during Active Pulmonary Tuberculosis Is Associated with High Nitric Oxide Plasma Level

    PubMed Central

    El Daker, Sary; Sacchi, Alessandra; Tempestilli, Massimo; Carducci, Claudia; Goletti, Delia; Vanini, Valentina; Colizzi, Vittorio; Lauria, Francesco Nicola; Martini, Federico; Martino, Angelo

    2015-01-01

    Tuberculosis (TB) is still the principal cause of death caused by a single infectious agent, and the balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. The aim of this work was to study the role of myeloid-derived suppressor cells (MDSCs) during active pulmonary tuberculosis at the site of infection. We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma. We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB. Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy. PMID:25879532

  8. Interferon gamma +874T/A polymorphism is associated with susceptibility to active pulmonary tuberculosis development in Tunisian patients.

    PubMed

    Ben Selma, Walid; Harizi, Hedi; Bougmiza, Iheb; Hannachi, Naila; Ben Kahla, Imen; Zaieni, Radhia; Boukadida, Jalel

    2011-06-01

    Interferon gamma (IFN-γ) is a key cytokine involved mainly in the defense against intracellular pathogens such as Mycobacterium tuberculosis. Given its key role in the control of tuberculosis (TB), in the present article we have investigated a possible association between IFN-γ gene single-nucleotide polymorphism linked to high and low producer phenotypes (IFN-γ [+874T(high) → A(low)]) (rs2430561) and risk development of active TB in Tunisian patients. Genomic DNA samples were obtained from 223 patients with active TB (168 pulmonary and 55 extrapulmonary cases) and 150 healthy blood donors. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism method. The +874 AA genotype (low IFN-γ producer) was significantly associated with increased risk of developing of active pulmonary TB (odds ratio [OR] = 2.18; 95% confidence intervals [CI], 1.33-3.57; P corrected for the number of genotypes [Pc] = 0.003). By contrast, the AT genotype was found to be significantly associated with resistance to pulmonary TB (OR = 0.46; 95% CI, 0.28-0.74; Pc = 0.0018) and extrapulmonary TB development (OR = 0.46; 95% CI, 0.23-0.91; Pc = 0.045). Collectively, our data showed that the IFN-γ +874T/A polymorphism is a determinant in the resistance or susceptibility to the development of active TB in the studied population.

  9. Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB).

    PubMed

    Dlugovitzky, D; Bay, M L; Rateni, L; Fiorenza, G; Vietti, L; Farroni, M A; Bottasso, O A

    2000-12-01

    Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-beta), nitric oxide and tumour necrosis factor-alpha (TNF-alpha) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-gamma), IL-4, IL-12, TGF-beta, TNF-alpha and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 +/- 13 years (mean +/- s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-gamma, TGF-beta and TNF-alpha production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-gamma were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-beta and TNF-alpha concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease.

  10. Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB)

    PubMed Central

    Dlugovitzky, D; Bay, M L; Rateni, L; Fiorenza, G; Vietti, L; Farroni, M A; Bottasso, O A

    2000-01-01

    Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-β), nitric oxide and tumour necrosis factor-alpha (TNF-α) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-γ), IL-4, IL-12, TGF-β, TNF-α and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 ± 13 years (mean ±s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-γ, TGF-β and TNF-α production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-γ were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-β and TNF-α concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease. PMID:11122239

  11. Anti-TB activity of Evodia elleryana bark extract

    PubMed Central

    Barrows, Louis R.; Powan, Emma; Pond, Christopher D.; Matainaho, Teatulohi

    2009-01-01

    An ethyl acetate extract of bark from Evodia elleryana produced significant growth inhibition of Mycobacterium tuberculosis at concentrations only minimally inhibitory to human T cells. The crude extract yielded 95% inhibition of TB at 50 μg/ml. The crude extract yielded 29 % growth inhibition of human T-cells in culture at that concentration. PMID:17350179

  12. miRNA Signatures in Sera of Patients with Active Pulmonary Tuberculosis

    PubMed Central

    Valente, Ilaria C.; Norbis, Luca; Sotgiu, Giovanni; Bosu, Roberta; Ambrosi, Alessandro; Codecasa, Luigi R.; Goletti, Delia; Matteelli, Alberto; Ntinginya, Elias N.; Aloi, Francesco; Heinrich, Norbert; Reither, Klaus; Cirillo, Daniela M.

    2013-01-01

    Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of “relevant miRNAs”, we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2–90.0), and 77% (CI 64.2–85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1–92.1), and 81% (65.0–90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4–99.1), and 100% (83.9–100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the

  13. CT findings of pulmonary tuberculosis and tuberculous pleurisy in diabetes mellitus patients

    PubMed Central

    Kim, Jihyun; Lee, In Jae; Kim, Joo-Hee

    2017-01-01

    PURPOSE We aimed to assess computed tomography (CT) findings of pulmonary tuberculosis (TB) and TB pleurisy in diabetes mellitus (DM) patients and to evaluate the effect of duration of DM on radiologic findings of pulmonary TB and TB pleurisy. METHODS Ninety-three consecutive patients diagnosed as active pulmonary TB with underlying DM were enrolled in our study. As a control group, 100 pulmonary TB patients without DM were randomly selected. TB patients with DM were subdivided into two subgroups depending on diabetes duration of ≥10 years or <10 years. Medical records and CT scans of the patients were retrospectively reviewed and compared. RESULTS Bilateral pulmonary involvement (odds ratio [OR]=2.39, P = 0.003), involvement of all lobes (OR=2.79, P = 0.013), and lymph node enlargement (OR=1.98, P = 0.022) were significantly more frequent CT findings among TB patients with DM compared with the controls. There were no statistically significant differences in CT findings of pulmonary TB depending on the duration of DM. CONCLUSION Bilateral pulmonary involvement, involvement of all lobes, and lymph node enlargement are significantly more common CT findings in TB patients with underlying DM than in patients without DM. Familiarity with the CT findings may be helpful to suggest prompt diagnosis of pulmonary TB in DM patients. PMID:28185999

  14. IL23R(Arg381Gln) functional polymorphism is associated with active pulmonary tuberculosis severity.

    PubMed

    Ben-Selma, Walid; Boukadida, Jalel

    2012-08-01

    The purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 G(wild type) → A(reduced function), Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that the IL23R reduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P = 10(-8)], 33% versus 5% [P = 10(-8)], and 36% versus 26% [P = 5 × 10(-3)], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P = 4 × 10(-5)) and 7.74-fold (P = 10(-5)) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in Tunisian patients.

  15. Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV Patients with Culture Confirmed Pulmonary Tuberculosis in India and the Potential Role of IL-6 in Prediction

    PubMed Central

    Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya

    2013-01-01

    Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062

  16. Factors Related to Non-Referral of Patients with Presumptive Pulmonary TB to Designated Microscopy Centers (DMCs) by Registered Private Practitioners in Urban Areas of Punjab, India

    PubMed Central

    Sharma, Shruti; Whig, Jagdeep; Satija, Mahesh; Chaudhary, Anurag

    2015-01-01

    Background Early diagnosis and proper treatment under RNTCP guidelines, forms the mainstay of management of a TB patient. A large proportion of patients with presumptive tuberculosis (TB) visit a Private Practitioner (PP) in the first place. Studies have shown that PPs rely more on X-rays and other diagnostic tools rather than referring the patient to the nearest Designated Microscopy Centre (DMC) for sputum microscopy. Aim The present study was planned to look in to factors responsible for non-referral of patients with presumptive pulmonary TB to the DMCs for diagnosis by PPs. Materials and Methods Present study was a case-control study conducted over a period of one year among registered PPs in urban areas of Punjab. The study was carried out in five major cities which have approximately half of the urban population of Punjab. Forty three Private Practitioners per city for referral group and 43 matched PPs for non-referral group were selected. Results Knowledge regarding RNTCP was low in both the referral (38.1%) as well as non-referral (25.6%) group of PPs. Allopathic doctors had significantly higher knowledge regarding TB as compared to ayurvedic and homeopathy doctors, and Registered Medical Practitioners (RMP). Both the knowledge of PPs regarding nearest DMC as well as perception about accessibility of the nearest DMC for the patients were found to be significantly higher in the referral group. Only 15.3% of practitioners in the non-referral group said that they had been contacted by RNTCP staff. Conclusion The main factors responsible for non-referral of pulmonary TB suspects to DMCs for diagnosis in the present study included low knowledge regarding RNTCP, lack of awareness regarding place and accessibility of nearest DMC, and inadequate sensitization of PPs by the RNTCP staff. PMID:26674553

  17. Serial T-SPOT.TB and quantiFERON-TB-Gold In-Tube assays to monitor response to antitubercular treatment in Italian children with active or latent tuberculosis infection.

    PubMed

    Chiappini, Elena; Bonsignori, Francesca; Mangone, Giusi; Galli, Luisa; Mazzantini, Rachele; Sollai, Sara; Azzari, Chiara; de Martino, Maurizio

    2012-09-01

    We performed a prospective study to investigate T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-G-IT) dynamics during antitubercular treatment in active tuberculosis (TB) or latent TB. Eighteen children with latent TB and 26 with TB were enrolled. At 6 months of follow-up reversion rate was 5.88% (95% CI:0-13.79) for QFT-G-IT; 9.09% (95% CI:0.59-17.58) for T-SPOT.TB (P=0.921) in TB cases. Significant decline in quantitative response was observed exclusively in TB cases. Our results suggest that serial IGRA have limited use in children receiving antitubercular treatment.

  18. Tomographic Aspects of Advanced Active Pulmonary Tuberculosis and Evaluation of Sequelae following Treatment

    PubMed Central

    Capone, Domenico; Mafort, Thiago; Mogami, Roberto; Rodrigues, Rosana de Souza; Menna Barreto, Miriam

    2017-01-01

    Objectives. To evaluate tomographic changes in pulmonary tuberculosis (TB), degree of agreement among three radiologists regarding tomographic diagnoses, and sequelae following treatment. Methods. Cross-sectional and descriptive study of 74 TB patients confirmed by sputum culture and chest computed tomography before (CT1) and 6 months after (CT2) drug therapy. Results were performed by three radiologists blinded to clinical and laboratory results. Results. Main findings in CT1 included nodules indicating the presence of a tree-in-bud pattern in 93% of cases, ill-defined nodules in 84% of cases, consolidation in 77% of cases, architectural distortion in 71% of cases, cavitary lesions in 62% of cases, and ground glass opacities in 37% of cases. Airway involvement, characterized by increased thickness and dilatation of the bronchial walls, occurred in 93% of cases. Pleural involvement occurred in 54%. There was an agreement on active TB among the three radiologists in 85% of cases. The results in CT2 indicated the presence of architectural distortion in 91% of cases and cylindrical bronchiectasis in 86%. Conclusions. The study established a tomographic pattern for diagnosis of active TB characterized by the presence of airway nodules, consolidation, architectural distortion, and cavitary lesions, and an almost complete degree of agreement (Kappa) was observed among the radiologists (0.85). CT after treatment assists in defining the cure. PMID:28261498

  19. The effect of green tea extract supplementation on sputum smear conversion and weight changes in pulmonary TB patients: A randomized controlled trial

    PubMed Central

    Honarvar, Mohammad Reza; Eghtesadi, Shahryar; Gill, Pooria; Jazayeri, Shima; Vakili, Mohammad Ali; Shamsardekani, Mohammad Reza; Abbasi, Abdollah

    2016-01-01

    Background: Acceleration in sputum smear conversion helps faster improvement and decreased probability of the transfer of TB. In this study, we aimed to investigate the effect of green tea extract supplementation on sputum smear conversion and weight changes in smear positive pulmonary TB patients in Iran. Methods: In this double blind clinical study, TB patients were divided into intervention, (n=43) receiving 500 mg green tea extract (GTE), and control groups (n=40) receiving placebo for two months, using balanced randomization. Random allocation and allocation concealment were observed. Height and weight were measured at the beginning, and two and six months post-treatment. Evaluations were performed on three slides, using the ZiehlNeelsen method. Independent and paired t test, McNemar’s, Wilcoxon, Kaplan-Meier, Cox regression model and Log-Rank test were utilized. Statistical significance was set at p<0.05. This trial was registered under IRCT201212232602N11. Results: The interventional changes and the interactive effect of intervention on weight were not significant (p>0.05). In terms of shortening the duration of conversion, the case to control proportion showed a significant difference (p=0.032). Based on the Cox regression model, the hazard ratio of the relative risk of delay in sputum smear conversion was 3.7 (p=0.002) in the higher microbial load group compared to the placebo group and 0.54 (95% CI: 0.31-0.94) in the intervention compared to the placebo group. Conclusion: GTE decreases the risk of delay in sputum smear conversion, but has no effect on weight gain. Moreover, it may be used as an adjuvant therapy for faster rehabilitation for pulmonary TB patients. PMID:27493925

  20. [Spontaneous pneumothorax associated to active pulmonary tuberculosis].

    PubMed

    Díaz Rojas, F; Córdova Gutiérrez, H; Aguirre Gas, H

    1978-01-01

    This paper reviewed 8 cases of spontaneous pneumothorax, associated to pulmonary tuberculosis during a period of time of two years at the A.L.M. General Hospital of Toluca, Mex. The diagnosis was confirmed by clinical picture, radiology and bacteriology studies. Six males and two females proceding of the low class; farmers all of them. Their age ranged between 18 and 35 years. Two of the patients showed cavitary lesions, five had difusse fibrosis of the lung. We analized the clinical manifestations and reviewed the pathogenic mechanisms as well the medical and surgical treatment. No deaths ocurred en this series. We concluded that the direct relation between active pulmonary tuberculosis and spontaneous pneumothorax is not clear, but their association in this serie suggested further studies to stablished this. We emphasized the importance of this complication rare in the world literature.

  1. TB Terms

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  2. Augmented photocatalytic activity and luminescence response of Tb³⁺ doped nanoscale titania systems

    SciTech Connect

    Paul, Nibedita; Deka, Amrita; Mohanta, Dambarudhar

    2014-10-14

    The present work reports on the effect of Tb³⁺ doping on the luminescence and photocatalytic performance of nano-structured titania derived through a sol-gel route. X-ray diffraction patterns have revealed the existence of anatase phase with and without Tb³⁺ doping and with an improved orientation factor along (004) and (200) planes. Transmission electron microscopy and selective area electron diffraction studies, while exhibiting ample poly-crystallinity feature, have predicted an average particle size of ~9 nm and ~6 nm for the un-doped and 5% Tb³⁺ doped nano-titania samples; respectively. Apart from emissions accompanied by different types of defects, Tb³⁺ related transitions, such as, ⁵D₃ → ⁷F₅, ⁵D₃ → ⁷F₄, and ⁵D₄ → ⁷F₆ were identified in the photoluminescence spectra. Brunauer-Emmett-Teller surface area analysis, as carried out on a Tb³⁺ doped nano-titania system, has demonstrated a more-open hysteretic loop owing to significant difference of N₂ adsorption/desorption rates. The photocatalytic activity of nano-titania, as evaluated from the nature of degradation of methyl orange under UV illumination, exhibited the highest efficiency for a Tb³⁺ doping level of 2.5%. The augmented photocatalytic degradation has also been discussed in the light of a model based on pseudo first-order kinetics.

  3. Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age

    PubMed Central

    Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

    2016-01-01

    Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30–49 years, 86.5% and 94.7%; 50–69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age. PMID:27258377

  4. Immunosuppression of pulmonary natural killer activity by exposure to ozone

    SciTech Connect

    Burleson, G.R.; Keyes, L.L.; Stutzman, J.D. )

    1989-01-01

    Ozone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a consequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring natural killer (NK) activity from whole-lung homogenates of male Fischer-344 rats. Results of this study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. The suppressed pulmonary NK response was thus attenuated and returned to normal values in the continued presence of ozone gas. This attenuation process is dynamic, complex, and doubtless involves several cell types and/or products of these cells. Pulmonary NK activity was also suppressed at 0.5 ppm ozone, but not at 0.1 ppm ozone, following 23.5 hours of exposure. NK activity is important for defense against viral, bacterial, and neoplastic disease. The depressed NK activity resulting from continuous ozone exposure could therefore result in a compromised ability to defend against pulmonary diseases.

  5. Predictive Role of ADA in Bronchoalveolar Lavage Fluid in Making the Diagnosis of Pulmonary Tuberculosis.

    PubMed

    Binesh, Fariba; Halvani, Abolhassan

    2013-01-01

    Current diagnostic tests for tuberculosis (TB) are time-consuming. The aim of this study was to evaluate the diagnostic usefulness of ADA in bronchoalveolar lavage fluid in patients with pulmonary TB. A cross-sectional study was performed in Yazd, Iran, between 2009 and 2010. Patients suspected of pulmonary TB with negative sputum smear for AFB were included in the study. Mean ADA levels in BAL fluids were measured and compared between study groups. Sixty-three patients were enrolled in the study among which 15 cases had pulmonary TB, 33 had pulmonary diseases other than TB, and 15 subjects with normal bronchoscopy results were considered as controls. Mean ADA levels in BAL fluid were 4.13 ± 2.55, 2.42 ± 1.06, and 1.93 ± 0.88, respectively. This rate was significantly higher in the pulmonary TB group compared to the other two groups (P = 0.001). Using ROC curve with a cut-off value of 3.5 IU/L, the highest sensitivity (57%) and specificity (84%) were obtained in diagnosis of TB. The results showed that although ADA activity in BAL fluid of pulmonary TB patients was higher than those seen in other diseases, a negative test does not rule out pulmonary TB.

  6. Rate of tuberculosis infection in children and adolescents with household contact with adults with active pulmonary tuberculosis as assessed by tuberculin skin test and interferon-gamma release assays.

    PubMed

    Ferrarini, M A G; Spina, F G; Weckx, L Y; Lederman, H M; De Moraes-Pinto, M I

    2016-03-01

    Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT.TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69·5% and 9·5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57·6% by T-SPOT.TB, and 59·3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83·1% and 92·8% in the exposed and control groups, respectively. In the exposed group, T-SPOT.TB added four TB diagnoses [16%, 95% confidence interval (CI) 1·6-30·4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24·7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6·9; >60 days: OR 27·0] and sleeping in the same room as an adult with active TB (OR 5·2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI.

  7. miR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation.

    PubMed

    Luo, Ying; Dong, Hai-Ying; Zhang, Bo; Feng, Zhao; Liu, Yi; Gao, Yu-Qi; Dong, Ming-Qing; Li, Zhi-Chao

    2015-02-01

    Activation of pulmonary adventitial fibroblasts plays a key role in the pulmonary vascular remodeling in hypoxic pulmonary hypertension. Previous studies showed that miRNAs participated in the regulation of fibroblast activation. This study explored the role of miR-29 in the activation of pulmonary adventitial fibroblasts and the therapeutic potential in hypoxic pulmonary hypertension. We found that hypoxia-induced pulmonary adventitial fibroblasts activation was accompanied with a drastic decrease of miR-29a-3p expression. Knockdown of hypoxia-inducible factor-1 α or Smad3 reversed the hypoxia-induced decrease of miR-29-3p in cultured pulmonary adventitial fibroblasts. In vitro, miR-29a-3p mimic inhibited the hypoxia-induced proliferation, migration, and secretion of pulmonary adventitial fibroblasts, suppressed the hypoxia-induced expression of α-smooth muscle actin and extracellular matrix collagen in pulmonary adventitial fibroblasts; however, miR-29a-3p inhibitor mimicked the effect of hypoxia on the activation of pulmonary adventitial fibroblasts. Further studies revealed that preventative or therapeutic administration of miR-29a-3p significantly decreased pulmonary artery pressure and right ventricle hypertrophy index and ameliorated pulmonary vascular remodeling in hypoxic pulmonary hypertension rats. These findings suggest that miR-29a-3p regulates the activation and phenotype of pulmonary adventitial fibroblasts in hypoxia and has preventative and therapeutic potential in hypoxic pulmonary hypertension.

  8. Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

    PubMed Central

    Tsenova, Liana; O'Brien, Paul; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Subbian, Selvakumar

    2014-01-01

    Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB. PMID:24831609

  9. Tuberculosis (TB)

    MedlinePlus

    ... with facebook share with twitter share with linkedin Tuberculosis (TB) Tuberculosis (TB) is a contagious and often ... are drug resistant. Why Is the Study of Tuberculosis (TB) a Priority for NIAID? Tuberculosis is one ...

  10. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens.

    PubMed

    Sali, Michela; De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Delogu, Giovanni; Giagulli, Cinzia

    2016-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance.

  11. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens

    PubMed Central

    De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Giagulli, Cinzia

    2015-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance. PMID:26491178

  12. Mass spectrometry imaging of levofloxacin distribution in TB-infected pulmonary lesions by MALDI-MSI and continuous liquid microjunction surface sampling.

    PubMed

    Prideaux, Brendan; ElNaggar, Mariam S; Zimmerman, Matthew; Wiseman, Justin M; Li, Xiaohua; Dartois, Véronique

    2015-02-01

    A multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and a commercial liquid microjunction surface sampling technology (LMJ-SSP), or flowprobe, have been used to both spatially profile and image drug distributions in lung tissue sections from TB-infected rabbits following oral administration of a single human-equivalent dose. Levofloxacin levels were highest at 6 h post-dose in normal lung, cellular granuloma, and necrotic caseum compartments. The drug accumulated in the cellular granuloma regions with lower amounts partitioning into central caseous compartments. Flowprobe imaging at 630 μm (limited by the probe tip diameter) enabled visualization of drug distribution into lesion compartments, including limited differentiation of relative drug abundance in cellular versus caseous regions of the lesions. MALDI-MSI analysis at 75 μm provided more detailed drug distribution, which clearly accumulated in the cellular region immediately surrounding the central caseum core. Imaging and profiling data acquired by flowprobe and MALDI-MSI were validated by quantitative LC/MS/MS analysis of lung and granuloma homogenates taken from the same animals. The results of the investigation show flowprobe imaging and sampling as a rapid and sensitive alternative to MALDI-MSI for profiling drug distributions into tissues when spatial resolution of data below the threshold of the probe diameter is not required.

  13. First Outcome of MDR-TB among Co-Infected HIV/TB Patients from South-West Iran

    PubMed Central

    Motamedifar, Mohammad; Abadi, Ali Reza Hassan; Moghadam, Mahboube Nakhzari

    2015-01-01

    Background Tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV) patients and the majority of them occur in developing countries. The aims of the present study were to determine the frequency of HIV/TB co-infection and other probable associated factors. Methods This 10 year retrospective study was conducted on 824 HIV patients in the south-west of Iran. HIV infection was diagnosed by the enzyme linked immunosorbent assay and confirmed by Western blot. TB diagnosis was based on consistency of the clinical manifestations, chest X-ray, and microscopic examination. Drug susceptibility testing was done by the proportional method on Löwenstein-Jensen media. Results Of 824 HIV patients, 59 (7.2%) were identified as TB co-infected and the majority (86.4%) of them were male. Of the overall TB infected patients, 6 cases (10.2%) showed multidrug-resistant with the mean CD4+ lymphocyte count of 163±166 cells/mm3. The main clinical forms of TB were pulmonary (73%). There was a significant (p<0.05) correlation between TB infection and CD4+ lymphocyte counts ≤200 cells/mm3, gender, prison history, addiction history, and highly active anti-retroviral therapy. Conclusion We reported novel information on frequency of HIV/TB co-infection and multidrug resistant-TB outcome among co-infected patients that could facilitate better management of such infections on a global scale. PMID:26175780

  14. Long lasting phosphorescence and photostimulated luminescence in Tb-ion-activated reduced calcium aluminate glasses

    NASA Astrophysics Data System (ADS)

    Kinoshita, Takeru; Yamazaki, Masaaki; Kawazoe, Hiroshi; Hosono, Hideo

    1999-10-01

    Long lasting phosphorescence (LLP) and photostimulated luminescence (PSL) were found in reduced calcium aluminate glasses activated with Tb3+ ions. The LLP from Tb3+ was observed by illuminating the Tb3+ 4f→5d charge transfer band with ultraviolet (UV) 254 nm light, while the PSL was seen by stimulating the UV-illuminated glasses with 633 nm light. The decay curve of the LLP was fitted with a second-order kinetic for the initial period (030 min). An electron paramagnetic resonance (EPR) signal, which is attributed to an F+-like center associated with Ca2+ ions, was induced by illumination with UV light and its intensity decay was fitted with a first-order kinetic similarly to the later stage of the LLP. The appearance of the PSL by illumination is accompanied by a distinct intensity reduction of the EPR signal due to the F+-like center. The thermoluminescence spectra of the specimen illuminated with UV light at 77 K consist of two components peaking at ˜240 and ˜390 K. The low temperature component and the high temperature component were attributed to an F-like center and an F+-like center, respectively. These results lead to a conclusion that electrons of the F-like center and the F+-like center contribute predominantly to the emergence of the LLP and the PSL, respectively.

  15. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB

    PubMed Central

    Barr, David A.; Kamdolozi, Mercy; Nishihara, Yo; Ndhlovu, Victor; Khonga, Margaret; Davies, Geraint R.; Sloan, Derek J.

    2016-01-01

    Summary Faster elimination of drug tolerant ‘persister’ bacteria may shorten treatment of tuberculosis (TB) but no method exists to quantify persisters in clinical samples. We used automated image analysis to assess whether studying growth characteristics of individual Mycobacterium tuberculosis colonies from sputum on solid media during early TB treatment facilitates ‘persister’ phenotyping. As Time to Detection (TTD) in liquid culture inversely correlates with total bacterial load we also evaluated the relationship between individual colony growth parameters and TTD. Sputum from TB patients in Malawi was prepared for solid and liquid culture after 0, 2 and 4 weeks of treatment. Serial photography of agar plates was used to measure time to appearance (lag time) and radial growth rate for each colony. Mixed-effects modelling was used to analyse changing growth characteristics from serial samples. 20 patients had colony measurements recorded at ≥1 time-point. Overall lag time increased by 6.5 days between baseline and two weeks (p = 0.0001). Total colony count/ml showed typical biphasic elimination, but long lag time colonies (>20days) had slower, monophasic decline. TTD was associated with minimum lag time (time to appearance of first colony1). Slower elimination of long lag time colonies suggests that these may represent a persister subpopulation of bacilli. PMID:27156626

  16. Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting

    PubMed Central

    Sharma, Surendra K.; Vashishtha, Richa; Chauhan, L. S.; Sreenivas, V.; Seth, Divya

    2017-01-01

    Background There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings. Methods 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases. Results Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72–1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97–2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients. Conclusion Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings. PMID:28060926

  17. Immunosuppression of pulmonary natural killer activity by exposure to ozone

    SciTech Connect

    Burleson, G.R.; Keyes, L.L.; Stutzman, J.D.

    1989-01-01

    Ozone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a subsequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring NK activity from whole-lung homogenate of male Fischer-344 rats. Results of the study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. This adaption, or attenuation process, is complex and poorly understood. Pulmonary NK activity was also suppressed at 0.5 ppm ozone, but not at 0.1 ppm ozone, for 23.5 hours. NK activity is important for defense against viral, bacterial, and neoplastic disease.

  18. Functional profile of CD4+ and CD8+ T cells in latently infected individuals and patients with active TB.

    PubMed

    Marín, Nancy D; París, Sara C; Rojas, Mauricio; García, Luis F

    2013-03-01

    Tuberculosis (TB) is one of the most important infectious diseases around the world. Several studies have focused on the identification of correlates of protection against TB. Most of them have concentrated on the study of IFN-γ due to its robust association with protection against TB. However, given the complexity of the immune response elicited after Mtb infection, other cytokines should also be considered. In the present study, we evaluated Th1 and Th17 responses and their association with the protection or development of active disease. Therefore, non infected individuals (nonTBi), latently infected individuals (LTBi) and patients with active TB (ATB) were studied. The evaluation of the number of cytokine producing cells by ELISPOT showed a higher number of IFN-γ-producing cells in ATB patients, but no differences were found regarding the number of IL-17 producing cells among studied groups. The evaluation of IFN-γ, IL-2, TNF-α and IL-17 producing CD4+ and CD8+ T cells at 1 day and 6 days of stimulation with mycobacterial antigens suggests the presence of functional signatures associated with latency or active TB. The results presented herein suggest the possible use of the evaluation of Th1-type cytokines, such as IFN-γ and/or TNF-α, as a correlate of protection against TB; however, these results need to be validated for other groups.

  19. Active Referral: An Innovative Approach to Engaging Traditional Healthcare Providers in TB Control in Burkina Faso

    PubMed Central

    Kaboru, Berthollet Bwira

    2013-01-01

    Background and objective: The involvement of traditional healthcare providers (THPs) has been suggested among strategies to increase tuberculosis case detection. Burkina Faso has embarked on such an attempt. This study is a preliminary assessment of that model. Methods: Qualitative data were collected using unstructured key informant interviews with policy makers, group interviews with THPs and health workers, and field visits to THPs. Quantitative data were collected from program reports and the national tuberculosis (TB) control database. Results and analysis: The distribution of tasks among THPs, intermediary organizations and clinicians is appealing, especially the focus on active referral. THPs are offered incentives based on numbers of suspected cases confirmed by health workers at the clinic, based on microscopy results or clinical assessment. The positivity rate was 23% and 9% for 2006 and 2007, respectively. The contribution of the program to national case detection was estimated at 2% for 2006. Because it relied totally on donor funding, the program suffered from irregular disbursements, resulting in periodic decreases in activities and outcomes. Conclusions: The study shows that single interventions require a broader positive policy environment to be sustainable. Even if the active referral approach seems effective in enhancing TB case detection, more complex policy work and direction, domestic financial contribution and additional evidence for cost-effectiveness are needed before the approach can be established as a national policy. PMID:24359717

  20. Accuracy of QuantiFERON-TB Gold Test for Tuberculosis Diagnosis in Children

    PubMed Central

    Sali, Michela; Buonsenso, Danilo; Goletti, Delia; D’Alfonso, Pamela; Zumbo, Antonella; Fadda, Giovanni; Sanguinetti, Maurizio; Delogu, Giovanni; Valentini, Piero

    2015-01-01

    Objectives To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in children with suspected active or latent TB infection (LTBI). Methods A retrospective study was conducted on 621 children (0–14 years old) evaluated for TB infection or disease. Following clinical assessment, children were tested with the QFT-IT assay. Results Among the 140 active TB suspects, we identified 19 cases of active disease. The overall sensitivity for active TB was 87.5%, ranging from 62.5% in children 25–36 months old to 100% in children older than 49 months. The overall specificity for active TB was 93.6%. Among the 481 children tested for LTBI screening, 38 scored positive and all but 2 had at least one risk factor for TB infection. Among the 26 children with indeterminate results, bacterial, viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB related extra-pulmonary infections in 12 (46.1%). Conclusions Our results indicate that the children's response to QFT-IT associates to active TB and risk factors for LTBI. Moreover, we show that mitogen response is also found in children of 1 year of age, providing support for QFT-IT use also in young children. PMID:26439935

  1. Adult pulmonary tuberculosis as a pathological manifestation of hyperactive antimycobacterial immune response.

    PubMed

    Kumar, Pawan

    2016-12-01

    The intricate relationship between tuberculosis (TB) and immune system remains poorly understood. It is generally believed that weakening of the immune response against Mycobacterium tuberculosis leads to reactivation of latent infection into the active pulmonary disease. However, heterogeneous nature of TB and failure of rationally designed vaccines in clinical trials raises serious questions against the simplistic view of TB as an outcome of weakened immunity. In the wake of accumulating human TB data, it is argued here that a hyperactive antimycobacterial immune response is to blame for the pathogenesis of pulmonary TB in immunocompetent adults. Direct and indirect evidence supporting this notion is presented in this article. Revisiting the role of immune system in TB pathogenesis will pave the way for effective anti-TB vaccines.

  2. Pulmonary Rehabilitation and Physical Activity in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Spruit, Martijn A; Pitta, Fabio; McAuley, Edward; ZuWallack, Richard L; Nici, Linda

    2015-10-15

    Physical inactivity is common in patients with chronic obstructive pulmonary disease (COPD) compared with age-matched healthy individuals or patients with other chronic diseases. Physical inactivity independently predicts poor outcomes across several aspects of this disease, but it is (at least in principle) treatable in patients with COPD. Pulmonary rehabilitation has arguably the greatest positive effect of any current therapy on exercise capacity in COPD; as such, gains in this area should facilitate increases in physical activity. Furthermore, because pulmonary rehabilitation also emphasizes behavior change through collaborative self-management, it may aid in the translation of increased exercise capacity to greater participation in activities involving physical activity. Both increased exercise capacity and adaptive behavior change are necessary to achieve significant and lasting increases in physical activity in patients with COPD. Unfortunately, it is readily assumed that this translation occurs naturally. This concise clinical review will focus on the effects of a comprehensive pulmonary rehabilitation program on physical activity in patients with COPD. Changing physical activity behavior in patients with COPD needs an interdisciplinary approach, bringing together respiratory medicine, rehabilitation sciences, social sciences, and behavioral sciences.

  3. Immune Activation at Sites of HIV/TB Co-Infection Contributes to the Pathogenesis of HIV-1 Disease

    PubMed Central

    Meng, Qinglai; Sayin, Ismail; Canaday, David H.; Mayanja-Kizza, Harriet; Baseke, Joy; Toossi, Zahra

    2016-01-01

    Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed. The T cell phenotype and activation status of HIV-1 p24 + T cells in PFMC and PBMC from HIV/TB patients were determined. We found that T cell and macrophage-specific and non-specific soluble markers of immune activation, sCD27, sCD163, IL1Ra, and sCD14, were higher in pleural fluid as compared to plasma from HIV/TB co-infected subjects, and higher as compared to pleural fluid from TB mono-infected subjects. Intestinal fatty acid-binding protein, a marker of intestinal tract damage, in plasma from HIV/TB co-infected patients was not different than that in HIV+ subjects. Expression of HLADR and CD38 double positive (HLADR/CD38) on CD4 T cells, and CD69+ on CD8 T cells correlated with pleural fluid viral load, and inversely with blood CD4 T cell count. Higher expression of HLADR/CD38 and CCR5 on CD4 T cells, and HLADR/CD38 and CD69 on CD8 T cells in PFMC were limited to effector memory populations. HIV-1 p24+ CD8 negative (includes CD4 + and double negative T cells) effector memory T cells in PFMC had higher expression of HLADR/CD38, Ki67, and CCR5 compared to HIV-1 p24- CD8 negative PFMC. Cumulatively, these data indicate that sites of HIV/TB co-infection are the source of intense immune activation. PMID:27870882

  4. BTLA exhibits immune memory for αβ T cells in patients with active pulmonary tuberculosis

    PubMed Central

    Zeng, Jin-Cheng; Lin, Dong-Zi; Yi, Lai-Long; Liu, Gan-Bin; Zhang, Hui; Wang, Wan-Dang; Zhang, Jun-Ai; Wu, Xian-Jing; Xiang, Wen-Yu; Kong, Bin; Chen, Zheng W; Wang, Cong-Yi; Xu, Jun-Fa

    2014-01-01

    Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in αβ T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on αβ T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for αβ T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-γ and perforin, which are important for immune memory against TB infection. BTLAhigh αβ T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on αβ T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection. PMID:25360214

  5. Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

    PubMed

    Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

    2016-10-01

    The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy.

  6. Solgel-hydrothermal synthesis of Tb/Tourmaline/TiO2 nano tubes and enhanced photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Huang, Fengping; Guo, Yuyu; Wang, Shuai; Zhang, Shuang; Cui, Mengli

    2017-02-01

    In this study, we synthesized Tb/Tourmaline/TiO2 nano tubes (NTs) through a solgel-hydrothermal method. The as-prepared samples were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectromicroscope, scanning electron microscopy, transmission electron microscopy and UV-vis diffuse reflectance spectroscopy. The resulting Tb/Tourmaline/TiO2 NTs exhibited higher photocatalytic activity than pure TiO2 and TiO2 nano particles (NPs) in the degradation of menthyl orange under UV-light. Results revealed that doping rare earth element Tb could narrow the wide band gap of TiO2 and tourmaline could trap the photogenerated electron of TiO2 to inhibit the recombination of photogenerated electron-hole pairs.

  7. Detection of pulmonary amylase activity in exhaled breath condensate.

    PubMed

    Zweifel, M; Rechsteiner, T; Hofer, M; Boehler, A

    2013-12-01

    Amylase activity in exhaled breath condensate (EBC) is usually interpreted as an indication of oropharyngeal contamination despite the fact that amylase can be found in pulmonary excretions. The aim of this study was to recruit and refine an amylase assay in order to detect amylase activity in any EBC sample and to develop a method to identify EBC samples containing amylase of pulmonary origin. EBC was collected from 40 volunteers with an EcoScreen condenser. Amylase assays and methods to discriminate between oropharyngeal and pulmonary proteins were tested and developed using matched EBC and saliva samples. Our refined 2-chloro-4-nitrophenyl-α-D-maltotriosid (CNP-G3) assay was 40-fold more sensitive than the most sensitive commercial assay and allowed detection of amylase activity in 30 µl of EBC. We developed a dot-blot assay which allowed detection of salivary protein in saliva diluted up to 150 000-fold. By plotting amylase activity against staining intensity we identified a few EBC samples with high amylase activity which were aligned with diluted saliva. We believe that EBC samples aligned with diluted saliva contain amylase activity introduced during EBC collection and that all other EBC samples contain amylase activity of pulmonary origin and are basically free of oropharyngeal protein contamination.

  8. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    SciTech Connect

    Cohen, G.M. )

    1990-04-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity.

  9. HIV-associated pulmonary tuberculosis.

    PubMed

    Nunn, P

    1991-11-01

    The problems of diagnosis, treatment and management of tuberculosis associated with HIV infection in Africa are placed in perspective by the former director of the Kenya Medical Research Institute. Tuberculosis (TB) has increased as much as 3-fold in many African countries due to heightened susceptibility of HIV patients. HIV infection may both re-activate latent TB, which virtually all Africans harbor, or increase the likelihood of exogenous infection or re-infection by TB. In most of Africa diagnosis by stained sputum smear is standard: in late AIDS, this method may yield false negatives due to non-pulmonary TB, or pulmonary TB with a negative smear. Chest x-rays are also atypical, since cavitation of the upper zones is not as common, but lobar consolidation and lower zone involvement, and various unusual findings are likely. There is no evidence that mycobacterium avium intracellular has occurred in Africa. Treatment in Africa often centers on long-term thiazina (thiacetazone and isoniazid combined). HIV+ patients are more prone to skin rashes or even lethal epidermal neurolysis as a complication of treatment. Treated patients should be monitored for other symptoms such as diarrhea, recurrent fevers, other chest infections, cerebral space occupying lesions, urinary infections. Many can be treated with broad spectrum antibiotics such as chloramphenicol. Nursing HIV-infected young adults is an expensive and burdensome prospect for overworked and underpaid staff, but curing TB in AIDS patients is possible and worthwhile because of the public health advantages.

  10. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis

    PubMed Central

    Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris‑Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian

    2016-01-01

    BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR

  11. Electrocatalysis of carbon black- or poly(diallyldimethylammonium chloride)-functionalized activated carbon nanotubes-supported Pd-Tb towards methanol oxidation in alkaline media

    NASA Astrophysics Data System (ADS)

    Wang, Li; Wang, Yi; Li, An; Yang, Yunshang; Tang, Qinghu; Cao, Hongbin; Qi, Tao; Li, Changming

    2014-07-01

    The Pd-Tb/C catalysts with different Pd/Tb ratios were synthesized by a simple simultaneous reduction reaction with sodium borohydride in aqueous solution. The structure and morphology of those catalysts had been characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The electrocatalytic performance of those catalysts for methanol oxidation in alkaline media was investigated using cyclic voltammetry (CV), linear sweep voltammetry (LSV) and CO stripping experiments. It is found that the 20%Pd-1%Tb/C catalyst has a higher catalytic activity than the 20%Pd/C catalyst, but the effect of Tb cannot be explained by a bi-functional mechanism. According to the X-Ray photoelectron spectroscopy (XPS) analyses, it is suggested that the higher content of metallic Pd caused by the addition of Tb contributes to the better catalytic activity of 20%Pd-1%Tb/C. Based on the good electrocatalytic performance of 20%Pd-1%Tb/C, the 20%Pd-1%Tb catalyst supported on poly(diallyldimethylammonium chloride) (PDDA)-functionalized activated carbon nanotubes was prepared, and it exhibits a better catalytic activity. The improvement mainly results from the further increase of metallic Pd due to the presence of PDDA.

  12. Efficacy and Safety of ‘Fixed Dose’ versus ‘Loose’ Drug Regimens for Treatment of Pulmonary Tuberculosis in Two High TB-Burden African Countries: A Randomized Controlled Trial

    PubMed Central

    2016-01-01

    Background There are limited data on the performance of the use of fixed-dose combination (FDC) TB drugs when used under programmatic settings in high TB-endemic countries. We evaluated the efficacy and safety of FDC versus loose formulation (LF) TB treatment regimens for treatment of pulmonary TB (PTB) in the context of actual medical practice in prevailing conditions within programmatic settings in five sites in two high TB-burden African countries. Methods A two-arm, single-blind, randomized clinical trial comparing FDCs with separate LFs involving 1000 adults newly diagnosed with culture positive PTB was conducted at five sites in two African countries between 2007 and 2011. Participants were randomized to receive daily treatment with anti-TB drugs given as either FDC or separate LFs for 24 weeks (intensive phase– 8 weeks of isoniazid, rifampicin, ethambutol and pyrazinamide; continuation phase– 16 weeks of rifampicin and isoniazid). Primary outcome measures were microbiological cure and safety at the end of six months’ treatment; pre-specified non-inferiority margin for difference in cure rate was 4%. The primary efficacy analysis was based on the modified intent to treat (mITT) cohort comprising all randomized patients with a positive baseline culture result for TB and who received at least one dose of study treatment. Patients missing end of treatment culture results were considered failures. Further analyses were done in which mITT patients without an end of treatment (EOT) culture were excluded in a complete case analysis (mITTcc) and a per protocol cohort analysis defined as mITTcc patients who received at least 95% of their intended doses and had an EOT culture result. Results In the mITT analysis, the cure rate in the FDC group was 86.7% (398/459) and in the LF group 85.2% (396/465) (difference 1.5-% (90% confidence interval (CI) (-2.2%– 5.3%)). Per Protocol analysis showed similar results: FDC 98.9% (359/363) versus LF 96.9% (345

  13. On the saturation of Tb phosphors under cathode-ray excitation. I. Excited-state absorption in Tb-activated phosphor powders

    NASA Astrophysics Data System (ADS)

    Nieuwesteeg, K. J. B. M.; Raue, R.; Busselt, W.

    1990-12-01

    Optical transitions between the 5D4 excited state of the Tb3+ (4f)8 configuration and the crystal-field split components of the (4f)7(5d) configuration are observed using high-resolution laser excitation of Tb-doped powder samples at room temperature. Excited-state absorption spectra of Tb3+ in YAG, YAGaG, Y2SiO5, and LaOBr are presented. Superimposed on the broadband excitation spectrum of these transitions we find the relatively narrow 4f→4f lines. We present a theoretical model for interpreting the 4f→5d transitions, which predicts a strict proportionality between the (4f)8 5D4→(4f)7(5d) and the (4f)8 7F6→(4f)7(5d) transitions. This model is used to estimate the optical-absorption cross section for the former transitions. Although the terminating 4f levels lie at the same energy as the 5d bands, the 4f→4f transitions can be interpreted on the basis of the Judd-Ofelt theory. We derived a method for calibration of the Tb3+ 4f→5d fluorescence-excitation spectra from powder samples. For YAG:Tb, the resulting optical cross sections were confirmed by direct-absorption measurements on a Tb3+ -doped epitaxial YAG layer. To our knowledge, this is the first time that the probabilities for excited-state absorption to highly excited 5d and 4f states in Tb3+ have been obtained theoretically and experimentally from Tb-doped powder materials.

  14. Diabetes and pulmonary tuberculosis: a global overview with special focus on the situation in Asian countries with high TB-DM burden

    PubMed Central

    Zheng, Chunlan; Hu, Minhui; Gao, Feng

    2017-01-01

    ABSTRACT Background: The double burden of tuberculosis (TB) and diabetes mellitus (DM) is hitting certain Asian countries harder than other areas. In a global estimate, 15% of all TB cases could be attributable to DM, with 40% of those cases coming from India and China. Many other countries of South, East, and South-East Asia are of particular concern given their TB burdens, large projected increases in DM prevalence, and population size. Objective: In this narrative review, we aimed to: (i) give an overall insight into the evidence on TB-DM epidemiology from high double burden Asian countries, (ii) present the evidence on bi-directional screening implementation in this region, (iii) discuss possible factors related to higher TB susceptibility of Asian diabetic patients, and (iv) identify TB-DM comorbidity treatment challenges. Methods: The PubMed and Google Scholar databases were searched for all studies addressing DM/TB epidemiology, bi-directional screening and management in South, East and South-East Asia. Results: We identified the DM prevalences among TB patients as ranging from approximately 5% to more than 50%, whereas TB prevalences among diabetic patients were 1.8–9.5 times higher than in the general population in developing Asian countries. Evidence from studies designed to address diagnosis and treatment of the dual disease in these critical regions is scarce as well as the evidence related to possible DM patients’ genetic and acquired predisposition for TB. Conclusion: More prospective studies specifically designed to address adequate screening techniques, identify patients at risk, and define an adequate treatment of dual disease in this region are needed without delay. PMID:28245710

  15. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.

    PubMed

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.

  16. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

    PubMed Central

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701

  17. Evaluation of the diagnostic value of measuring IgG, IgM, and IgA antibodies to mycobacterial A60 antigen in active tuberculosis.

    PubMed

    Ben-selma, Walid; Harizi, Hedi; Marzouk, Manel; Ben Kahla, Imen; Ben Lazreg, Foued; Ferjeni, Asma; Boukadida, Jalel

    2010-09-01

    The purpose of the present study was to evaluate the clinical usefulness of detection of serum immunoglobulin A (IgA), IgG, and IgM antibodies raised against the mycobacterial A60 antigen for the diagnosis and discrimination of active tuberculosis (TB) from other pulmonary diseases. Three commercially available ELISA kits (IgA, IgG, and IgM) (ANDA Biologicals, Strasbourg, France) were evaluated simultaneously in 246 serum samples from 3 groups of patients: group I, 171 patients with active TB (128 pulmonary TB and 43 extrapulmonary TB); group II, 73 patients with pulmonary non-TB diseases; and group III, 2 leprosies patients. The sensitivities of tests ranged from 31.3% (IgA) to 94% (IgG) in pulmonary TB patients and from 21% (IgA) to 84% (IgG) in extrapulmonary TB patients. The specificities of assays varied from 92% (IgG) to 96% (IgA) in the pulmonary non-TB group. Combination of IgG with IgA and/or IgM does not improve its sensitivity. Clinical use of the A60-based serodiagnostic IgG assay is of great value for the rapid diagnosis and discrimination between active TB and pulmonary non-TB diseases. Moreover, this test could be used to increase diagnostic accuracy, especially for smear-negative TB cases, which are difficult to diagnose.

  18. Amine oxidase activity regulates the development of pulmonary fibrosis.

    PubMed

    Marttila-Ichihara, Fumiko; Elima, Kati; Auvinen, Kaisa; Veres, Tibor Z; Rantakari, Pia; Weston, Christopher; Miyasaka, Masayuki; Adams, David; Jalkanen, Sirpa; Salmi, Marko

    2017-03-01

    In pulmonary fibrosis, an inflammatory reaction and differentiation of myofibroblasts culminate in pathologic deposition of collagen. Amine oxidase copper containing-3 (AOC3) is a cell-surface expressed oxidase that regulates leukocyte extravasation. Here we analyzed the potential role of AOC3 using gene-modified and inhibitor-treated mice in a bleomycin-induced pulmonary fibrosis model. Inflammation and fibrosis of lungs were assessed by histologic, flow cytometric, and quantitative PCR analysis. AOC3-deficient mice showed a 30-50% reduction in fibrosis, collagen synthesis, numbers of myofibroblasts, and accumulation of CD4(+) lymphocytes, NK T cells, macrophages, and type 2 innate lymphoid cells compared with wild-type control mice. AOC3 knock-in mice, which express a catalytically inactive form of AOC3, were also protected from lung fibrosis. In wild-type mice, a small-molecule AOC3 inhibitor treatment reduced leukocyte infiltration, myofibroblast differentiation, and fibrotic injury both in prophylactic and early therapeutic settings by about 50% but was unable to reverse the established fibrosis. AOC3 was also induced in myofibroblasts in human idiopathic pulmonary fibrosis. Thus, the oxidase activity of AOC3 contributes to the development of lung fibrosis mainly by regulating the accumulation of pathogenic leukocyte subtypes, which drive the fibrotic response.-Marttila-Ichihara, F., Elima, K., Auvinen, K., Veres, T. Z., Rantakari, P., Weston, C., Miyasaka, M., Adams, D., Jalkanen, S., Salmi, M. Amine oxidase activity regulates the development of pulmonary fibrosis.

  19. Validation of Mycobacterium tuberculosis Rv1681 Protein as a Diagnostic Marker of Active Pulmonary Tuberculosis

    PubMed Central

    Macovei, Lilia; Kanunfre, Kelly; Dhiman, Rakesh; Restrepo, Blanca I.; Zarate, Izelda; Pino, Paula A.; Mora-Guzman, Francisco; Fujiwara, Ricardo T.; Michel, Gerd; Kashino, Suely S.

    2013-01-01

    The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli-positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis. PMID:23390284

  20. Incremental Yield of Serial Sputum Cultures for Diagnosis of Tuberculosis among HIV Infected Smear Negative Pulmonary TB Suspects in Kampala, Uganda

    PubMed Central

    Ssengooba, Willy; Kiwanuka, Noah; Kateete, David P.; Katamba, Achilles; Joloba, Moses L.

    2012-01-01

    Background Sputum culture is the gold standard for diagnosis of pulmonary tuberculosis (PTB). Although mostly used for research, culture is recommended by the World Health Organization for TB diagnosis among HIV infected smear negative PTB suspects. Even then, the number of sputum samples required remains unspecified. Here, we determined the Incremental Yield (IY) and number of samples required to diagnose an additional PTB case upon second and third serial sputum culture. Methods/Findings This was a cross sectional study done between January and March 2011. Serial sputum samples were provided by participants within two days and cultured using Lowenstein Jensen (LJ) and Mycobacteria Growth Indicator Tube (MGIT) methods. A PTB case was defined as a positive culture on either one or both methods. The IY from the second and third serial cultures was determined and the reciprocal of the product of the fractions of IY provided the number of samples required for an additional PTB case. Of the 170 smear negative PTB suspects, 62 (36.5%) met the case definition. The IY of the second sample culture was 12.7%, 23.6% and 12.6% and for the third sample culture was 6.8%, 7.5% and 7.3% with LJ, MGIT and LJ or MGIT, respectively. The number of samples required for an additional PTB case and 95% CI upon the second sample culture were 29.9 (16.6, 156.5), 11.3 (7.6, 21.9) and 20.8 (12.5, 62.7); while for the third sample culture were 55.6 (26.4, 500.4), 35.7 (19.0, 313.8) and 36.1 (19.1, 330.9) by LJ, MGIT and LJ or MGIT respectively. Conclusions/Significance Among HIV infected smear negative PTB suspects in Kampala, 93% of PTB cases are diagnosed upon the second serial sputum culture. The number of cultures needed to diagnose an additional PTB case, ranges from 11–30 and 35–56 by the second and third sputum samples, respectively. PMID:22629439

  1. Immunochromatographic IgG/IgM Test for Rapid Diagnosis of Active Tuberculosis▿

    PubMed Central

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-01-01

    For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary TB [epTB]), (ii) 73 patients with pulmonary non-TB diseases, and (iii) two leprosy patients. The sensitivities of IgG and IgM in patients with active TB (pTB and epTB) were 68.4% and 2.3%, respectively. IgG had the best performance characteristics, with sensitivities of 78.1% and 39.5% in sera from patients with active pTB and epTB, respectively, and a specificity of 100%. The sensitivities of IgM were poor and were similar for pTB and epTB (2.3%). In contrast, specificity was very elevated (100%). The combination of IgG with IgM did not improve its sensitivity. IgG-mediated responses against the mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens might constitute a clinically useful tool for presumptive diagnosis and discrimination of active pTB from other pulmonary diseases. Moreover, based on its simplicity and rapidity of application, it could be a screening tool for active pTB in poorly equipped laboratories. PMID:21994352

  2. Immunochromatographic IgG/IgM test for rapid diagnosis of active tuberculosis.

    PubMed

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-12-01

    For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary TB [epTB]), (ii) 73 patients with pulmonary non-TB diseases, and (iii) two leprosy patients. The sensitivities of IgG and IgM in patients with active TB (pTB and epTB) were 68.4% and 2.3%, respectively. IgG had the best performance characteristics, with sensitivities of 78.1% and 39.5% in sera from patients with active pTB and epTB, respectively, and a specificity of 100%. The sensitivities of IgM were poor and were similar for pTB and epTB (2.3%). In contrast, specificity was very elevated (100%). The combination of IgG with IgM did not improve its sensitivity. IgG-mediated responses against the mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens might constitute a clinically useful tool for presumptive diagnosis and discrimination of active pTB from other pulmonary diseases. Moreover, based on its simplicity and rapidity of application, it could be a screening tool for active pTB in poorly equipped laboratories.

  3. Feasibility of Tissue Plasminogen Activator Formulated for Pulmonary Delivery

    PubMed Central

    Dunn, John S.; Nayar, Rajiv; Campos, Jackie; Hybertson, Brooks M.; Zhou, Yue; Manning, Mark Cornell; Repine, John E.; Stringer, Kathleen A.

    2007-01-01

    Purpose This study was conducted to assess the feasibility of a pulmonary formulation of tissue plasminogen activator (tPA) for nebulization into the airway by measuring protein stability, biologic activity, particle size, and estimating human lung distribution. Methods Formulations were derived by varying the surfactant and protein concentrations. Protein stability and recovery of each nebulized tPA formulation were assessed by ultraviolet spectroscopy. Formulations that met protein stability feasibility criteria were assessed for biologic and fibrinolytic activities. Biologic activity was determined by their ability to inhibit superoxide anion production by human neutrophils. Fibrinolytic activity was assessed by the cleavage of plasminogen to plasmin. Aerodynamic properties were assessed using a cascade impactor, and an estimation of human airway deposition was made via a human lung replica. Results Twenty-seven tPA formulations were initially assessed, 15 of which met protein stability criteria. Subsequently, three of these formulations maintained biologic and fibrinolytic activities. These formulations exhibited particle sizes of 2.4–3.1 μm, and had respirable doses ≥65%. A formulation of 1 mg mL−1 tPA and 0.1% Tween 80 exhibited a 45% deposition in the lower airways of a human lung replica. Conclusions A suitable pulmonary tPA formulation was identified that, following nebulization, maintained protein stability as well as biologic and fibrinolytic activities, and resulted in an optimal respirable dose and human airway deposition. This formulation may be applicable in the treatment of lung diseases, such as acute respiratory distress syndrome by permitting targeted pulmonary delivery of a therapeutic protein to the lungs. PMID:16180128

  4. Hsp90 regulation of fibroblast activation in pulmonary fibrosis

    PubMed Central

    Sontake, Vishwaraj; Wang, Yunguan; Kasam, Rajesh K.; Sinner, Debora; Reddy, Geereddy B.; Naren, Anjaparavanda P.; McCormack, Francis X.; Jegga, Anil G.; Madala, Satish K.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease associated with fibroblast activation that includes excessive proliferation, tissue invasiveness, myofibroblast transformation, and extracellular matrix (ECM) production. To identify inhibitors that can attenuate fibroblast activation, we queried IPF gene signatures against a library of small-molecule-induced gene-expression profiles and identified Hsp90 inhibitors as potential therapeutic agents that can suppress fibroblast activation in IPF. Although Hsp90 is a molecular chaperone that regulates multiple processes involved in fibroblast activation, it has not been previously proposed as a molecular target in IPF. Here, we found elevated Hsp90 staining in lung biopsies of patients with IPF. Notably, fibroblasts isolated from fibrotic lesions showed heightened Hsp90 ATPase activity compared with normal fibroblasts. 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a small-molecule inhibitor of Hsp90 ATPase activity, attenuated fibroblast activation and also TGF-β–driven effects on fibroblast to myofibroblast transformation. The loss of the Hsp90AB, but not the Hsp90AA isoform, resulted in reduced fibroblast proliferation, myofibroblast transformation, and ECM production. Finally, in vivo therapy with 17-AAG attenuated progression of established and ongoing fibrosis in a mouse model of pulmonary fibrosis, suggesting that targeting Hsp90 represents an effective strategy for the treatment of fibrotic lung disease. PMID:28239659

  5. [Tuberculosis Annual Report 2009--Series 6. Condition of TB (1)].

    PubMed

    2011-10-01

    The condition of tuberculosis (TB) at the time at which an individual is diagnosed with TB influences the patient's prognosis. This paper focuses on the condition of TB at the time of the diagnosis based on bacteriological status and X-ray findings. The proportion of bacteriologically confirmed cases among newly notified pulmonary TB patients increased greatly from 25.7% in 1979 to 82.7% in 2009. During this period, the proportion of far-advanced cavitary cases among pulmonary TB patients was around 2% and remained stable. This may mean that the diagnosis had come to be performed bacteriologically rather than radiologically. The proportion of bacteriologically confirmed cases among newly notified pulmonary TB patients in 2009 was studied by sex and 5-year age group. The proportion of bacteriologically confirmed cases increased with age in both male and female TB patients. In male TB patients, the proportion of cavitary cases increased in patients aged up to the end of the 50s and then decreased with age. This tendency was not observed in females. Although the proportion of cavitary cases among elderly TB patients was lower than among youths, the proportion having extensive lesions was greater than that among youths. The proportion of sputum-smear-positive cases with cavities among pulmonary TB patients aged 30-59 years was 32.9 % in male TB patients and 17.1% in female TB patients. According to occupation, this proportion was highest in "temporary workers" (52.6%) for male TB cases and "jobless/ others" (24.9%) for female TB cases, and lowest among "medical workers" in both sexes: 8.3% of male TB cases and 7.4% of female TB cases.

  6. Donor-derived tuberculosis (TB): isoniazid-resistant TB transmitted from a lung transplant donor with inadequately treated latent infection.

    PubMed

    Jensen, T O; Darley, D R; Goeman, E E; Shaw, K; Marriott, D J; Glanville, A R

    2016-10-01

    Donor-derived tuberculosis (TB) is an increasingly recognized complication of solid organ transplantation. We report a case of isoniazid-resistant pulmonary TB in a lung transplant recipient. The patient acquired the infection from the lung donor who was previously empirically treated with isoniazid for latent TB. The case highlights the caveat that, while adequate treatment of latent TB with isoniazid is presumed, meticulous screening of donors is required.

  7. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point

    PubMed Central

    Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K. Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G. Suarez, Pedro

    2016-01-01

    A child’s risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76–4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID:27196627

  8. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point.

    PubMed

    Tadesse, Yared; Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G Suarez, Pedro

    2016-01-01

    A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges.

  9. Diagnostic accuracy of chest radiography for the diagnosis of tuberculosis (TB) and its role in the detection of latent TB infection: a systematic review.

    PubMed

    Piccazzo, Riccardo; Paparo, Francesco; Garlaschi, Giacomo

    2014-05-01

    In this systematic review we evaluate the role of chest radiography (CXR) in the diagnostic flow chart for tuberculosis (TB) infection, focusing on latent TB infection (LTBI) in patients requiring medical treatment with biological drugs. In recent findings, patients scheduled for immunomodulatory therapy with biologic drugs are a group at risk of TB reactivation and, in such patients, detection of LTBI is of great importance. CXR for diagnosis of pulmonary TB has good sensitivity, but poor specificity. Radiographic diagnosis of active disease can only be reliably made on the basis of temporal evolution of pulmonary lesions. In vivo tuberculin skin test and ex vivo interferon-γ release assays are designed to identify development of an adaptive immune response, but not necessarily LTBI. Computed tomography (CT) is able to distinguish active from inactive disease. CT is considered a complementary imaging modality to CXR in the screening procedure to detect past and LTBI infection in specific subgroups of patients who have increased risk for TB reactivation, including those scheduled for medical treatment with biological drugs.

  10. TMC207 becomes bedaquiline, a new anti-TB drug.

    PubMed

    Palomino, Juan Carlos; Martin, Anandi

    2013-09-01

    TB still represents a serious public health problem. The latest reports estimate an incidence of 8.7 million cases in 2011 and 1.4 million deaths. Drug resistance contributed an estimated 630,000 cases of multidrug-resistant TB, making control of the disease harder. Recent reports show cases of TB that were almost resistant to all available antibiotics. Therefore, there is an urgent need to develop new anti-TB drugs with the potential of reducing the current length of treatment. Bedaquiline, formerly TMC207, is a new diarylquinoline antibiotic with specific activity against Mycobacterium tuberculosis and several nontuberculous mycobacteria. It acts by inhibiting ATP synthase, interfering with the energy generation needed by the bacterial cell. Based on clinical evaluations for safety, tolerability and efficacy, bedaquiline has recently received accelerated approval for the treatment of pulmonary multidrug-resistant TB in adults. This article will review the main aspects related to the chemistry, microbiology, pharmacology, efficacy and tolerability of bedaquiline.

  11. Testing for TB Infection

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  12. Measurement of the MACS of 159Tb(n, γ) at kT = 30 keV by Activation

    NASA Astrophysics Data System (ADS)

    Praena, J.; Mastinu, P. F.; Pignatari, M.; Quesada, J. M.; Capote, R.; Morilla, Y.

    2014-06-01

    The measurement of the Maxwellian-Averaged Cross-Section (MACS) of the 159Tb(n, γ) reaction at kT = 30 keV by the activation technique is presented. An innovative method for the generation of Maxwellian neutron spectra at kT = 30 keV is used. An experimental value of 2166 ± 181 mb agrees well with the MACS value derived from the ENDF/B-VII.1 evaluation, but is higher than KADoNiS recommended value of 1580 ± 150 mb. Astrophysical implications are studied.

  13. Immigrant screening for TB: a missed opportunity to improve TB control in the United Kingdom.

    PubMed

    Lalvani, Ajit; Pareek, Manish

    2012-03-01

    Tuberculosis in the United Kingdom and other high-income countries is primarily a disease of the foreign-born arising from the synergy of migration from high TB burden regions and the reactivation of remotely acquired latent TB infection. UK immigrant screening policy primarily aims to identify active, rather than latent, TB although mounting evidence indicates that implementing latent TB screening for new entrants from intermediate and high incidence countries could cost-effectively reduce TB incidence in the UK.

  14. Guidance from WHO on the prevention and control of TB during air travel.

    PubMed

    Martinez, Lindsay; Thomas, Kathrin; Figueroa, José

    2010-03-01

    Although tuberculosis (TB) is not highly transmissible, there is a risk of transmission of infection when close contact occurs between a person with active pulmonary TB and other passengers for prolonged periods during air travel. The World Health Organization first published Tuberculosis and air travel: guidelines for prevention and control in 1998, in response to several incidents involving TB in air travellers, with a second edition in 2006. A further revision was undertaken to address issues arising from the emergence of extensively resistant TB (XDR-TB), the occurrence of several international incidents involving TB and air travel, and the entry into force of the revised International Health Regulations (IHR) in 2007. This article describes the process followed in preparing the third edition, the special issues considered and the conclusions reached, with recommendations for travellers, physicians, public health authorities, and airline companies. New material includes: (i) additional guidance on the assessment of infectiousness, and on procedures, roles and responsibilities involved in the prevention of transmission of infection on board and for dealing with incidents; (ii) information on basic provisions of the IHR and measures relevant to incidents involving TB among air travellers; and (iii) a proposed procedure for carrying out contact investigations.

  15. Diagnosis of Pulmonary Tuberculosis: Recent Advances and Diagnostic Algorithms

    PubMed Central

    2015-01-01

    Pulmonary tuberculosis (TB) persists as a great public health problem in Korea. Increases in the overall age of the population and the rise of drug-resistant TB have reinforced the need for rapid diagnostic improvements and new modalities to detect TB and drug-resistant TB, as well as to improve TB control. Standard guidelines and recent advances for diagnosing pulmonary TB are summarized in this article. An early and accurate diagnosis of pulmonary TB should be established using chest X-ray, sputum microscopy, culture in both liquid and solid media, and nucleic acid amplification. Chest computed tomography, histopathological examination of biopsy samples, and new molecular diagnostic tests can be used for earlier and improved diagnoses, especially in patients with smear-negative pulmonary TB or clinically-diagnosed TB and drug-resistant TB. PMID:25861338

  16. Development of a Multicompartment Permeability-Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

    PubMed Central

    Gaohua, L; Wedagedera, J; Small, BG; Almond, L; Romero, K; Hermann, D; Hanna, D; Jamei, M; Gardner, I

    2015-01-01

    Achieving sufficient concentrations of antituberculosis (TB) drugs in pulmonary tissue at the optimum time is still a challenge in developing therapeutic regimens for TB. A physiologically based pharmacokinetic model incorporating a multicompartment permeability-limited lung model was developed and used to simulate plasma and pulmonary concentrations of seven drugs. Passive permeability of drugs within the lung was predicted using an in vitro-in vivo extrapolation approach. Simulated epithelial lining fluid (ELF):plasma concentration ratios showed reasonable agreement with observed clinical data for rifampicin, isoniazid, ethambutol, and erythromycin. For clarithromycin, itraconazole and pyrazinamide the observed ELF:plasma ratios were significantly underpredicted. Sensitivity analyses showed that changing ELF pH or introducing efflux transporter activity between lung tissue and ELF can alter the ELF:plasma concentration ratios. The described model has shown utility in predicting the lung pharmacokinetics of anti-TB drugs and provides a framework for predicting pulmonary concentrations of novel anti-TB drugs. PMID:26535161

  17. Thrombolytic Therapy by Tissue Plasminogen Activator for Pulmonary Embolism.

    PubMed

    Islam, Md Shahidul

    2017-01-01

    Clinicians need to make decisions about the use of thrombolytic (fibrinolytic) therapy for pulmonary embolism (PE) after carefully considering the risks of major complications from bleeding, and the benefits of treatment, for each individual patient. They should probably not use systemic thrombolysis for PE patients with normal blood pressure. Treatment by human recombinant tissue plasminogen activator (rt-PA), alteplase, saves the lives of high-risk PE patients, that is, those with hypotension or in shock. Even in the absence of strong evidence, clinicians need to choose the most appropriate regimen for administering alteplase for individual patients, based on assessment of the urgency of the situation, risks for major complications from bleeding, and patient's body weight. In addition, invasive strategies should be considered when absolute contraindications for thrombolytic therapy exist, serious complications arise, or thrombolytic therapy fails.

  18. Iron homeostasis and progression to pulmonary tuberculosis disease among household contacts.

    PubMed

    Minchella, Peter A; Donkor, Simon; McDermid, Joann M; Sutherland, Jayne S

    2015-05-01

    Early identification of individuals at risk for progressing to active tuberculosis (TB) disease may limit new transmission and improve clinical outcomes. Evidence indicates altered iron homeostasis may identify those at greater risk of disease progression in HIV co-infection. We aimed to investigate iron homeostasis biomarkers as risk factors for progression to TB. Archived plasma samples were analyzed from household contacts of pulmonary TB index cases in The Gambia. Contacts were classified as asymptomatic non-progressors (n = 17) or TB-progressors (n = 10), which included two HIV-infected participants. Iron homeostasis (hemoglobin, ferritin, hepcidin, soluble transferrin receptor, transferrin) was assessed in all contacts at study recruitment. Plasma was collected a median of 910 days prior to TB diagnosis. Low transferrin around the time of known exposure to infectious TB was a disease progression risk factor among all TB-progressors (Poisson incidence rate ratio: 0.55; 95% CI: 0.35-0.89). Iron homeostasis also differed between early and delayed TB-progressors, with higher ferritin and hepcidin concentrations observed among early TB-progressors (mean ferritin 50.2 vs. 26.2 ng/ml; P = 0.027; mean hepcidin 37.7 vs. 5.6 ng/ml; P = 0.036). Iron homeostasis is associated with progression to TB among household contacts. Further studies are needed to elucidate mechanisms and determine the clinical utility of monitoring iron homeostasis biomarkers.

  19. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging

    PubMed Central

    Heidt, Timo; Ehrismann, Simon; Hövener, Jan-Bernd; Neudorfer, Irene; Hilgendorf, Ingo; Reisert, Marco; Hagemeyer, Christoph E.; Zirlik, Andreas; Reinöhl, Jochen; Bode, Christoph; Peter, Karlheinz; von Elverfeldt, Dominik; von zur Muhlen, Constantin

    2016-01-01

    Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism. PMID:27138487

  20. Recent advances in testing for latent TB.

    PubMed

    Schluger, Neil W; Burzynski, Joseph

    2010-12-01

    After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of interferon γ release assays (IGRAs). These tests are generally associated with higher sensitivity and specificity for diagnosis of latent TB infection. This article reviews the indications for testing and treatment of latent TB infection in the overall context of a TB control program and describes how IGRAs might be used in specific clinical settings and populations, including people having close contact with an active case of TB, the foreign born, and health-care workers.

  1. Tuberculosis Facts - Testing for TB

    MedlinePlus

    Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  2. Tuberculosis Facts - Exposure to TB

    MedlinePlus

    Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  3. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia

    PubMed Central

    Hilliard, Kristie L.; Allen, Eri; Traber, Katrina E.; Kim, Yuri; Wasserman, Gregory A.; Jones, Matthew R.; Mizgerd, Joseph P.

    2015-01-01

    Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation and induce a robust acute-phase response (APR). Although APR activation is well regarded as a hallmark of infection, the direct contributions of liver activation to pulmonary defense during sepsis remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis and pneumonia. We employed a two-hit endotoxemia/pneumonia model, whereby administration of 18 h of intraperitoneal lipopolysaccharide (LPS; 5 mg/kg of body weight) was followed by intratracheal Escherichia coli (106 CFU) in wild-type mice or those lacking hepatocyte STAT3 (hepSTAT3−/−). Pneumonia alone (without endotoxemia) was effectively controlled in the absence of liver STAT3. Following endotoxemia and pneumonia, however, hepSTAT3−/− mice, with significantly reduced levels of circulating and airspace acute-phase proteins, exhibited significantly elevated lung and blood bacterial burdens and mortality. These data suggested that STAT3-dependent liver responses are necessary to promote host defense. While neither recruited airspace neutrophils nor lung injury was altered in endotoxemic hepSTAT3−/− mice, alveolar macrophage reactive oxygen species generation was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3−/− mice allowed greater bacterial growth ex vivo. These results suggest that hepatic STAT3 activation promotes both cellular and humoral lung defenses. Taken together, induction of liver STAT3-dependent gene expression programs is essential to countering the deleterious consequences of sepsis on pneumonia susceptibility. PMID:26216424

  4. Hydrothermal fabrication of multi-functional Eu3+ and Tb3+ co-doped BiPO4: Photocatalytic activity and tunable luminescence properties

    NASA Astrophysics Data System (ADS)

    Wang, Yao; Huang, Hongwei; Quan, Chaoming; Tian, Na; Zhang, Yihe

    2016-01-01

    We demonstrated for first time the tunable photoluminescence (PL) properties and photocatalytic activity of the Tb3+ and Eu3+ co-doped BiPO4 assemblies. They are fabricated via a facile hydrothermal approach. Through co-doping of Eu3+ and Tb3+ ions and changing the doping ratio, the emission color of the co-doped BiPO4 phosphors can be tuned precisely from green to yellow and red. Meanwhile, a very efficient energy transfer from Tb3+ to Eu3+ can be observed. Fascinatingly, a warmwhite color has been realized in the co-doped sample by tuning the ratio of Tb3+/Eu3+ to a certain value as displayed in the CIE chromaticity diagram. The doped BiPO4 samples also exhibit significantly enhanced photocatalytic activity compared to the pristine BiPO4 pertaining to Rhodamine (RhB) degradation under UV light. This enhancement should be attributed to the trapping electron effect induced by ion doping that endows BiPO4 with high separation of photoinduced electron-hole pairs, thereby greatly promoting the photocatalytic reactivity. It was corroborated by the electrochemical impedance spectra (EIS). Moreover, the crystal structure, microstructure and optical properties of as-prepared samples were investigated in details.

  5. Lessons learnt from TB screening in closed immigration centres in Italy

    PubMed Central

    Crepet, Anna; Repetto, Ernestina; Al Rousan, Ahmad; Sané Schepisi, Monica; Girardi, Enrico; Prestileo, Tullio; Codecasa, Luigi; Garelli, Silvia; Corrao, Salvatore; Ippolito, Giuseppe; Decroo, Tom; Maccagno, Barbara

    2016-01-01

    Background Between June 2012 and December 2013 Médecins Sans Frontières launched a pilot project with the aim of testing a strategy for improving timely diagnosis of active pulmonary TB among migrants hosted in four centres of identification and expulsion (CIE) in Italy. Methods This is a descriptive study. For active TB case finding we used an active symptom screening approach among migrants at admission in four CIE's. Here we describe the feasibility and the yield of this programme. Results Overall, 3588 migrants were screened, among whom 87 (2.4%) had a positive questionnaire. Out of 30 migrants referred for further investigations, three were diagnosed as having TB, or 0.1% out of 3588 individuals that underwent screening. Twenty-five (29%, 25/87) migrants with positive questionnaires were not referred for further investigation, following the doctors' decision; however, for 32 (37%, 32/87) migrants the diagnostic work-out was not completed. In multivariate analyses, being over 35 years (OR 1.7; 95% CI 1.1–2.6) and being transgender (OR 4.9; 95% CI 2.1–11.7), was associated with a positive questionnaire. Conclusions TB screening with symptom screening questionnaires of migrants at admission in closed centres is feasible. However, to improve the yield, follow-up of patients with symptoms or signs suggestive for TB needs to be improved. PMID:27208040

  6. Public Transportation and Pulmonary Tuberculosis, Lima, Peru

    PubMed Central

    Sánchez-Pérez, Héctor J.; Sánchez, Inma; Bedoya, Alfredo; Martín, Miguel

    2007-01-01

    The association between public transportation for commuting and pulmonary tuberculosis (TB) was analyzed in workers in Lima, Peru. Traveling in minibuses was a risk factor for pulmonary TB. Preventive measures need to be taken by health services to prevent spread of this disease. PMID:18257992

  7. VUV spectroscopic properties of rare-earth (RE3+ = Sm3+, Eu3+, Tb3+, Dy3+) -activated layered borate Ba6Gd9B79O138

    NASA Astrophysics Data System (ADS)

    Zhang, Zhi-Jun; Zhang, Shao-Lin; Zhang, Wei-Bin; Yang, Woochul

    2017-02-01

    Vacuum ultraviolet (VUV) spectroscopic properties of rare-earth RE3+- activated (RE3+ = Sm3+, Eu3+, Tb3+ and Dy3+) Ba6Gd9B79O138 borates (BGBO) are investigated. The strong absorption bands in the VUV range of un-doped and RE3+-activated BGBO were observed. The band range from 140 to 200 nm with a peak at about 173 nm results from the host lattice absorption. For Sm3+-activated BGBO, the charge transfer transition from O2- to Sm3+ was observed at 202 nm. In addition, it exhibits bright red emission originating from the Sm3+f-f transitions of 4G5/2 → 6HJ (J = 5/2, 7/2 and 9/2). The O2--Eu3+ charge transfer (CT) at 249 nm is observed in the excitation spectrum for Eu3+-doped BGBO. For Tb3+-activated BGBO, the broad bands around 208 and 230 nm are due to the spin-allowed and spin-forbidden f-d transitions of Tb3+, respectively. In addition, the absence of the f-d transitions of Sm3+ and Dy3+ in the excitation spectra probably due to the photo-ionization effect. It is demonstrated that there are energy transfers from the BGBO host lattice to the luminescent activators depending on the activators.

  8. Pulmonary tuberculosis

    MedlinePlus

    ... you have come into contact with the TB bacteria. It does not mean that you have active ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  9. A "turn-on" and label-free fluorescent assay for the rapid detection of exonuclease III activity based on Tb(3+)-induced G-quadruplex conjugates.

    PubMed

    Yang, WeiJuan; Ruan, YaJuan; Wu, WeiHua; Chen, PingPing; Xu, LiangJun; Fu, FengFu

    2014-07-01

    A "turn-on" and label-free fluorescent assay for the specific, rapid, and sensitive detection of 3' → 5' exonuclease III activity is reported in this study. The assay is based on the Tb(3+)-promoted G-quadruplex, which lead to the enhancement of Tb(3+) fluorescence due to the energy transfer from guanines. The proposed assay is highly simple, rapid, and cost-effective, and does not require sophisticated experimental techniques such as gel-based equipment or radioactive labels. It can be used for the rapid detection of exonuclease III activity with a detection limit of 0.8 U and a RSD (n = 6) <5 %. Notably, no dye was covalently conjugated to the DNA strands, which offers the advantages of low-cost and being interference-free.

  10. Immunity to TB and targets for immunotherapy.

    PubMed

    Gonzalez-Juarrero, Mercedes

    2012-02-01

    For centuries the treatment of TB has presented an enormous challenge to global health. In the 20th century, the treatment of TB patients with long-term multidrug therapy gave hope that TB could be controlled and cured; however, contrary to these expectations and coinciding with the emergence of AIDS, the world has witnessed a rampant increase in hard-to-treat cases of TB, along with the emergence of highly virulent and multidrug-resistant Mycobacterium tuberculosis strains. Unfortunately, these bacteria are now circulating around the world, and there are few effective drugs to treat them. As a result, the prospects for improved treatment and control of TB in the 21st century have worsened and we urgently need to identify new therapies that deal with this problem. The potential use of immunotherapy for TB is now of greater consideration than ever before, as immunotherapy could potentially overcome the problem of drug resistance. TB immunotherapy targets the already existing host anti-TB immune response and aims to enhance killing of the bacilli. For this purpose, several approaches have been used: the use of anti-Mycobacteria antibodies; enhancing the Th1 protective responses by using mycobacterial antigens or increasing Th1 cytokines; interfering with the inflammatory process and targeting of immunosuppressive pathways and targeting the cell activation/proliferation pathways. This article reviews our current understanding of TB immunity and targets for immunotherapy that could be used in combination with current TB chemotherapy.

  11. Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis.

    PubMed

    Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash

    2015-04-01

    Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4(+) T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8(+) T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8(+) T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8(+) T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8(+) T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8(+) T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8(+) T and NK cells, possibly contributing to increased pathology.

  12. [Start of TB case-registration and case-management system in Japan].

    PubMed

    Shimao, Tadao

    2010-07-01

    TB control in Japan started in 1951 through legislation of TB Control Law, consisting of three major components; mass health examination, vaccination and promotion of adequate methods of treatment for TB cases. Mass health examination was first targeted for younger generation below 30 years of age as it was believed that TB was highly prevalent among them, however, it was expanded to cover whole population based on the results of TB Prevalence Survey in 1953 revealing high prevalence of TB in all age groups except children and low awareness of TB cases. Methods of treatment for TB were developing rapidly in late 1950s and early 1960s; initially artificial pneumothorax, then surgical collapse treatment such as thoracoplasty, then pulmonary resection, and finally long term combined use of INH, SM and PAS. Up to surgical treatment era, most TB patients earnestly followed doctor's instruction, however, in chemotherapy era, as most symptoms improved rapidly after the initiation of chemotherapy, patients felt as if they were cured, and it had become difficult to maintain high adherence to treatment. Such behavior was found oftener in patients detected in early stage through mass health examinations. 1947, it was legislated for all doctors to report all diagnosed TB cases to an adjacent health center, and the cases are registered at the health center covering his (her) residence, however, standardized formula of registration was not indicated. In accordance with the progress of TB control program, the number of TB registered cases increased, and the need for standardized registration and case-management had become apparent in mid 1950s, and some preliminary trials had been done. In response to this request, the Ministry of Health and Welfare organized a research group headed by Dr. Misonou K, and the staffs of prefectural health department and enthusiastic staffs working in health centers (HCs), staffs of NIPH (National Institute of Public Health) and RIT (Research

  13. Treatment: Latent TB Infection (LTBI) and TB Disease

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  14. Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

    PubMed Central

    Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Qian, Fenghua; Ma, Qinglong; He, Mingdi; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

    2016-01-01

    With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs. PMID:27524893

  15. HIV and Tuberculosis (TB)

    MedlinePlus

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Tuberculosis (TB) (Last updated 9/1/2016; last reviewed ... depends on a person’s individual circumstances. What is tuberculosis? Tuberculosis (TB) is a contagious disease that can ...

  16. Tuberculosis (TB): Treatment

    MedlinePlus

    ... Training Home Conditions Tuberculosis (TB) Treating Tuberculosis Treating Tuberculosis Make an Appointment Refer a Patient Ask a ... bones is treated longer. NEXT: Preventive Treatment Diagnosing Tuberculosis History of TB Clinical Trials For more than ...

  17. Questions and Answers about TB

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  18. Dy(3)(+) -, Sm(3)(+) -, Ce(3)(+) - and Tb(3)(+) -activated optical properties of microcrystalline BaMgP2 O7 phosphors.

    PubMed

    Wani, J A; Dhoble, N S; Kokode, N S; Singh, Vijay; Dhoble, S J

    2017-03-01

    Photoluminescence (PL) and thermoluminescence (TL) properties of rare earth (RE) ion (RE = Dy(3)(+) , Sm(3)(+) , Ce(3)(+) , Tb(3)(+) ) activated microcrystalline BaMgP2 O7 phosphors are presented in this work. Non-doped and doped samples of BaMgP2 O7 were prepared using a solid state diffusion method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), PL and TL. The XRD measurement confirmed the phase purity of the BaMgP2 O7 host matrix. The average particle size was found through SEM measurement to be around 2 μm. All activators using the PL technique displayed characteristic excitation and emission spectra that corresponded to their typical f → f and f → d transitions respectively. Thermoluminescence measurements showed that BaMgP2 O7 :RE (RE = Dy(3)(+) , Sm(3)(+) , Tb(3)(+) , Ce(3)(+) ) and co-doped BaMgP2 O7 :Ce(3)(+) ,Tb(3)(+) phosphors have also TL behaviour.

  19. Role of superoxide anion on basal and stimulated nitric oxide activity in neonatal piglet pulmonary vessels.

    PubMed

    Villamor, Eduardo; Kessels, Carolina G A; Fischer, Marc A J; Bast, Aalt; de Mey, Jo G R; Blanco, Carlos E

    2003-09-01

    The superoxide anion (O2*-) appears to be an important modulator of nitric oxide bioavailability. Enzymatic scavenging of O2*- is carried out by superoxide dismutase (SOD). The present study was designed to characterize the developmental changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2) several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed age-related changes on pulmonary SOD activity and vascular O2*- levels. SOD (1-300 U/mL) produced endothelium-dependent relaxation of U46619-contracted intrapulmonary arteries (fourth branch) and veins from 12- to 24-h-old and 2-wk-old piglets. SOD-induced relaxation was greater in pulmonary arteries and was abolished by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in the 12- to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity in lung tissue did not change with postnatal age. With the use of dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find significant age- or vessel-related differences in O2*- presence. From the putative SOD mimetics tested, only the metal salts MnCl2 and CuSO4 reproduced the vascular effects of SOD. In summary, SOD produces endothelium-dependent pulmonary vascular relaxation by protecting nitric oxide from destruction by O2*-. This effect was less marked in newborns than in 2-wk-old piglets. In contrast, pulmonary arteries from newborn piglets are more sensitive to the inhibition of endogenous SOD.

  20. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  1. Recent tuberculosis diagnosis toward the end TB strategy.

    PubMed

    Cheon, Seon Ah; Cho, Hyun Hee; Kim, Jeonghyo; Lee, Jaebeom; Kim, Hwa-Jung; Park, Tae Jung

    2016-04-01

    Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis. Despite global TB eradication efforts, it is still a global public health concern, especially in low- and middle-income countries. Most of the active TB infections are curable with early diagnosis and appropriate treatment, but drug-resistant TB is difficult and expensive to treat in immunocompetent as well as immunocompromised individuals. Thus, rapid, economic, and accurate point-of care tools for TB diagnosis are required urgently. This review describes the history of M. tuberculosis detection methods up to date and the recent advances using nanotechnology for point-of-care testing of TB diagnosis.

  2. Impact of feedback on physical activity levels of individuals with chronic obstructive pulmonary disease during pulmonary rehabilitation: A feasibility study.

    PubMed

    Cruz, Joana; Brooks, Dina; Marques, Alda

    2014-11-01

    This study aimed at investigating whether providing feedback on physical activity (PA) levels to patients with chronic obstructive pulmonary disease (COPD) is feasible and enhances daily PA during pulmonary rehabilitation (PR). Patients with COPD participated in a 12-week PR program. Daily PA was measured using activity monitors on weeks 1, 7, and 12, and feedback was given in the following weeks on the number of steps, time spent in sedentary, light, and moderate-to-vigorous intensity activities, and time spent standing, sitting, and lying. Compliance with PA monitoring was collected. Two focus groups were conducted to obtain patients' perspectives on the use of activity monitors and on the feedback given. Differences in PA data were also assessed. Sixteen patients (65.63 ± 10.57 years; forced expiratory volume in one second (FEV1) 70.31 ± 22.74% predicted) completed the study. From those, only eleven participants used the activity monitors during all monitoring days. Participants identified several problems regarding the use of activity monitors and monitoring duration. Daily steps (p = 0.026) and standing time (p = 0.030) were improved from week 1 to week 7; however, the former declined from week 7 to week 12. Findings suggest that using feedback to improve PA during PR is feasible and results in improved daily steps and standing time on week 7. The subsequent decline suggests that additional strategies may be needed to stimulate/maintain PA improvements. Further research with more robust designs is needed to investigate the impact of feedback on patients' daily PA.

  3. Half of Pulmonary Tuberculosis Cases Were Left Undiagnosed in Prisons of the Tigray Region of Ethiopia: Implications for Tuberculosis Control

    PubMed Central

    Adane, Kelemework; Spigt, Mark; Ferede, Semaw; Asmelash, Tsehaye; Abebe, Markos; Dinant, Geert-Jan

    2016-01-01

    Introduction Prison settings have been often identified as important but neglected reservoirs for TB. This study was designed to determine the prevalence of undiagnosed pulmonary TB and assess the potential risk factors for such TB cases in prisons of the Tigray region. Method A cross-sectional study was conducted between August 2013 and February 2014 in nine prisons. A standardized symptom-based questionnaire was initially used to identify presumptive TB cases. From each, three consecutive sputum samples were collected for acid-fast bacilli (AFB) microscopy and culture. Blood samples were collected from consented participants for HIV testing. Result Out of 809 presumptive TB cases with culture result, 4.0% (95% CI: 2.65–5.35) were confirmed to have undiagnosed TB. The overall estimated point prevalence of undiagnosed TB was found to be 505/100,000 prisoners (95% CI: 360–640). Together with the 27 patients who were already on treatment, the overall estimated point prevalence of TB would be 793/100,000 prisoners (95% CI: 610–970), about four times higher than in the general population. The ratio of active to passive case detection was 1.18:1. The prevalence of HIV was 4.4% (36/809) among presumptive TB cases and 6.3% (2/32) among undiagnosed TB cases. In a multivariate logistic regression analysis, chewing Khat (adjusted OR = 2.81; 95% CI: 1.02–7.75) and having had a close contact with a TB patient (adjusted OR = 2.18; 95% CI: 1.05–4.51) were found to be predictors of undiagnosed TB among presumptive TB cases. Conclusions This study revealed that at least half of symptomatic pulmonary TB cases in Northern Ethiopian prisons remain undiagnosed and hence untreated. The prevalence of undiagnosed TB in the study prisons was more than two folds higher than in the general population of Tigray. This may indicate the need for more investment and commitment to improving TB case detection in the study prisons. PMID:26914770

  4. Antigen-Specific IFN-γ Responses Correlate with the Activity of M. tuberculosis Infection but Are Not Associated with the Severity of Tuberculosis Disease

    PubMed Central

    Nikitina, Irina Yu.; Panteleev, Alexander V.; Karpina, Natalya L.; Bagdasarian, Tatef R.; Burmistrova, Irina A.; Andreevskaya, Sofia N.; Chernousova, Larisa N.; Vasilyeva, Irina A.

    2016-01-01

    IFN-γ is a key cytokine in antituberculosis (TB) defense. However, how the levels of its secretion affect M. tuberculosis (Mtb) infection is not clear. We have analyzed associations between IFN-γ responses measured in QuantiFERON®-TB Gold In-tube (QFT) assay, TB disease severity, and Mtb infection activity. TB severity was evaluated based on the results of radiological, microbiological, and clinical examinations. Antigen-driven IFN-γ secretion did not correlate with TB severity. Mitogen-induced IFN-γ secretion correlated inversely with the form of pulmonary pathology and the area of affected pulmonary tissue; the levels of spontaneous IFN-γ secretion correlated with patients' age (r = 0.395, p = 0.001). Mtb infection activity was evaluated based on radiological data of lung tissue infiltration, destruction, dissemination or calcification, and condensation. The rate of positive QFT results and the levels of antigen-driven IFN-γ secretion increased in a row: patients with residual TB lesions < patients with low TB activity < patients with high TB activity. Thus, antigen-driven IFN-γ secretion and QFT results did not associate with TB severity but associated with the infection activity. The results suggest that quantitative parameters of IFN-γ secretion play a minor role in determining the course of TB disease but mirror the activity of the infectious process. PMID:28042583

  5. Antigen-Specific IFN-γ Responses Correlate with the Activity of M. tuberculosis Infection but Are Not Associated with the Severity of Tuberculosis Disease.

    PubMed

    Nikitina, Irina Yu; Panteleev, Alexander V; Sosunova, Ekaterina V; Karpina, Natalya L; Bagdasarian, Tatef R; Burmistrova, Irina A; Andreevskaya, Sofia N; Chernousova, Larisa N; Vasilyeva, Irina A; Lyadova, Irina V

    2016-01-01

    IFN-γ is a key cytokine in antituberculosis (TB) defense. However, how the levels of its secretion affect M. tuberculosis (Mtb) infection is not clear. We have analyzed associations between IFN-γ responses measured in QuantiFERON®-TB Gold In-tube (QFT) assay, TB disease severity, and Mtb infection activity. TB severity was evaluated based on the results of radiological, microbiological, and clinical examinations. Antigen-driven IFN-γ secretion did not correlate with TB severity. Mitogen-induced IFN-γ secretion correlated inversely with the form of pulmonary pathology and the area of affected pulmonary tissue; the levels of spontaneous IFN-γ secretion correlated with patients' age (r = 0.395, p = 0.001). Mtb infection activity was evaluated based on radiological data of lung tissue infiltration, destruction, dissemination or calcification, and condensation. The rate of positive QFT results and the levels of antigen-driven IFN-γ secretion increased in a row: patients with residual TB lesions < patients with low TB activity < patients with high TB activity. Thus, antigen-driven IFN-γ secretion and QFT results did not associate with TB severity but associated with the infection activity. The results suggest that quantitative parameters of IFN-γ secretion play a minor role in determining the course of TB disease but mirror the activity of the infectious process.

  6. Co-morbid anxiety and depression among pulmonary tuberculosis patients.

    PubMed

    Aamir, Siddiqua; Aisha

    2010-10-01

    The need to recognize and manage psychiatric co-morbidity in tuberculosis (TB) patients in primary care settings in order to improve adherence to the treatment is now well documented. Pulmonary TB patients at the District TB Control Office and TB Centre in Haripur from December 2007 to March 2008 were evalute in order to assess the frequency of anxiety and depression and continuation of treatment. Forty seven out of 65 (72%) TB patients had severe/moderate level of anxiety and depression according to Hospital Anxiety and Depression Scale (HADS). Fourteen (22%) TB patients with co-morbid anxiety and depression showed multi drug-resistance (MDR-TB).

  7. Idiopathic Pulmonary Hemosiderosis in a Child with Recurrent Macrophage Activation Syndrome Secondary to Systemic Juvenile Idiopathic Arthritis

    PubMed Central

    Barut, Kenan; Sahin, Sezgin; Adrovic, Amra

    2017-01-01

    Macrophage activation syndrome, a severe complication of systemic juvenile idiopathic arthritis and other inflammatory diseases, represents one of the most important rheumatological emergencies. Delayed diagnosis could lead to life-threatening complications. Pulmonary hemosiderosis has been classically characterized by a triad of anemia, hemoptysis, and lung infiltrates on chest radiogram. Although the majority of patients of pulmonary hemosiderosis are considered idiopathic, secondary hemosiderosis associated with known diseases could be seen. In this case report, we aimed to present gradually increased pulmonary manifestations due to pulmonary hemosiderosis with recurrent macrophage activation syndrome attacks in a child with systemic juvenile idiopathic arthritis. PMID:28251009

  8. Effects of gender and age on development of concurrent extrapulmonary tuberculosis in patients with pulmonary tuberculosis: a population based study.

    PubMed

    Lin, Chun-Yu; Chen, Tun-Chieh; Lu, Po-Liang; Lai, Chung-Chih; Yang, Yi-Hsin; Lin, Wei-Ru; Huang, Pei-Ming; Chen, Yen-Hsu

    2013-01-01

    Most cases of adult-onset tuberculosis (TB) result from reactivation of a pre-existing Mycobacterium tuberculosis infection. Mycobacterium tuberculosis usually invades the respiratory tract and most patients develop intrapulmonary TB; however, some patients develop concurrent pulmonary and extra-pulmonary TB. The purpose of the present study was to identify the demographic and clinical factors associated with an increased risk of concurrent extra-pulmonary diseases in patients with pulmonary TB. We compared patients who had isolated pulmonary TB with patients who had concurrent pulmonary and extra-pulmonary TB. We initially analyzed one-million randomly selected subjects from the population-based Taiwan National Health Insurance database. Based on analysis of 5414 pulmonary TB patients in this database, women were more likely than men to have concurrent extra-pulmonary TB (OR: 1.30, p = 0.013). A separate analysis of the Kaohsiung Medical University Hospital database, which relied on sputum culture-proven pulmonary TB, indicated that women were more likely than men to have concurrent extra-pulmonary TB (OR: 1.62, p = 0.039). There was no significant gender difference in extra-pulmonary TB for patients younger than 45 years in either database. However, for patients 45 years and older, women were more likely than men to have concurrent extra-pulmonary TB (insurance database: 9.0% vs. 6.8%, p = 0.016, OR: 1.36; hospital database: 27.3% vs. 16.0%, p = 0.008, OR = 1.98). Our results indicate that among patients who have pulmonary TB, older females have an increased risk for concurrent extra-pulmonary TB.

  9. Rapid identification of tuberculosis epididymo-orchitis by INNO-LiPA Rif TB and QuantiFERON-TB Gold In Tube tests: case report.

    PubMed

    Paluch-Oleś, Jolanta; Magryś, Agnieszka; Kot, Ewa; Kozioł-Montewka, Maria

    2010-03-01

    Diagnosis of extrapulmonary tuberculosis (TB) is often missed or delayed because of nonspecific clinical and laboratory findings. Novel detection methods, such as polymerase chain reaction and QuantiFERON-TB Gold In Tube, can aid in the diagnosis of active extrapulmonary TB. Here, we demonstrate a case of epididymo-orchitis as the sole presentation of TB in a 32-year-old man.

  10. Pulmonary Epithelial TLR4 Activation Leads to Lung Injury in Neonatal Necrotizing Enterocolitis.

    PubMed

    Jia, Hongpeng; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Lu, Peng; Martin, Laura Y; Good, Misty; Zhou, Qinjie; Sung, Jungeun; Fulton, William B; Nino, Diego F; Prindle, Thomas; Ozolek, John A; Hackam, David J

    2016-08-01

    We seek to define the mechanisms leading to the development of lung disease in the setting of neonatal necrotizing enterocolitis (NEC), a life-threatening gastrointestinal disease of premature infants characterized by the sudden onset of intestinal necrosis. NEC development in mice requires activation of the LPS receptor TLR4 on the intestinal epithelium, through its effects on modulating epithelial injury and repair. Although NEC-associated lung injury is more severe than the lung injury that occurs in premature infants without NEC, the mechanisms leading to its development remain unknown. In this study, we now show that TLR4 expression in the lung gradually increases during postnatal development, and that mice and humans with NEC-associated lung inflammation express higher levels of pulmonary TLR4 than do age-matched controls. NEC in wild-type newborn mice resulted in significant pulmonary injury that was prevented by deletion of TLR4 from the pulmonary epithelium, indicating a role for pulmonary TLR4 in lung injury development. Mechanistically, intestinal epithelial TLR4 activation induced high-mobility group box 1 release from the intestine, which activated pulmonary epithelial TLR4, leading to the induction of the neutrophil recruiting CXCL5 and the influx of proinflammatory neutrophils to the lung. Strikingly, the aerosolized administration of a novel carbohydrate TLR4 inhibitor prevented CXCL5 upregulation and blocked NEC-induced lung injury in mice. These findings illustrate the critical role of pulmonary TLR4 in the development of NEC-associated lung injury, and they suggest that inhibition of this innate immune receptor in the neonatal lung may prevent this devastating complication of NEC.

  11. Plasma Metabolomics in Human Pulmonary Tuberculosis Disease: A Pilot Study

    PubMed Central

    Frediani, Jennifer K.; Jones, Dean P.; Tukvadze, Nestan; Uppal, Karan; Sanikidze, Eka; Kipiani, Maia; Tran, ViLinh T.; Hebbar, Gautam; Walker, Douglas I.; Kempker, Russell R.; Kurani, Shaheen S.; Colas, Romain A.; Dalli, Jesmond; Tangpricha, Vin; Serhan, Charles N.; Blumberg, Henry M.; Ziegler, Thomas R.

    2014-01-01

    We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers

  12. Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down-Referred from a District Hospital to Primary Health Clinics in Rural South Africa

    PubMed Central

    Jacobson, Karen B.; Moll, Anthony P.; Friedland, Gerald H.; Shenoi, Sheela V.

    2015-01-01

    Background HIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa. Methods We retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients’ demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes. Results Of 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC. Conclusion Decentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased

  13. Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease

    PubMed Central

    Borchers, Michael T.; Wesselkamper, Scott C.; Curull, Victor; Ramirez-Sarmiento, Alba; Sánchez-Font, Albert; Garcia-Aymerich, Judith; Coronell, Carlos; Lloreta, Josep; Agusti, Alvar G.; Gea, Joaquim; Howington, John A.; Reed, Michael F.; Starnes, Sandra L.; Harris, Nathaniel L.; Vitucci, Mark; Eppert, Bryan L.; Motz, Gregory T.; Fogel, Kevin; McGraw, Dennis W.; Tichelaar, Jay W.; Orozco-Levi, Mauricio

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early transcript 1 (RAET1) as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies. PMID:19197141

  14. ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON?

    EPA Science Inventory

    ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON? UP Kodavanti1, MCJ Schladweiler1, S Becker2, DL Costa1, P Mayer3, A Ziesenis3, WG Kreyling3, 1ETD, 2HSDivision, NHEERL, USEPA, Research Triangle Park, NC, USA, and 3GSF, Inhalation Biology...

  15. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  16. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  17. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  18. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  19. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  20. Early and Extended Early Bactericidal Activity of Linezolid in Pulmonary Tuberculosis

    PubMed Central

    Dietze, Reynaldo; Hadad, David Jamil; McGee, Bryan; Molino, Lucilia Pereira Dutra; Maciel, Ethel Leonor Noia; Peloquin, Charles A.; Johnson, Denise F.; Debanne, Sara M.; Eisenach, Kathleen; Boom, W. Henry; Palaci, Moises; Johnson, John L.

    2008-01-01

    Rationale: Linezolid, the first oxazolidinone approved for clinical use, has effective in vitro and promising in vivo activity against Mycobacterium tuberculosis. Objectives: To evaluate the early and extended early bactericidal activity of linezolid in patients with pulmonary tuberculosis. Methods: Randomized open label trial. Thirty patients with newly diagnosed smear-positive pulmonary tuberculosis (10 per arm) were assigned to receive isoniazid (300 mg daily) and linezolid (600 mg twice daily or 600 mg once daily) for 7 days. Sputum for quantitative culture was collected for 2 days before and then daily during 7 days of study drug administration. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (early bactericidal activity) and the last 5 days of study drug administration (extended early bactericidal activity). Measurements and Main Results: The mean early bactericidal activity of isoniazid (0.67 log10 cfu/ml/d) was greater than that of linezolid twice and once daily (0.26 and 0.18 log10 cfu/ml/d, respectively). The extended early bactericidal activity of linezolid between Days 2 and 7 was minimal. Conclusions: Linezolid has modest early bactericidal activity against rapidly dividing tubercle bacilli in patients with cavitary pulmonary tuberculosis during the first 2 days of administration, but little extended early bactericidal activity. Clinical trial registered with www.clinicaltrials.gov (NCT00396084). PMID:18787216

  1. Expression of peptide fragments from proADM and involvement of mitogen-activated protein kinase signaling pathways in pulmonary remodeling induced by high pulmonary blood flow.

    PubMed

    Li, Wei; Guo, Aili; Wang, Lijuan; Kong, Qingyu; Wang, Rong; Han, Li; Zhao, Cuifen

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary arterial remodeling and right ventricular failure. Despite recent advances in pathophysiological mechanism exploration and new therapeutic approaches, PAH remains a challenging condition. In this study, we investigated the roles of the peptide fragments from proadrenomedullin (proADM) such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N-terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary blood flow, and probed the possible involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were artificially established by surgically connecting the left common carotid artery to the external jugular vein. We subcutaneously injected an extracellular signal-regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated another eight rats with an equal volume of saline. Eight rats without connections served as the control group. We observed that mRNA expression levels of ADM, stress-activated protein kinase (SAPK), and ERK1/2 were significantly elevated in the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by PD98059. Protein levels of ADM, PAMP, p-SAPK, and p-ERK1/2 were significantly higher ADT was lower, and p-p38 remained unchanged in the rat models compared with the controls. However, the protein expression of both ADM and p-ERK1/2 was significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT, and PAMP respond to pulmonary remodeling, and that activation of the SAPK and ERK1/2 signaling pathways is involved in pulmonary hypertension and artery remodeling caused by high pulmonary blood flow.

  2. Non-pulmonary tuberculosis.

    PubMed

    Carrol, E D; Clark, J E; Cant, A J

    2001-06-01

    Tuberculosis (TB) is a serious disease of global importance, with a rising incidence in the developed world in recent years. Tuberculous lymphadenitis, tuberculous meningitis, osteoarticular tuberculosis and miliary tuberculosis are some of the more well-recognised manifestations of non-pulmonary TB in childhood. The diagnosis of non-pulmonary TB poses a particular challenge for clinicians because of the protean ways in which the disease presents. The omission of tuberculosis from the differential diagnosis of patients with obscure illnesses and the relatively insensitive bacteriological methods for detecting Mycobacterium tuberculosis add to the complexity of the problem. A high index of suspicion is required in order to avoid delays in diagnosis which may influence treatment outcome. The advent of DNA amplification techniques such as the polymerase chain reaction may herald a promising new era in the prompt and accurate management of extrapulmonary tuberculosis.

  3. Association between physical activity in daily life and pulmonary function in adult smokers

    PubMed Central

    Barboza, Miriane Lilian; Barbosa, Alan Carlos Brisola; Spina, Giovanna Domingues; Sperandio, Evandro Fornias; Arantes, Rodolfo Leite; Gagliardi, Antonio Ricardo de Toledo; Romiti, Marcello; Dourado, Victor Zuniga

    2016-01-01

    Objective: To determine whether the level of physical activity in daily life (PADL) is associated with pulmonary function in adult smokers. Methods: We selected 62 adult smokers from among the participants of an epidemiological study conducted in the city of Santos, Brazil. The subjects underwent forced spirometry for pulmonary function assessment. The level of PADL was assessed by the International Physical Activity Questionnaire and triaxial accelerometry, the device being used for seven days. The minimum level of PADL, in terms of quantity and intensity, was defined as 150 min/week of moderate to vigorous physical activity. Correlations between the studied variables were tested with Pearson's or Spearman's correlation coefficient, depending on the distribution of the variables. We used linear multiple regression in order to analyze the influence of PADL on the spirometric variables. The level of significance was set at 5%. Results: Evaluating all predictors, corrected for confounding factors, and using pulmonary function data as outcome variables, we found no significant associations between physical inactivity, as determined by accelerometry, and spirometric indices. The values for FVC were lower among the participants with arterial hypertension, and FEV1/FVC ratios were lower among those with diabetes mellitus. Obese participants and those with dyslipidemia presented with lower values for FVC and FEV1. Conclusions: Our results suggest that there is no consistent association between physical inactivity and pulmonary function in adult smokers. Smoking history should be given special attention in COPD prevention strategies, as should cardiovascular and metabolic comorbidities. PMID:27167434

  4. Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans

    PubMed Central

    Velez, Digna Rosa; Wejse, Christian; Stryjewski, Martin E.; Abbate, Eduardo; Hulme, William F.; Myers, Jamie L.; Estevan, Rosa; Patillo, Sara G.; Olesen, Rikke; Tacconelli, Alessandra; Sirugo, Giorgio; Gilbert, John R.; Hamilton, Carol D.; Scott, William K.

    2010-01-01

    Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (−196 to −174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR=0.41 [95% CI 0.24–0.68], p=0.0007) and Africans (II vs. ID&DD, OR=0.70 [95% CI 0.51–0.95], p=0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB. PMID:19771452

  5. Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension

    PubMed Central

    Forrest, Abigail S.; Joyce, Talia C.; Huebner, Marissa L.; Ayon, Ramon J.; Wiwchar, Michael; Joyce, John; Freitas, Natalie; Davis, Alison J.; Ye, Linda; Duan, Dayue D.; Singer, Cherie A.; Valencik, Maria L.; Greenwood, Iain A.

    2012-01-01

    Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca2+ levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca2+-activated Cl− channels (ClCa), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of ClCa channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks postinjection with a single dose of MCT (50 mg/kg ip), the animals developed right ventricular hypertrophy (heart weight measurements) and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca2+-activated Cl− current [ICl(Ca)] density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats vs. aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in ICl(Ca) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for ClCa channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 μM), an l-type Ca2+ channel blocker, and NFA (30 or 100 μM, with or without 10 μM indomethacin to inhibit cyclooxygenases) or T16AInh-A01 (10 μM), TMEM16A/ClCa channel inhibitors, than that of control animals. In conclusion, augmented ClCa/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease. PMID:23034390

  6. Stimulus Response of Au-NPs@GMP-Tb Core-Shell Nanoparticles: Toward Colorimetric and Fluorescent Dual-Mode Sensing of Alkaline Phosphatase Activity in Algal Blooms of a Freshwater Lake.

    PubMed

    Zhang, Xiaolei; Deng, Jingjing; Xue, Yumeng; Shi, Guoyue; Zhou, Tianshu

    2016-01-19

    In this study, we demonstrate a colorimetric and fluorescent dual-mode method for alkaline phosphatase activity (APA) sensing in freshwater lake with stimuli-responsive gold nanoparticles@terbium-guanosine monophosphate (Au-NPs@GMP-Tb) core-shell nanoparticles. Initially, the core-shell nanoparticles were fabricated based on Au-NPs decorated with a fluorescent GMP-Tb shell. Upon being excited at 290 nm, the as-formed Au-NPs@GMP-Tb core-shell nanoparticles emit green fluorescence, and the decorated GMP-Tb shell causes the aggregation of Au-NPs. However, the addition of ALP destroys GMP-Tb shell, resulting in the release of Au-NPs from the shell into the solvent. As a consequence, the aggregated Au-NPs solubilizes with the changes in the UV-vis spectrum of the dispersion, and in the meantime, the fluorescence of GMP-Tb shell turns off, which constitutes a new mechanism for colorimetric and fluorescent dual-mode sensing of APA. With the method developed here, we could monitor the dynamic change of APA during an algal bloom of a freshwater lake, both by the naked eye and further confirmed by fluorometric determination. This study not only offers a new method for on-site visible detection of APA but also provides a strategy for dual-mode sensing mechanisms by the rational design of the excellent optical properties of Au-NPs and the adaptive inclusion properties of the luminescent infinite coordination polymers.

  7. Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

    PubMed Central

    Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

    2015-01-01

    Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

  8. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

    SciTech Connect

    Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

    2015-09-25

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

  9. Nuclear Factor κ-B Is Activated in the Pulmonary Vessels of Patients with End-Stage Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Price, Laura C.; Caramori, Gaetano; Perros, Frederic; Meng, Chao; Gambaryan, Natalia; Dorfmuller, Peter; Montani, David; Casolari, Paolo; Zhu, Jie; Dimopoulos, Konstantinos; Shao, Dongmin; Girerd, Barbara; Mumby, Sharon; Proudfoot, Alastair; Griffiths, Mark; Papi, Alberto; Humbert, Marc; Adcock, Ian M.; Wort, S. John

    2013-01-01

    Objectives To assess activation of the inflammatory transcription factor NF-kappa B (NF-κB) in human idiopathic pulmonary arterial hypertension (PAH). Background Idiopathic PAH is a severe progressive disease characterized by pulmonary vascular remodeling and excessive proliferation of vascular cells. Increasing evidence indicates that inflammation is important in disease pathophysiology. Methods NF-κB-p65 and CD68, CD20 and CD45 were measured by immunohistochemistry and confocal microscopy on lung specimens from patients with idiopathic PAH (n = 12) and controls undergoing lung surgery (n = 14). Clinical data were recorded for all patients including invasive pulmonary hemodynamics for the PAH patients. Immunohistochemical images were analyzed by blinded observers to include standard pulmonary vascular morphometry; absolute macrophage counts/mm2 and p65-positivity (p65+) using composite images and image-analysis software; and cytoplasmic:nuclear p65+ of individual pulmonary arterial endothelial and smooth muscle cells (PASMC) in 10–20 pulmonary arteries or arterioles per subject. The expression of ET-1 and CCL5 (RANTES) in whole lung was determined by RT-qPCR. Results Macrophage numbers were increased in idiopathic PAH versus controls (49.0±4.5 vs. 7.95±1.9 macrophages/100 mm2, p<0.0001): these macrophages demonstrated more nuclear p65+ than in macrophages from controls (16.9±2.49 vs. 3.5±1.25%, p<0.001). An increase in p65+ was also seen in perivascular lymphocytes in patients with PAH. Furthermore, NF-κB activation was increased in pulmonary arterial endothelial cells (62.3±2.9 vs. 14.4±3.8, p<0.0001) and PASMC (22.6±2.3 vs. 11.2±2.0, p<0.001) in patients with PAH versus controls, with similar findings in arterioles. Gene expression of both ET-1 mRNA ((0.213±0.069 vs. 1.06±0.23, p<0.01) and CCL5 (RANTES) (0.16±0.045 vs. 0.26±0.039, p<0.05) was increased in whole lung homogenates from patients with PAH. Conclusions NF-κB is activated in

  10. Vagal nerve activity contributes to improve the efficiency of pulmonary gas exchange in hypoxic humans.

    PubMed

    Ito, Shoji; Sasano, Hiroshi; Sasano, Nobuko; Hayano, Junichiro; Fisher, Joseph A; Katsuya, Hirotada

    2006-09-01

    The aim of this study was to test our hypothesis that both phasic cardiac vagal activity and tonic pulmonary vagal activity, estimated as respiratory sinus arrhythmia (RSA) and anatomical dead space volume, respectively, contribute to improve the efficiency of pulmonary gas exchange in humans. We examined the effect of blocking vagal nerve activity with atropine on pulmonary gas exchange. Ten healthy volunteers inhaled hypoxic gas with constant tidal volume and respiratory frequency through a respiratory circuit with a respiratory analyser. Arterial partial pressure of O(2) (P(aO(2))) and arterial oxygen saturation (S(pO(2))) were measured, and alveolar-to-arterial P(O(2)) difference (D(A-aO(2))) was calculated. Anatomical dead space (V(D,an)), alveolar dead space (V(D,alv)) and the ratio of physiological dead space to tidal volume (V(D,phys)/V(T)) were measured. Electrocardiogram was recorded, and the amplitude of R-R interval variability in the high-frequency component (RRIHF) was utilized as an index of RSA magnitude. These parameters of pulmonary function were measured before and after administration of atropine (0.02 mg kg(-1)). Decreased RRIHF (P < 0.01) was accompanied by decreases in P(aO(2)) and S(pO(2)) (P < 0.05 and P < 0.01, respectively) and an increase in D(A-aO(2)) (P < 0.05). Anatomical dead space, V(D,alv) and V(D,phys)/V(T) increased (P < 0.01, P < 0.05 and P < 0.01, respectively) after atropine administration. The blockade of the vagal nerve with atropine resulted in an increase in V(D,an) and V(D,alv) and a deterioration of pulmonary oxygenation, accompanied by attenuation of RSA. Our findings suggest that both phasic cardiac and tonic pulmonary vagal nerve activity contribute to improve the efficiency of pulmonary gas exchange in hypoxic conscious humans.

  11. Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells.

    PubMed

    Nydam, Trevor L; Moore, Ernest E; McIntyre, Robert C; Wright, Franklin L; Gamboni-Robertson, Fabia; Eckels, Phillip C; Banerjee, Anirban

    2009-05-01

    Resuscitation with hypertonic saline (HTS) attenuates acute lung injury (ALI) and modulates postinjury hyperinflammation. TNF-alpha-stimulated pulmonary epithelium is a major contributor to hemorrhage-induced ALI. We hypothesized that HTS would inhibit TNF-alpha-induced nuclear factor (NF)-kappaB proinflammatory signaling in pulmonary epithelial cells. Therefore, we pretreated human pulmonary epithelial cells (A549) with hypertonic medium (180 mM NaCl) for 30 min, followed by TNF-alpha stimulation (10 ng/mL). Key regulatory steps and protein concentrations in this pathway were assessed for significant alterations. Hypertonic saline significantly reduced TNF-alpha-induced intercellular adhesion molecule 1 levels and NF-kappaB nuclear localization. The mechanism is attenuated phosphorylation and delayed degradation of IkappaB alpha. Hypertonic saline did not alter TNF-alpha-induced p38 mitogen-activated protein kinase phosphorylation or constitutive vascular endothelial growth factor expression, suggesting that the observed inhibition is not a generalized suppression of protein phosphorylation or cellular function. These results show that HTS inhibits TNF-alpha-induced NF-kappaB activation in the pulmonary epithelium and, further, our understanding of its beneficial effects in hemorrhage-induced ALI.

  12. TB Is Back.

    ERIC Educational Resources Information Center

    Natale, Jo Anna

    1992-01-01

    The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…

  13. TAIMA (Stop) TB: The Impact of a Multifaceted TB Awareness and Door-to-Door Campaign in Residential Areas of High Risk for TB in Iqaluit, Nunavut

    PubMed Central

    Alvarez, Gonzalo G.; VanDyk, Deborah D.; Aaron, Shawn D.; Cameron, D. William; Davies, Naomi; Stephen, Natasha; Mallick, Ranjeeta; Momoli, Franco; Moreau, Katherine; Obed, Natan; Baikie, Maureen; Osborne, Geraldine

    2014-01-01

    Background The incidence rate of active tuberculosis (TB) disease in the Canadian Territory of Nunavut has shown a rising trend over the past 10 years. In 2010 it was 60 times greater than the national incidence rate. The objective of the Taima (translates to “stop” in Inuktitut) TB study was to implement and evaluate a public health campaign to enhance existing TB prevention efforts in Nunavut. Methods A TB awareness campaign followed by a door-to-door screening campaign was carried out in Iqaluit, Nunavut. The aim of the campaign was to raise awareness about TB, and to provide in-home screening and treatment for people living in residential areas at high risk for TB. Screening was based on geographic location rather than on individual risk factors. Results During the general awareness campaign an increase in the number of people who requested TB testing at the local public health clinic was observed. However, this increase was not sustained following cessation of the awareness campaign. Targeted TB screening in high risk residential areas in Iqaluit resulted in 224 individuals having TSTs read, and detection of 42 previously unidentified cases of latent TB, (overall yield of 18.8% or number needed to screen = 5.3). These cases of latent TB infection (LTBI) were extra cases that had not been picked up by traditional screening practices (34% relative increase within the community). This resulted in a 33% relative increase in the completion of LTBI treatment within the community. The program directly and indirectly identified 5/17 new cases of active TB disease in Iqaluit during the study period (29.5% of all incident cases). Conclusions While contact tracing investigations remain a cornerstone of TB prevention, additional awareness, screening, and treatment programs like Taima TB may contribute to the successful control of TB in Aboriginal communities. PMID:25033320

  14. Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity.

    PubMed

    Burgy, Olivier; Wettstein, Guillaume; Bellaye, Pierre S; Decologne, Nathalie; Racoeur, Cindy; Goirand, Françoise; Beltramo, Guillaume; Hernandez, Jean-François; Kenani, Abderraouf; Camus, Philippe; Bettaieb, Ali; Garrido, Carmen; Bonniaud, Philippe

    2016-02-17

    Bleomycin (BLM) is a potent anticancer drug used to treat different malignancies, mainly lymphomas, germ cell tumors, and melanomas. Unfortunately, BLM has major, dose-dependent, pulmonary toxicity that affects 20% of treated individuals. The most severe form of BLM-induced pulmonary toxicity is lung fibrosis. Deglyco-BLM is a molecule derived from BLM in which the sugar residue d-mannosyl-l-glucose disaccharide has been deleted. The objective of this study was to assess the anticancer activity and lung toxicity of deglyco-BLM. We compared the antitumor activity and pulmonary toxicity of intraperitoneally administrated deglyco-BLM and BLM in three rodent models. Pulmonary toxicity was examined in depth after intratracheal administration of both chemotherapeutic agents. The effect of both drugs was further studied in epithelial alveolar cells in vitro. We demonstrated in rodent cancer models, including a human Hodgkin's lymphoma xenograft and a syngeneic melanoma model, that intraperitoneal deglyco-BLM is as effective as BLM in inducing tumor regression. Whereas the antitumor effect of BLM was accompanied by a loss of body weight and the development of pulmonary toxicity, deglyco-BLM did not affect body weight and did not engender lung injury. Both molecules induced lung epithelial cell apoptosis after intratracheal administration, but deglyco-BLM lost the ability to induce caspase-1 activation and the production of ROS (reactive oxygen species), transforming growth factor-β1, and other profibrotic and inflammatory cytokines in the lungs of mice and in vitro. Deglyco-BLM should be considered for clinical testing as a less toxic alternative to BLM in cancer therapy.

  15. COUNTING THE MISSING CASES: ESTIMATING THE GLOBAL BURDEN OF MULTIDRUG-RESISTANT TUBERCULOSIS AMONG PREVALENT CASES OF TB

    PubMed Central

    Nourzad, Susan; Jenkins, Helen E.; Milstein, Meredith; Mitnick, Carole D.

    2017-01-01

    SUMMARY Background Multidrug-resistant tuberculosis (MDR-TB) burden estimates are based on incomplete, infrequently updated data among a limited pool of cases: notified or incident, pulmonary TB patients. Methods Using WHO data reported by 217 countries/territories in 2014, we calculated MDR-TB burdens among prevalent TB cases and compared these with estimates among incident and notified TB patients. We also compared treatment coverage across estimates. Findings Among prevalent TB patients globally in 2014, we estimate that 555,545 (95% credible bounds: 499,340–617,391) MDR-TB cases occurred. This is 85% more than the 300,000 estimated among notified cases, and 16% more than the 480,000 among incident cases. Only 20% of MDR-TB cases among prevalent—compared to 37% of MDR-TB among notified—TB patients had access to MDR-TB treatment. Applying prior estimates, only 10% of MDR-TB cases will have successful outcomes. Interpretation Estimates based on likely-to-be-diagnosed cases of MDR-TB overlook a significant proportion of morbidity, mortality, and transmission: that occur in undiagnosed, untreated, prevalent TB patients. Still likely underestimating the true disease burden, MDR-TB among patients with prevalent TB represents a closer approximation of disease burden than currently reported indicators. Progress toward elimination—or control—depends on policies guided by a more complete representation of the disease burden. PMID:28157458

  16. Experience of active tuberculosis case finding in nearly 5 million households in India.

    PubMed

    Prasad, B M; Satyanarayana, S; Chadha, S S; Das, A; Thapa, B; Mohanty, S; Pandurangan, S; Babu, E R; Tonsing, J; Sachdeva, K S

    2016-03-21

    In India, to increase tuberculosis (TB) case detection under the National Tuberculosis Programme, active case finding (ACF) was implemented by the Global Fund-supported Project Axshya, among high-risk groups in 300 districts. Between April 2013 and December 2014, 4.9 million households covering ~20 million people were visited. Of 350 047 presumptive pulmonary TB cases (cough of ⩾2 weeks) identified, 187 586 (54%) underwent sputum smear examination and 14 447 (8%) were found to be smear-positive. ACF resulted in the detection of a large number of persons with presumptive pulmonary TB and smear-positive TB. Ensuring sputum examination of all those with presumptive TB was a major challenge.

  17. Impact of activities in self-esteem of patients in a pulmonary rehabilitation program

    PubMed Central

    de Oliveira, Juliana Nascimento; Tavares, Cecilia Melo Rosa; Squassoni, Selma Denis; Machado, Nadine Cristina; Cordoni, Priscila Kessar; Bortolassi, Luciene Costa; Lapa, Mônica Silveira; Fiss, Elie

    2015-01-01

    Objective To evaluate self-esteem and self-image of respiratory diseases patients in a Pulmonary Rehabilitation Program, who participated in socialization and physical fitness activities, and of patients who participated only in physical fitness sessions. Methods A descriptive cross-sectional exploratory study. Out of a total of 60 patients analyzed, all enrolled in the Pulmonary Rehabilitation Program, 42 participated in at least one of the proposed activities, 10 did not participate in any activity and 8 were excluded (7 were discharged and 1 died). Results When the two groups were compared, despite the fact that both demonstrated low self-esteem and self-image, the difference between them was relevant (p<0.05) regarding self-esteem, indicating that those who participated in the proposed socialization activities had better self-esteem than the individuals who only did the physical fitness sessions. Regarding self-image, the difference between the groups was not relevant (p>0.05). Conclusion The Pulmonary Rehabilitation Program patients evaluated presented low self-esteem and self-image; however, those carrying out some socialization activity proposed had better self-esteem as compared to the individuals who did only the physical fitness sessions. PMID:25993068

  18. HER2 activation results in β-catenin-dependent changes in pulmonary epithelial permeability

    PubMed Central

    Vasu, Vihas T.; Thaikoottathil, Jyoti V.; Mishra, Rangnath; Shatat, Mohammad A.; Mason, Robert J.; Kern, Jeffrey A.

    2014-01-01

    The receptor tyrosine kinase human epidermal growth factor receptor-2 (HER2) is known to regulate pulmonary epithelial barrier function; however, the mechanisms behind this effect remain unidentified. We hypothesized that HER2 signaling alters the epithelial barrier through an interaction with the adherens junction (AJ) protein β-catenin, leading to dissolution of the AJ. In quiescent pulmonary epithelial cells, HER2 and β-catenin colocalized along the lateral intercellular junction. HER2 activation by the ligand neuregulin-1 was associated with tyrosine phosphorylation of β-catenin, dissociation of β-catenin from E-cadherin, and decreased E-cadherin-mediated cell adhesion. All effects were blocked with the HER2 inhibitor lapatinib. β-Catenin knockdown using shRNA significantly attenuated neuregulin-1-induced decreases in pulmonary epithelial resistance in vitro. Our data indicate that HER2 interacts with β-catenin, leading to dissolution of the AJ, decreased cell-cell adhesion, and disruption of the pulmonary epithelial barrier. PMID:25326580

  19. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension

    PubMed Central

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193

  20. Prolonged activation of IL-5–producing ILC2 causes pulmonary arterial hypertrophy

    PubMed Central

    Tsuneyama, Koichi; Kawaguchi, Makoto; Fukuoka, Junya; Kudo, Fujimi; Nakae, Susumu; Arita, Makoto; Nagai, Yoshinori; Takaki, Satoshi; Takatsu, Kiyoshi

    2017-01-01

    IL-33 is one of the critical cytokines that activates group 2 innate lymphoid cells (ILC2s) and mediates allergic reactions. Accumulating evidence suggests that IL-33 is also involved in the pathogenesis of several chronic inflammatory diseases. Previously, we generated an IL-5 reporter mouse and revealed that lung IL-5–producing ILC2s played essential roles in regulating eosinophil biology. In this study, we evaluated the consequences of IL-33 administration over a long period, and we observed significant expansion of ILC2s and eosinophils surrounding pulmonary arteries. Unexpectedly, pulmonary arteries showed severe occlusive hypertrophy that was ameliorated in IL-5– or eosinophil-deficient mice, but not in Rag2-deficient mice. This indicates that IL-5–producing ILC2s and eosinophils play pivotal roles in pulmonary arterial hypertrophy. Administration of a clinically used vasodilator was effective in reducing IL-33–induced hypertrophy and repressed the expansion of ILC2s and eosinophils. Taken together, these observations demonstrate a previously unrecognized mechanism in the development of pulmonary arterial hypertrophy and the causative roles of ILC2 in the process.

  1. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension.

    PubMed

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH.

  2. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH.

  3. Pulmonary artery location during microgravity activity: Potential impact for chest-mounted Doppler during space travel

    NASA Technical Reports Server (NTRS)

    Hadley, A. T., III; Conkin, J.; Waligora, J. M.; Horrigan, D. J., Jr.

    1984-01-01

    Doppler, or ultrasonic, monitoring for pain manifestations of decompression sickness (the bends) is accomplished by placing a sensor on the chest over the pulmonary artery and listening for bubbles. Difficulties have arisen because the technician notes that the pulmonary artery seems to move with subject movement in a one-g field and because the sensor output is influenced by only slight degrees of sensor movement. This study used two subjects and mapped the position of the pulmonary artery in one-g, microgravity, and two-g environments using ultrasound. The results showed that the pulmonary artery is fixed in location in microgravity and not affected by subject position change. The optimal position corresponded to where the Doppler signal is best heard with the subject in a supine position in a one-g environment. The impact of this result is that a proposed multiple sensor array on the chest proposed for microgravity use may not be necessary to monitor an astronaut during extravehicular activities. Instead, a single sensor of approximately 1 inch diameter and mounted in the position described above may suffice.

  4. [Plasma antithrombin III activity in patients with pulmonary thromboembolism].

    PubMed

    Vertun, B; Filipecki, S; Szczepański, M; Wawrzyńska, L; Rózycka, J

    A decreased plasma antithrombin III activity has been noted in 12 out of 20 patients. In 2 patients it was most probably congenital defect, whereas in the remaining 10 patients--acquired. The observed disorders in the activity of antithrombin III with particular reference to anticoagulant therapy have been discussed.

  5. Factors Associated with Treatment Delay among Pulmonary Tuberculosis Patients in Public and Private Health Facilities in Addis Ababa, Ethiopia

    PubMed Central

    Adenager, Getinet Shewaseged; Alemseged, Fessahaye; Asefa, Henok

    2017-01-01

    Background. Early detection and diagnosis of tuberculosis (TB) and the timely commencement of antituberculosis (anti-TB) treatment are the parts of efficient tuberculosis prevention and control program. Delay in the commencement of anti-TB treatment worsens the prognosis and increases the risk of death and the chance of transmission in the community and among health care workers. Objective. To assess tuberculosis treatment delay and associated factors among pulmonary TB patients in Addis Ababa, Ethiopia. Methods. A cross-sectional study was conducted in 10 public and 10 private health facilities that provide TB treatment. The data were collected from 425 newly registered pulmonary TB patients using pretested structured questionnaire from April to June 2012. Data were entered in EPI info version 3.5.1 and analyzed using SPSS version 16.0. Findings. The median durations of a patient, health care system, and total treatment delays were 17, 9, and 35 days, respectively. Overall 179 (42.1%), 233 (54.8%), and 262 (61.6%) of patients experienced patient delay, health care system delay, and total treatment delay, respectively. Distance more than 2.5 km from TB treatment health facility [AOR = 1.6, 95% CI (1.1–2.5)] and the presence of TB-associated stigma [AOR = 2.1, 95% CI (1.3, 3.4)] indicate higher odds of patient delay, whereas, being unemployed, patients with the hemoptysis symptom complain indicated lower odds of health care system delay [AOR = 0.41, 95% CI (0.24, 0.70)] and [AOR = 0.61 (0.39, 0.94)], respectively. Conclusions. A significant proportion of clients experienced patient and health care system delay. Thus, there is a need for designing and implementing appropriate strategies to decrease the delays. Efforts to reduce delays should give focus on integrating prevention programs such as active case detection and expanding access to TB care. PMID:28348887

  6. Tuberculosis Facts - TB and HIV/AIDS

    MedlinePlus

    Tuberculosis (TB) Facts TB and HIV/AIDS What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  7. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ≥ 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  8. Molecular and functional significance of Ca2+-activated Cl− channels in pulmonary arterial smooth muscle

    PubMed Central

    Forrest, Abigail S.; Ayon, Ramon J.; Wiwchar, Michael; Angermann, Jeff E.; Pritchard, Harry A. T.; Singer, Cherie A.; Valencik, Maria L.; Britton, Fiona; Greenwood, Iain A.

    2015-01-01

    Abstract Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca2+ levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K+ channels (e.g., Kv1.5) and increased expression and activity of voltage-dependent (Cav1.2) and voltage-independent (e.g., canonical and vanilloid transient receptor potential [TRPC and TRPV]) Ca2+ channels play an important role in the functional remodeling of pulmonary arteries in PH. This review focuses on an anion-permeable channel that is now considered a novel excitatory mechanism in the systemic and pulmonary circulations. It is permeable to Cl− and is activated by a rise in intracellular Ca2+ concentration (Ca2+-activated Cl− channel, or CaCC). The first section outlines the biophysical and pharmacological properties of the channel and ends with a description of the molecular candidate genes postulated to encode for CaCCs, with particular emphasis on the bestrophin and the newly discovered TMEM16 and anoctamin families of genes. The second section provides a review of the various sources of Ca2+ activating CaCCs, which include stimulation by mobilization from intracellular Ca2+ stores and Ca2+ entry through voltage-dependent and voltage-independent Ca2+ channels. The third and final section summarizes recent findings that suggest a potentially important role for CaCCs and the gene TMEM16A in PH. PMID:26064450

  9. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  10. Oxidant and enzymatic antioxidant status (gene expression and activity) in the brain of chickens with cold-induced pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Hassanpour, Hossein; Khalaji-Pirbalouty, Valiallah; Nasiri, Leila; Mohebbi, Abdonnaser; Bahadoran, Shahab

    2015-11-01

    To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and forebrain) in chickens with cold-induced pulmonary hypertension, the measurements of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic activity, and gene expression (for catalase, glutathione peroxidase, and superoxide dismutases) were done. There were high lipid peroxidation/protein oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary hypertensive chickens compared to control ( P < 0.05). In the hypertensive chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and hindbrain), while catalase activity was increased (forebrain and midbrain) ( P < 0.05). Glutathione peroxidase activity did not change. Relative gene expression of catalase and superoxide dismutases (1 and 2) was downregulated, while glutathione peroxidase was upregulated in the brain of the cold-induced pulmonary hypertensive chickens. Probably, these situations in the oxidant and antioxidant status of the brain especially hindbrain may change its function at cardiovascular center and sympathetic nervous system to exacerbate pulmonary hypertension.

  11. Modulation of Rac1 Activity by ADMA/DDAH Regulates Pulmonary Endothelial Barrier Function

    PubMed Central

    Torondel, Belen; Zhao, Lan; Renné, Thomas; Leiper, James M.

    2009-01-01

    Endogenously produced nitric oxide synthase inhibitor, asymmetric methylarginine (ADMA) is associated with vascular dysfunction and endothelial leakage. We studied the role of ADMA, and the enzymes metabolizing it, dimethylarginine dimethylaminohydrolases (DDAH) in the regulation of endothelial barrier function in pulmonary macrovascular and microvascular cells in vitro and in lungs of genetically modified heterozygous DDAHI knockout mice in vivo. We show that ADMA increases pulmonary endothelial permeability in vitro and in in vivo and that this effect is mediated by nitric oxide (NO) acting via protein kinase G (PKG) and independent of reactive oxygen species formation. ADMA-induced remodeling of actin cytoskeleton and intercellular adherens junctions results from a decrease in PKG-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and a subsequent down-regulation of Rac1 activity. The effects of ADMA on endothelial permeability, Rac1 activation and VASP phosphorylation are prevented by overexpression of active DDAHI and DDAHII, whereas inactive DDAH mutants have no effect. These findings demonstrate for the first time that ADMA metabolism critically determines pulmonary endothelial barrier function by modulating Rac1-mediated remodeling of the actin cytoskeleton and intercellular junctions. PMID:18923147

  12. Fatigue, anxiety and depression levels, activities of daily living of patients with chronic obstructive pulmonary disease.

    PubMed

    Karakurt, Papatya; Ünsal, Ayla

    2013-04-01

    The aim of this cross-sectional study was to determine the fatigue, anxiety and depression levels, activities of daily living of patients with chronic obstructive pulmonary disease (n = 255). It was found that there was significant difference between Visual Analogue Scale for Fatigue (VAS-F) point averages and gender, education levels, marital status and economical status of patient with chronic obstructive pulmonary disease. Among the participants in this study, 36.5% had an anxiety disorder whereas 69.0% exhibited depression. In the study, it was determined that 85.5% of those were independent in their Katz's Index of Activities of Daily Living (ADLs) and 49.4% of those were independent in their Lawton and Brody's Index of Instrumental Activities of Daily Living (IADLs). This study has shown that VAS-F, the Hospital Anxiety and Depression Scale, ADL and IADL instruments that measure the various aspects of health-related quality of living can contribute considerably to a more diversified understanding of the patients' situation with chronic obstructive pulmonary disease.

  13. Aerosol immunisation for TB: matching route of vaccination to route of infection.

    PubMed

    Manjaly Thomas, Zita-Rose; McShane, Helen

    2015-03-01

    TB remains a very significant global health burden. There is an urgent need for better tools for TB control, which include an effective vaccine. Bacillus Calmette-Guérin (BCG), the currently licensed vaccine, confers highly variable protection against pulmonary TB, the main source of TB transmission. Replacing BCG completely or boosting BCG with another vaccine are the two current strategies for TB vaccine development. Delivering a vaccine by aerosol represents a way to match the route of vaccination to the route of infection. This route of immunisation offers not only the scientific advantage of delivering the vaccine directly to the respiratory mucosa, but also practical and logistical advantages. This review summarises the state of current TB vaccine candidates in the pipeline, reviews current progress in aerosol administration of vaccines in general and evaluates the potential for TB vaccine candidates to be administered by the aerosol route.

  14. TB Screening Tests

    MedlinePlus

    ... known as: Purified Protein Derivative; PPD; Mantoux; Latent Tuberculosis Infection Test; Interferon-gamma Release Assays; IGRA; T- ... else I should know? How is it used? Tuberculosis (TB) screening tests are not used as general ...

  15. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice

    PubMed Central

    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. PMID:26272953

  16. Regulatory effect of AMP-activated protein kinase on pulmonary hypertension induced by chronic hypoxia in rats: in vivo and in vitro studies.

    PubMed

    Huang, Xiaoying; Fan, Rong; Lu, Yuanyuan; Yu, Chang; Xu, Xiaomei; Zhang, Xie; Liu, Panpan; Yan, Shuangquan; Chen, Chun; Wang, Liangxing

    2014-06-01

    Activation of AMP-activated protein kinase (AMPK) plays an important role in cardiovascular protection. It can inhibit arterial smooth muscle cell proliferation and cardiac fibroblast collagen synthesis induced by anoxia. However, the role of AMPK-dependent signalling cascades in the pulmonary vascular system is currently unknown. This study aims to determine the effects of AMPK on pulmonary hypertension and pulmonary vessel remodelling induced by hypoxia in rats using in vivo and in vitro studies. In vivo study: pulmonary hypertension, right ventricular hypertrophy and pulmonary vascular remodelling were found in hypoxic rats. Meanwhile, AMPKα1 and phosphorylated AMPKα1 were increased markedly in pulmonary arterioles and lung tissues. Mean pulmonary arterial pressure, index of right ventricular hypertrophy and parameters of pulmonary vascular remodelling, including vessel wall area/total area, density of nuclei in medial smooth muscle cells, and thickness of the medial smooth muscle cell layer were markedly suppressed by AICAR, an AMPK agonist. In vitro study: the expression of AMPKα1 and phosphorylated AMPKα1 was increased in pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions. The effects of PASMC proliferation stimulated by hypoxia were reinforced by treatment with Compound C, an AMPK inhibitor. AICAR inhibited the proliferation of PASMCs stimulated by hypoxia. These findings suggest that AMPK is involved in the formation of hypoxia-induced pulmonary hypertension and pulmonary vessel remodelling. Up-regulating AMPK can contribute to decreasing pulmonary vessel remodelling and pulmonary hypertension induced by hypoxia.

  17. Caecal perforation from TB and the Law of Laplace

    PubMed Central

    Khan, Amad N.; Khalid, Salema; Chaudhry, Mohammad Naushad; Ho, Cherrie

    2015-01-01

    A 43-year-old man presented to the hospital with haemoptysis. When worked up, his history and examination were highly suggestive of pulmonary tuberculosis (TB). He subsequently developed a massive upper gastrointestinal bleed and underwent an emergency laparotomy, which revealed a massively dilated caecum measuring ∼20 cm in diameter. The caecum had perforated due to acute decompensation of intestinal TB. Though common in developing countries, TB is rare in the UK, especially the intestinal kind. The most striking feature of this case is, however, the size of the caecal distension caused by the tubercular inflammation and subsequent perforation—something unheard of in the literature. This massive caecal distention would be explained by the Law of Laplace. In conclusion, massive distension and caecal perforation are possible consequences of intestinal TB, especially in the 48–72 h immediately after starting anti-tubercular therapy. PMID:25972412

  18. Pulmonary toxicity and metabolic activation of dauricine in CD-1 mice.

    PubMed

    Jin, Hua; Dai, Jieyu; Chen, Xiaoyan; Liu, Jia; Zhong, Dafang; Gu, Yansong; Zheng, Jiang

    2010-03-01

    Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. and has shown promising pharmacological activities with a great potential for clinic use. However, the adverse effects and toxicity of the alkaloid are unfortunately ignored. The objective of the current study was to evaluate the toxicity of dauricine in vitro and in vivo. Mice (CD-1) were treated intraperitoneally with dauricine at various doses, and sera and lung lavage fluids were collected after 24 h of treatment. No changes in serum aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen were noticed, whereas a dose-dependent increase in lactate dehydrogenase activity was observed in lung lavage fluids. Ethidium-based staining studies showed that remarkable cells lost membrane integrity in the lungs of the animals treated with dauricine at 150 mg/kg. Histopathological evaluation of lungs of mice showed that dauricine at the same dose caused significant alveolar edema and hemorrhage. Exposure to dauricine at 40 muM for 24 h resulted in up to 60% cell death in human lung cell lines BEAS-2B, WI-38, and A549. Ketoconazole showed protective effect on the pulmonary injury in mice given dauricine. A quinone methide metabolite of dauricine was identified in mouse lung microsomal incubations, and the presence of ketoconazole in the microsomal incubations suppressed the formation of the quinone methide metabolite. In conclusion, dauricine produced pulmonary injury in CD-1 mice. The pulmonary toxicity appears to depend on the metabolism of dauricine mediated by CYP3A. The electrophilic quinone methide metabolite probably plays an important role in the pulmonary toxicity induced by dauricine.

  19. [Measurement of physical activity in patients with chronic obstructive pulmonary disease].

    PubMed

    Magnussen, Helgo; Waschki, Benjamin; Watz, Henrik

    2009-04-15

    Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD.

  20. Characteristics of adults and children diagnosed with tuberculosis in Lilongwe, Malawi: findings from an integrated HIV/TB clinic

    PubMed Central

    Feldacker, C.; Tweya, H.; Keiser, O.; Weigel, R.; Kalulu, M.; Fenner, L.; Egger, M.; Manda, E.; Mwafilaso, J. B.; Kamba, C.; Phiri, S.

    2013-01-01

    Objectives To describe initial registration characteristics of adult and pediatric TB patients at a large, public, integrated TB and HIV clinic in Lilongwe, Malawi, between January 2008 – December 2010. Methods Routine data on TB patient category and TB type, stratified by HIV and ART status, were used to explore differences in proportions among TB-only, TB/HIV co-infected patients not on ART, and TB/HIV co-infected patients on ART using Chi-square tests.. Trends over time illustrate strengths and weaknesses of integrated service provision. Results Among 10,143 adults, HIV ascertainment and ART uptake were high and increased over time. The proportion of relapse was highest among those on ART (5%). The proportion of smear-positive pulmonary TB (PTB) was highest among HIV-negative TB patients (34.9%); extra-pulmonary TB (EPTB) was lowest among TB-only (16.2%). Among 338 children <15 years, EPTB and smear-positive PTB were more common among TB-only patients. Time trends showed significant increases in the proportion of adults with smear-positive PTB and the proportion of adults already on ART before starting TB treatment. However, some co-infected patients still delay ART initiation. Conclusions HIV ascertainment and ART uptake among co-infected patients is successful and improving over time. However, delays in ART initiation indicate some weakness linking TB/HIV patients into ART during TB follow-up care. Improved TB diagnostics and screening efforts, especially for pediatric patients, may help improve quality care for co-infected patients. These results may aid efforts to prioritize TB and HIV prevention, education, and treatment campaigns for specific populations. PMID:22808948

  1. Active relearning for robust supervised classification of pulmonary emphysema

    NASA Astrophysics Data System (ADS)

    Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Bartholmai, Brian J.; Robb, Richard A.

    2012-03-01

    Radiologists are adept at recognizing the appearance of lung parenchymal abnormalities in CT scans. However, the inconsistent differential diagnosis, due to subjective aggregation, mandates supervised classification. Towards optimizing Emphysema classification, we introduce a physician-in-the-loop feedback approach in order to minimize uncertainty in the selected training samples. Using multi-view inductive learning with the training samples, an ensemble of Support Vector Machine (SVM) models, each based on a specific pair-wise dissimilarity metric, was constructed in less than six seconds. In the active relearning phase, the ensemble-expert label conflicts were resolved by an expert. This just-in-time feedback with unoptimized SVMs yielded 15% increase in classification accuracy and 25% reduction in the number of support vectors. The generality of relearning was assessed in the optimized parameter space of six different classifiers across seven dissimilarity metrics. The resultant average accuracy improved to 21%. The co-operative feedback method proposed here could enhance both diagnostic and staging throughput efficiency in chest radiology practice.

  2. Decrease of U(VI) Immobilization Capability of the Facultative Anaerobic Strain Paenibacillus sp. JG-TB8 under Anoxic Conditions Due to Strongly Reduced Phosphatase Activity

    PubMed Central

    Reitz, Thomas; Rossberg, Andre; Barkleit, Astrid; Selenska-Pobell, Sonja; Merroun, Mohamed L.

    2014-01-01

    Interactions of a facultative anaerobic bacterial isolate named Paenibacillus sp. JG-TB8 with U(VI) were studied under oxic and anoxic conditions in order to assess the influence of the oxygen-dependent cell metabolism on microbial uranium mobilization and immobilization. We demonstrated that aerobically and anaerobically grown cells of Paenibacillus sp. JG-TB8 accumulate uranium from aqueous solutions under acidic conditions (pH 2 to 6), under oxic and anoxic conditions. A combination of spectroscopic and microscopic methods revealed that the speciation of U(VI) associated with the cells of the strain depend on the pH as well as on the aeration conditions. At pH 2 and pH 3, uranium was exclusively bound by organic phosphate groups provided by cellular components, independently on the aeration conditions. At higher pH values, a part (pH 4.5) or the total amount (pH 6) of the dissolved uranium was precipitated under oxic conditions in a meta-autunite-like uranyl phosphate mineral phase without supplying an additional organic phosphate substrate. In contrast to that, under anoxic conditions no mineral formation was observed at pH 4.5 and pH 6, which was clearly assigned to decreased orthophosphate release by the cells. This in turn was caused by a suppression of the indigenous phosphatase activity of the strain. The results demonstrate that changes in the metabolism of facultative anaerobic microorganisms caused by the presence or absence of oxygen can decisively influence U(VI) biomineralization. PMID:25157416

  3. Predictors of Prolonged TB Treatment in a Dutch Outpatient Setting

    PubMed Central

    Daskapan, Alper; Kosterink, Jos G. W.; van der Werf, Tjip S.; van den Hof, Susan; Alffenaar, Jan-Willem C.

    2016-01-01

    Introduction Standard treatment duration for drug-susceptible tuberculosis (TB) treatment is 6 months. Treatment duration is often extended—and for various different reasons. The aim of this study was to determine the prevalence and to assess risk factors associated with extended TB treatment. Methods A cross-sectional study was conducted. Data including demographic, clinical, radiological and microbiological information from the Netherlands TB Register (NTR) of 90 patients with smear and culture positive pulmonary TB of the region Haaglanden, The Netherlands, was eligible for analysis. Results Treatment was extended to ≥ 200 days by 46 (51%) patients. Extended TB treatment was associated with a higher frequency of symptoms, presumed to be due to adverse drug reactions (ADR; OR 2.39 95% CI: 1.01–5.69), drug-induced liver injury (DILI) (OR: 13.51; 95% CI: 1.66–109.82) and longer than 2 month smear and culture conversion rate (OR: 11.00; 95% CI: 1.24–97.96 and OR: 8.56; 95% CI: 1.53–47.96). In the multivariable logistic analysis, development of DILI emerged as the single statistically strong risk factor necessitating extension of TB treatment. Conclusion This finding will need further confirmation in a prospective study, exploring the possible mutual role of pharmacokinetic and pharmacogenetic determinants of DILI among TB patients. PMID:27832142

  4. Tuberculosis Facts - You Can Prevent TB

    MedlinePlus

    Tuberculosis (TB) Facts You Can Prevent TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination TB Facts: You Can Prevent TB What ...

  5. Tuberculosis Facts - TB Can Be Treated

    MedlinePlus

    Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Page 1 of 2 TB Facts: TB ...

  6. [Diagnosis delay of pleural and pulmonary tuberculosis].

    PubMed

    Cherif, J; Mjid, M; Ladhar, A; Toujani, S; Mokadem, S; Louzir, B; Mehiri, N; Béji, M

    2014-08-01

    Tuberculosis (TB) is still being endemic in our country. Time until management determines both evolution and prognosis of this condition. The aim of this work is to evaluate the delay in diagnosis of TB in a respiratory unit from a university hospital series. The authors conducted a cross-sectional study including patients with pulmonary TBC and/or pleural. An evaluation of time management was conducted from the beginning of symptoms and various consultations with reference to the date of hospitalization and treatment set up. One hundred patients were included (pulmonary TB: 68 cases, pleural TB 23 cases, miliary pulmonary TB: 4 cases, pulmonary TB associated with other extrathoracic locations: 5 cases). The mean time of patient delay and total delay institution were respectively 43.6, 25.7 and 69.3 days. Variables responsible for long delays were: number of consultations more than 3 before hospitalization, empirical antibiotic therapy, of a regional hospital first consultation and the presence of extra-respiratory impairment. The patient delay was considered long. A reorganization of the TB control program, in particular by partial decentralization of care and health education is imperative in order to improve the quality of tuberculosis management in our country.

  7. IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells.

    PubMed

    Bansal, Geetanjali; Das, Dividutta; Hsieh, Cheng-Ying; Wang, Yi-Hsuan; Gilmore, Brent A; Wong, Chi-Ming; Suzuki, Yuichiro J

    2013-12-01

    Reactive oxygen species (ROS) mediate cell-signaling processes in response to various ligands and play important roles in the pathogenesis of cardiovascular diseases. The present study reports that interleukin-22 (IL-22) elicits signal transduction in vascular smooth muscle cells (SMCs) through a ROS-dependent mechanism. We find that pulmonary artery SMCs express IL-22 receptor alpha 1 and that IL-22 activates STAT3 through this receptor. IL-22-induced signaling is found to be mediated by NADPH oxidase, as indicated by the observations that the inhibition and siRNA knock-down of this enzyme inhibit IL-22 signaling. IL-22 triggers the oxidative modifications of proteins through protein carbonylation and protein glutathionylation. Mass spectrometry identified some proteins that are carbonylated in response to IL-22 stimulation, including α-enolase, heat shock cognate 71kDa protein, mitochondrial 60kDa heat shock protein, and cytoplasmic 2 actin and determined that α-tubulin is glutathionylated. Protein glutathionylation and STAT3 phosphorylation are enhanced by the siRNA knock-down of glutaredoxin, while IL-22-mediated STAT3 phosphorylation is suppressed by knocking down thioredoxin interacting protein, an inhibitor of thioredoxin. IL-22 is also found to promote the growth of SMCs via NADPH oxidase. In rats, pulmonary hypertension is found to be associated with increased smooth muscle IL-22 expression. These results show that IL-22 promotes the growth of pulmonary vascular SMCs via a signaling mechanism that involves NADPH oxidase-dependent oxidation.

  8. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

    PubMed

    François, Antoine; Gombault, Aurélie; Villeret, Bérengère; Alsaleh, Ghada; Fanny, Manoussa; Gasse, Paméla; Adam, Sylvain Marchand; Crestani, Bruno; Sibilia, Jean; Schneider, Pascal; Bahram, Seiamak; Quesniaux, Valérie; Ryffel, Bernhard; Wachsmann, Dominique; Gottenberg, Jacques-Eric; Couillin, Isabelle

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A.

  9. Basic fibroblast growth factor activates β-catenin/RhoA signaling in pulmonary fibroblasts with chronic obstructive pulmonary disease in rats.

    PubMed

    Ge, Zhengxing; Li, Bo; Zhou, Xun; Yang, Yi; Zhang, Jun

    2016-12-01

    Chronic obstructive pulmonary disease (COPD) is featured by aberrant extracellular matrix (ECM) deposition. Trigger of the β-catenin/RhoA pathway has been involved in aberrant ECM deposition in several diseases. We investigated WNT signaling activation in primary pulmonary fibroblasts of rats with and without COPD and the function of WNT signaling in pulmonary fibroblast. We evaluated the expression of WNT signaling and the role of β-catenin, using MRC-5 fibroblasts and primary lung fibroblasts of rats with and without COPD. Lung fibroblasts highly expressed mRNA of genes associated with WNT signaling. Treatment of MRC-5 fibroblasts using basic fibroblast growth factor (bFGF), a composition of the mucus in COPD patients, enhanced β-catenin, Wnt5a and RhoA expression. The expression in β-catenin, Wnt5a and RhoA induced by bFGF was higher in fibroblasts of rats with COPD than without COPD, whereas the basal expression was similar. bFGF also activated transcriptionally active and increased total β-catenin protein expression. Moreover, bFGF enhanced the expression of α-sm-actin and fibronectin, which was abrogated by β-catenin, Wnt5a and RhoA-specific adenovirus siRNA. The induction of active β-catenin and then fibronectin turnover in response to bFGF were markedly increased in pulmonary fibroblasts from rat with COPD. β-Catenin/RhoA pathway results in ECM deposition in lung fibroblasts and myofibroblasts differentiation. β-catenin/RhoA signaling induced by bFGF is promoted in lung fibroblasts from rats with COPD. The study indicated a crucial role of the WNT signaling in mediating fibroblast morphology and function in COPD.

  10. Luminescence, Energy Transfer and Tunable Color of Ce3+- and Tb3+-Activated Na3Gd(BO3)2 Phosphors

    NASA Astrophysics Data System (ADS)

    Zhang, Xinguo; Pan, Jialiang; Mo, Fuwang

    2017-02-01

    A series of blue Na3Gd(BO3)2:Ce3+ and blue-to-green color-tunable Na3Gd (BO3)2:Ce3+,Tb3+ phosphors were synthesized by the solid-state method. The luminescence, concentration quenching and energy transfer (ET) process of Na3Gd(BO3)2:Ce3+,Tb3+ were investigated. Both Ce3+ and Tb3+ occupy the Gd3+ site in the Na3Gd(BO3)2 host. Na3Gd(BO3)2:Ce3+ exhibits strong ultraviolet absorption and broadband blue emission. The Ce3+ sensitization effect on Tb3+ has been verified by the variation of PL/PLE spectra, the Ce3+ decay lifetimes and the energy transfer efficiency of Na3Gd(BO3)2:Ce3+,Tb3+ phosphors. The maximum Ce3+-Tb3+ ET efficiency has been calculated to be 95%. The emitting color of the obtained phosphors can be modulated from blue (0.179, 0.204) through bluish-green (0.271, 0.391) to green (0.349, 0.551) by properly changing the ratio of Ce3+/Tb3+.

  11. TB in Vulnerable Populations

    PubMed Central

    Ugarte-Gil, César; Caro, Godofredo; Aylas, Rula; Castro, César; Lema, Claudia

    2016-01-01

    Abstract This article analyzes the factors associated with vulnerability of the Ashaninka, the most populous indigenous Peruvian Amazonian people, to tuberculosis (TB). By applying a human rights-based analytical framework that assesses public policy against human rights standards and principles, and by offering a step-by-step framework for a full assessment of compliance, it provides evidence of the relationship between the incidence of TB among the Ashaninka and Peru’s poor level of compliance with its human rights obligations. The article argues that one of the main reasons for the historical vulnerability of the Ashaninka to diseases such as TB is a lack of political will on the part of the national government to increase public health spending, ensure that resources reach the most vulnerable population, and adopt and invest in a culturally appropriate health system. PMID:27780999

  12. Photoluminescence properties of rare earths (Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+}) activated NaInW{sub 2}O{sub 8} wolframite host lattice

    SciTech Connect

    Asiri Naidu, S.; Boudin, S.; Varadaraju, U.V.; Raveau, B.

    2012-01-15

    The photoluminescence (PL) studies on NaIn{sub 1-x}RE{sub x}W{sub 2}O{sub 8}, with RE=Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+} phases have shown that the relative contribution of the host lattice and of the intra-f-f emission of the activators to the PL varies with the nature of the rare earth cation. In the case of Dy{sup 3+} and Tm{sup 3+} activators, with yellow and blue emission, respectively, the energy transfer from host to the activator plays a major role. In contrast for Eu{sup 3+}, with intense red emission, the host absorption is less pronounced and the intra-f-f transitions of the Eu{sup 3+} ions play a major role, whereas for Tb{sup 3+} intra-f-f transitions are only observed, giving rise to green emission. - Graphical abstract: NaInW{sub 2}O{sub 8} double tungstate doped with Eu{sup 3+}, Dy{sup 3+}, Tb{sup 3+}and Tm{sup 3+} shows characteristic emission of intense red for Eu{sup 3+}, yellow for Dy{sup 3+}, green for Tb{sup 3+} and blue for Tm{sup 3+}. Highlights: Black-Right-Pointing-Pointer Characteristic emissions of rare earths (Eu{sup 3+}, Tb{sup 3+}, Dy{sup 3+} and Tm{sup 3+}) are observed NaInW{sub 2}O{sub 8} wolframite. Black-Right-Pointing-Pointer Energy transfer from host to the activators (Eu{sup 3+} Dy{sup 3+} Tm{sup 3+} is observed. Black-Right-Pointing-Pointer PL properties of rare earth ions depend on minor structural variations in the host lattice.

  13. An experimental assessment of the influence of exercise versus social implementation intentions on physical activity during and following pulmonary rehabilitation.

    PubMed

    Rodgers, Wendy M; Selzler, Anne-Marie; Haennel, Robert G; Holm, Siri; Wong, Eric Y L; Stickland, Michael K

    2014-06-01

    Techniques to increase physical activity among pulmonary rehabilitation patients outside of the rehabilitation context are warranted. Implementation intentions are a strategy used to initiate goal-directed behaviour, and have been found to be useful in other populations. This study compared the long-term effects of exercise and social implementation intentions interventions on objectively measured physical activity in 40 pulmonary rehabilitation patients randomly assigned to condition. Repeated measures ANOVAs found that those in the exercise implementation intentions group took more steps (p = .007) at the end of pulmonary rehabilitation than those in the social implementation intentions group. Improvements attained by the exercise group during the intervention were not maintained 6-months following rehabilitation. Implementation intentions targeting physical activity appear to have positive short term effects on physical activity, although the long term effects are less consistent. This may be due in part to methods used to assess physical activity behaviour.

  14. Lung Volume Reduction Surgery and Pulmonary Rehabilitation Improve Exercise Capacity and Reduce Dyspnea During Functional Activities in People with Emphysema

    PubMed Central

    2009-01-01

    Purpose: The purpose of this study was to examine the therapeutic effects of lung volume reduction surgery (LVRS) and pulmonary rehabilitation on levels of dyspnea during functional activities in patients with diffuse emphysema. Methods: Fifteen subjects who had undergone LVRS participated in this study. A visual analog scale (VAS) Activity Dyspnea Scales (VADS) measurement tool developed for this study was determined reliable in 10 subjects. The VADS was used to assess changes in dyspnea with functional activity in 10 subjects prior to and following the interventions of LVRS and pulmonary rehabilitation. Results: Results of this study indicate that LVRS followed by pulmonary rehabilitation significantly reduces levels of dyspnea during functional activities. Conclusion: The VADS developed for this study is a valid and reliable method of assessing changes in levels of dyspnea during functional activities in the LVRS population. PMID:20467532

  15. Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.

    PubMed

    Ourique, Aline Ferreira; Chaves, Paula Dos Santos; Souto, Gabriele Dadalt; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

    2014-12-18

    Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

  16. Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9

    PubMed Central

    Wang, Yiran; Chen, Ali; Chen, Mayun; Yao, Dan; Xu, Xiaomei; Wang, Liangxing

    2016-01-01

    Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway. PMID:27688788

  17. Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9.

    PubMed

    Yan, Shuangquan; Wang, Yiran; Liu, Panpan; Chen, Ali; Chen, Mayun; Yao, Dan; Xu, Xiaomei; Wang, Liangxing; Huang, Xiaoying

    2016-01-01

    Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

  18. Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9

    PubMed Central

    Ordonez, Alvaro A.; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J.; Klunk, Mariah H.; Mollura, Daniel J.; Nuermberger, Eric L.

    2016-01-01

    ABSTRACT Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis. Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ. A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

  19. Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis.

    PubMed

    Sun, Zhaorui; Wang, Cong; Shi, Chaowen; Sun, Fangfang; Xu, Xiaomeng; Qian, Weiping; Nie, Shinan; Han, Xiaodong

    2014-05-01

    Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.

  20. p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis

    PubMed Central

    Wang, Wei; Liu, Haijun; Dai, Xiaoniu; Fang, Shencun; Wang, Xingang; Zhang, Yingming; Yao, Honghong; Zhang, Xilong; Chao, Jie

    2015-01-01

    Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear. Here, to elucidate the role of p53 in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Experiments using primary cultured adult human pulmonary fibroblasts led to the following results: 1) SiO2 treatment resulted in a rapid and sustained increase in p53 and PUMA protein levels; 2) the MAPK and PI3K pathways were involved in the SiO2-induced alteration of p53 and PUMA expression; and 3) RNA interference targeting p53 and PUMA prevented the SiO2-induced increases in fibroblast activation and migration. Our study elucidated a link between SiO2-induced p53/PUMA expression in fibroblasts and cell migration, thereby providing novel insight into the potential use of p53/PUMA in the development of novel therapeutic strategies for silicosis treatment. PMID:26576741

  1. Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

    ERIC Educational Resources Information Center

    Migrant Clinicians Network, Inc., Austin, TX.

    A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…

  2. TB in Children in the United States

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

  3. Role of B Cells in Mucosal Vaccine-Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis.

    PubMed

    Khera, Amandeep K; Afkhami, Sam; Lai, Rocky; Jeyanathan, Mangalakumari; Zganiacz, Anna; Mandur, Talveer; Hammill, Joni; Damjanovic, Daniela; Xing, Zhou

    2015-09-15

    Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and lung interstitium of genetic B cell-deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and lung interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell-competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis.

  4. A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents.

    PubMed

    Lin, Yu-Jung; Lin, Ruei-Lung; Ruan, Ting; Khosravi, Mehdi; Lee, Lu-Yuan

    2015-02-01

    Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are coexpressed in vagal pulmonary C-fiber sensory nerves. Because both these receptors are sensitive to a number of endogenous inflammatory mediators, it is conceivable that they can be activated simultaneously during airway inflammation. This study aimed to determine whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. In anesthetized, spontaneously breathing rats, the reflex-mediated apneic response to intravenous injection of a combined dose of allyl isothiocyanate (AITC, a TRPA1 activator) and capsaicin (Cap, a TRPV1 activator) was ∼202% greater than the mathematical sum of the responses to AITC and Cap when they were administered individually. Similar results were also observed in anesthetized mice. In addition, the synergistic effect was clearly demonstrated when the afferent activity of single vagal pulmonary C-fiber afferents were recorded in anesthetized, artificially ventilated rats; C-fiber responses to AITC, Cap and AITC + Cap (in combination) were 0.6 ± 0.1, 0.8 ± 0.1, and 4.8 ± 0.6 impulses/s (n = 24), respectively. This synergism was absent when either AITC or Cap was replaced by other chemical activators of pulmonary C-fiber afferents. The pronounced potentiating effect was further demonstrated in isolated vagal pulmonary sensory neurons using the Ca(2+) imaging technique. In summary, this study showed a distinct positive interaction between TRPA1 and TRPV1 when they were activated simultaneously in pulmonary C-fiber sensory nerves.

  5. Multidrug-Resistant TB

    PubMed Central

    Cox, Helen; Coomans, Fons

    2016-01-01

    Abstract The right to enjoy the benefits of scientific progress (REBSP) is a little-known but potentially valuable right that can contribute to rights-based approaches to addressing multidrug-resistant TB (MDR-TB). We argue that better understanding of the REBSP may help to advance legal and civil society action for health rights. While the REBSP does not provide an individual entitlement to have a new drug developed for MDR-TB, it sets up entitlements to expect a state to establish a legislative and policy framework aimed at developing scientific capacity to address the most important health issues and at disseminating the outcomes of scientific research. By making scientific findings available and accessible, people can be enabled to claim the use of science for social benefits. Inasmuch as the market fails to address neglected diseases such as MDR-TB, the REBSP provides a potential counterbalance to frame a positive obligation on states to both marshal their own resources and to coordinate the actions of multiple other actors towards this goal, including non-state actors. While the latter do not hold the same level of accountability as states, the REBSP can still enable the recognition of obligations at a level of “soft law” responsibilities. PMID:27780997

  6. Relevance of latent TB infection in areas of high TB prevalence.

    PubMed

    Sharma, Surendra K; Mohanan, Sandeep; Sharma, Abhishek

    2012-09-01

    About one-third of the world population has latent TB infection (LTBI), the majority of which is distributed in 22 high-burden countries. Early diagnosis and treatment of active TB remains the top priority in resource-poor countries with high TB prevalence. Notwithstanding, because LTBI contributes significantly to the pool of active TB cases later on, its diagnosis and treatment is essential, especially in high-risk groups. The lack of a gold standard and several limitations of currently available tools, namely the tuberculin skin test and interferon-γ release assays, are major constraints for LTBI diagnosis. In areas with high TB prevalence, interferon-γ release assays have not shown superiority over the conventional tuberculin skin test and are yet to be systematically studied. Decisions regarding LTBI treatment with isoniazid preventive therapy should be made, keeping in mind the high prevalence of isoniazid resistance in these settings. Although efforts to shorten the LTBI treatment duration are encouraging, most trials have focused on adherence and toxicity. Future trials on short-duration regimens in high-burden settings should address drug efficacy issues as well. LTBI management, therefore, should comprise a targeted screening approach and individualization of LTBI treatment protocols. In addition, efforts should focus on airborne infection control measures in high-burden countries. A high prevalence of drug-resistant TB, the HIV epidemic, and delays in the diagnosis of active TB cases are other major concerns in areas of high TB prevalence. There is ample space for further research in these countries, whose outcomes may strengthen future national guidelines.

  7. Wavelength dependence of Verdet constant of Tb3+:Y2O3 ceramics

    NASA Astrophysics Data System (ADS)

    Snetkov, I. L.; Permin, D. A.; Balabanov, S. S.; Palashov, O. V.

    2016-04-01

    Samples of the magneto-active material—Tb3+:Y2O3 ceramics with Tb3+ ion concentrations of 10%, 20%, 30%, and 100% (Tb2O3)—were prepared and studied. The wavelength dependence of Verdet constant in the 380 nm-1750 nm range was approximated for all investigated ceramic samples and was predicted for a pure Tb2O3 material. Tb2O3 ceramics demonstrates a more than three times higher Verdet constant in comparison with terbium gallium garnet crystal or ceramics. The linear dependence of the Verdet constant on Tb3+ ion concentration in the Tb3+:Y2O3 ceramics was demonstrated. The obtained data will be useful for fabricating magneto-optical elements of Faraday devices based on Tb3+:Y2O3 with arbitrary Tb3+ ion concentration operating at room temperature in the wavelength range of 380 nm-1750 nm.

  8. TB & HIV: the deadly intersection.

    PubMed

    MacDougall, D S

    1999-05-01

    About 2 billion people worldwide are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is the leading cause of premature death in less industrialized countries, and 8 million more people become infected every year. The World Health Organization (WHO) declared TB a global emergency in 1993 and launched a series of prevention and vaccination programs. In spite of effective drug therapy and a vaccine, tuberculosis remains a major public health problem. The TB and HIV epidemics are closely intertwined, and the risk of TB disease progression is 100 times greater in HIV-positive individuals. TB is the leading cause of death among HIV-infected people worldwide, and virologic evidence suggests that the host immune response to TB may enhance HIV replication and accelerate the progression of HIV infection. The interaction between the two diseases was the subject of a conference called TB & HIV: Applying Advances to the Clinic, Public Health, and the World. Charts and tables show reported TB cases in the U.S., trends in TB cases among foreign-born persons in the U.S., and the country of origin for foreign-born persons with TB in the U.S. Several poster sessions from the conference are summarized. Strategies for dealing with the TB epidemic are outlined.

  9. Preparation and spectroscopic properties of rare-earth (RE) (RE = Sm, Eu, Tb, Dy, Tm)-activated K{sub 2}LnZr(PO{sub 4}){sub 3} (Ln = Y, La, Gd and Lu) phosphate in vacuum ultraviolet region

    SciTech Connect

    Zhang, Zhi-Jun; Lin, Xiao; Zhao, Jing-Tai; Zhang, Guo-Bin

    2013-02-15

    Graphical abstract: Display Omitted Highlights: ► We report the VUV spectroscopic properties of rare-earth ions in K{sub 2}LnZr(PO{sub 4}){sub 3}. ► The O{sup 2−}-Eu{sup 3+} charge transfer bands at about 220 nm have been observed. ► The 4f–5d spin-allowed and spin-forbidden transitions of Tb{sup 3+} have been observed. ► There is energy transfer between the host and rare-earth activators. -- Abstract: Rare earth (RE = Sm, Eu, Tb, Dy and Tm)-activated K{sub 2}LnZr(PO{sub 4}){sub 3} (Ln = Y, La, Gd and Lu) have been synthesized by solid-state reaction method, and their vacuum ultraviolet (VUV) excitation luminescent characteristics have been investigated. The band in the wavelength range of 130–157 nm and the other one range from 155 to 216 nm with the maximum at about 187 nm in the VUV excitation spectra of these compounds are attributed to the host lattice absorption and O–Zr charge transfer transition, respectively. The charge transfer bands (CTB) of O{sup 2−}-Sm{sup 3+}, O{sup 2−}-Dy{sup 3+} and O{sup 2−}-Tm{sup 3+}, in Sm{sup 3+}, Dy{sup 3+} and Tm{sup 3+}-activated samples, have not been obviously observed probably because the 2p electrons of oxygen are tightly bound to the zirconium ion in the host lattice. For Eu{sup 3+}-activated samples, the relatively weak O{sup 2−}-Eu{sup 3+} CTB at about 220 nm is observed. And for Tb{sup 3+}-activated samples, the bands at 223 and 258 nm are related to the 4f-5d spin-allowed and spin-forbidden transitions of Tb{sup 3+}, respectively. It is observed that there is energy transfer between the host lattice and the luminescent activators (e.g. Eu{sup 3+}, Tb{sup 3+}). From the standpoint of luminescent efficiency, color purity and chemical stability, K{sub 2}GdZr(PO{sub 4}){sub 3}:Sm{sup 3+}, Eu{sup 3+}, Tb{sup 3+} are attractive candidates for novel yellow, red, green-emitting PDP phosphors.

  10. A novel preterm respiratory mechanics active simulator to test the performances of neonatal pulmonary ventilators

    NASA Astrophysics Data System (ADS)

    Cappa, Paolo; Sciuto, Salvatore Andrea; Silvestri, Sergio

    2002-06-01

    A patient active simulator is proposed which is capable of reproducing values of the parameters of pulmonary mechanics of healthy newborns and preterm pathological infants. The implemented prototype is able to: (a) let the operator choose the respiratory pattern, times of apnea, episodes of cough, sobs, etc., (b) continuously regulate and control the parameters characterizing the pulmonary system; and, finally, (c) reproduce the attempt of breathing of a preterm infant. Taking into account both the limitation due to the chosen application field and the preliminary autocalibration phase automatically carried out by the proposed device, accuracy and reliability on the order of 1% is estimated. The previously indicated value has to be considered satisfactory in light of the field of application and the small values of the simulated parameters. Finally, the achieved metrological characteristics allow the described neonatal simulator to be adopted as a reference device to test performances of neonatal ventilators and, more specifically, to measure the time elapsed between the occurrence of a potentially dangerous condition to the patient and the activation of the corresponding alarm of the tested ventilator.

  11. Plutonium behavior after pulmonary administration according to solubility properties, and consequences on alveolar macrophage activation.

    PubMed

    Van der Meeren, Anne; Gremy, Olivier; Renault, Daniel; Miroux, Amandine; Bruel, Sylvie; Griffiths, Nina; Tourdes, Françoise

    2012-01-01

    The physico-chemical form in which plutonium enters the body influences the lung distribution and the transfer rate from lungs to blood. In the present study, we evaluated the early lung damage and macrophage activation after pulmonary contamination of plutonium of various preparation modes which produce different solubility and distribution patterns. Whatever the solubility properties of the contaminant, macrophages represent a major retention compartment in lungs, with 42 to 67% of the activity from broncho-alveolar lavages being associated with macrophages 14 days post-contamination. Lung changes were observed 2 and 6 weeks post-contamination, showing inflammatory lesions and accumulation of activated macrophages (CD68 positive) in plutonium-contaminated rats, although no increased proliferation of pneumocytes II (TTF-1 positive cells) was found. In addition, acid phosphatase activity in macrophages from contaminated rats was enhanced 2 weeks post-contamination as compared to sham groups, as well as inflammatory mediator levels (TNF-α, MCP-1, MIP-2 and CINC-1) in macrophage culture supernatants. Correlating with the decrease in activity remaining in macrophages after plutonium contamination, inflammatory mediator production returned to basal levels 6 weeks post-exposure. The production of chemokines by macrophages was evaluated after contamination with Pu of increasing solubility. No correlation was found between the solubility properties of Pu and the activation level of macrophages. In summary, our data indicate that, despite the higher solubility of plutonium citrate or nitrate as compared to preformed colloids or oxides, macrophages remain the main lung target after plutonium contamination and may participate in the early pulmonary damage.

  12. Massive Pulmonary Embolism: Treatment with Thrombus Fragmentation and Local Fibrinolysis with Recombinant Human-Tissue Plasminogen Activator

    SciTech Connect

    Stock, Klaus Wilhelm; Jacob, Augustinus Ludwig; Schnabel, Karl Jakob; Bongartz, Georg; Steinbrich, Wolfgang

    1997-09-15

    Purpose: To report the results of thrombus fragmentation in combination with local fibrinolysis using recombinant human-tissue plasminogen activator (rtPA) in patients with massive pulmonary embolism. Methods: Five patients with massive pulmonary embolism were treated with thrombus fragmentation followed by intrapulmonary injection of rtPA. Clot fragmentation was performed with a guidewire, angiographic catheter, and balloon catheter. Three patients had undergone recent surgery; one of them received a reduced dosage of rtPA. Results: All patients survived and showed clinical improvement with a resultant significant (p < 0.05) decrease in the pulmonary blood pressure (mean systolic pulmonary blood pressure before treatment, 49 mmHg; 4 hr after treatment, 28 mmHg). Angiographic follow-up in three patients revealed a decrease in thrombus material and an increase in pulmonary perfusion. Two patients developed retroperitoneal hematomas requiring transfusion. Conclusion: Clot fragmentation and local fibrinolysis with rtPA was an effective therapy for massive pulmonary embolism. Bleeding at the puncture site was a frequent complication.

  13. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Pulmonary tuberculosis... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in... connection for pulmonary tuberculosis. When under consideration, all available service department films...

  14. Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis.

    PubMed

    Dorhoi, Anca; Kaufmann, Stefan H E

    2016-03-01

    Heightened morbidity and mortality in pulmonary tuberculosis (TB) are consequences of complex disease processes triggered by the causative agent, Mycobacterium tuberculosis (Mtb). Mtb modulates inflammation at distinct stages of its intracellular life. Recognition and phagocytosis, replication in phagosomes and cytosol escape induce tightly regulated release of cytokines [including interleukin (IL)-1, tumor necrosis factor (TNF), IL-10], chemokines, lipid mediators, and type I interferons (IFN-I). Mtb occupies various lung lesions at sites of pathology. Bacteria are barely detectable at foci of lipid pneumonia or in perivascular/bronchiolar cuffs. However, abundant organisms are evident in caseating granulomas and at the cavity wall. Such lesions follow polar trajectories towards fibrosis, encapsulation and mineralization or liquefaction, extensive matrix destruction, and tissue injury. The outcome is determined by immune factors acting in concert. Gradients of cytokines and chemokines (CCR2, CXCR2, CXCR3/CXCR5 agonists; TNF/IL-10, IL-1/IFN-I), expression of activation/death markers on immune cells (TNF receptor 1, PD-1, IL-27 receptor) or abundance of enzymes [arginase-1, matrix metalloprotease (MMP)-1, MMP-8, MMP-9] drive genesis and progression of lesions. Distinct lesions coexist such that inflammation in TB encompasses a spectrum of tissue changes. A better understanding of the multidimensionality of immunopathology in TB will inform novel therapies against this pulmonary disease.

  15. Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases

    PubMed Central

    Qian, Feng; Deng, Jing; Wang, Gang; Ye, Richard D.; Christman, John W.

    2016-01-01

    Mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2) is exclusively regulated by p38 MAPK in vivo. Upon activation of p38 MAPK, MK2 binds with p38 MAPK, leading to phosphorylation of TTP, Hsp27, Akt and Cdc25 that are involved in regulation of various essential cellular functions. In this review, we discuss current knowledge about molecular mechanisms of MK2 in regulation of TNF-α production, NADPH oxidase activation, neutrophil migration, and DNA-damage-induced cell cycle arrest which are involved in the molecular pathogenesis of acute lung injury, pulmonary fibrosis, and non-small-cell lung cancer. Collectively current and emerging new information indicate that developing MK2 inhibitors and blocking MK2-mediated signal pathways is a potential therapeutic strategy for treatment of inflammatory and fibrotic lung diseases and lung cancer. PMID:26119506

  16. Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells

    SciTech Connect

    Not Available

    1986-01-05

    The effects of bacterial lipopolysaccharide (endotoxin) on the fibrinolytic activity of bovine pulmonary artery endothelial cells were examined. Endotoxin suppressed the net fibrinolytic activity of cell extracts and conditioned media in a dose-dependent manner. The effects of endotoxin required at least 6 h for expression. Cell extracts and conditioned media contained a 44-kDa urokinase-like plasminogen activator. Media also contained multiple plasminogen activators with molecular masses of 65-75 and 80-100 kDa. Plasminogen activators in extracts and media were unchanged by treatment of cells with endotoxin. Diisopropyl fluorophosphate (DFP)-abolished fibrinolytic activity of extracts and conditioned media. DFP-treated samples from endotoxin-treated but not untreated cells inhibited urokinase and tissue plasminogen activator, but not plasmin. Inhibitory activity was lost by incubation at pH 3 or heating to 56/sup 0/C for 10 min. These treatments did not affect inhibitory activity of fetal bovine serum. Incubation of /sup 125/I-urokinase with DFP-treated medium from endotoxin-treated cells produced an inactive complex with an apparent molecular mass of 80-85 kDa.

  17. Tunable color temperature solid state white light source using flux grown phosphor crystals of Eu3+, Dy3+ and Tb3+ activated calcium sodium molybdenum oxide

    NASA Astrophysics Data System (ADS)

    Khanna, A.; Dutta, P. S.

    2014-11-01

    Solid state light sources with dynamically tunable color temperature in the range of 3000-6000 K with chromaticity coordinates lying on the Planckian black body curve has been designed using mixtures of narrow emissions at 615 nm, 575 nm and 550 nm. These respective emissions lines were generated by individual phosphor crystals of trivalent rare earth (RE3+) species, europium (Eu3+), dysprosium (Dy3+) and terbium (Tb3+) activated calcium sodium molybdenum oxide (Ca1-2xNaxMoO4:RE3+x), when excited by near-ultra-violet (NUV) light emitting diode (LED) with emission wavelength of 380 nm. Highly luminescent crystals of these compounds have been grown from molten solutions (flux) of molybdenum (VI) oxide. The flux grown crystals exhibit emission intensity 2-4 times more than phosphor powders of the same compounds synthesized by traditional solid-state reactions. An optimum flux to solute ratio of 2.5 and solute dissolution temperature of 1100 °C resulted in the largest size crystals.

  18. The role of bronchoscopy in the diagnosis and management of pediatric pulmonary tuberculosis.

    PubMed

    Goussard, Pierre; Gie, Robert

    2014-02-01

    Pulmonary tuberculosis (TB) is the commonest clinical form of childhood TB occurring in approximately 80% of cases. Traditionally, bronchoscopy in pediatric TB suspects was used to collect specimens for mycobacterial culture using especially bronchoalveolar lavage. New data have described the role of bronchoscopy as a more comprehensive instrument for the diagnosis and management of pulmonary TB in children. Flexible bronchoscopy is an important intervention to evaluated airways disease, collect samples for culture, relieve critical threatening airway obstruction and aid in the management of complicated pulmonary TB disease in children. Airway involvement in children suspected of pulmonary TB has been described in 41-63% of cases. The commonest airways involved are bronchus intermedius, left main bronchus and the trachea. Bronchoscopy is safe in children with severe airway obstruction. As bronchoscope images improve, the working channel size increases new applications for bronchoscopy will be developed making them more applicable in small children.

  19. TB or not TB?: a case of isolated testicular TB with scrotal involvement.

    PubMed

    Bhargava, A; Davenport, C; Gibbons, N; McConkey, S

    2009-06-01

    Despite the genitourinary tract being the most common site affected by extrapulmonary TB, isolated testicular TB remains a rare clinical entity. In patients with co-morbidities such as hepatic impairment, treatment proves a challenge, as first-line hepatotoxic pharmaceuticals are contraindicated. Here, we report a case of isolated testicular TB with scrotal involvement, on a background of hepatic dysfunction.

  20. The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A.; Hopkinson, Nicholas S.; Polkey, Michael I.; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I.; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A.; Karlsson, Niklas

    2015-01-01

    No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity. Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. PMID:26022965

  1. The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease.

    PubMed

    Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A; Hopkinson, Nicholas S; Polkey, Michael I; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A; Karlsson, Niklas; Garcia-Aymerich, Judith

    2015-10-01

    No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.

  2. Pulmonary edema

    MedlinePlus

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  3. PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis

    PubMed Central

    Shen, Lei; Gao, Yan; Liu, Yuanyuan; Zhang, Bingyan; Liu, Qianqian; Wu, Jing; Fan, Lin; Ou, Qinfang; Zhang, Wenhong; Shao, Lingyun

    2016-01-01

    The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN-γ-secreting T-cell proportion. CD4+ T-cell proliferation and macrophage functions were investigated in the presence or absence of PD-1/PD-L pathway blockade. Proportions of both PD-1+CD4+ and PD-L1+CD4+ T cells in ATB patients were more significantly increased than in the HC group (P = 0.0112 and P = 0.0141, respectively). The expressions of PD-1, PD-L1, and PD-L2 on CD14+ monocytes in ATB patients were much higher than those in the HC group (P = 0.0016, P = 0.0001, and P = 0.0088, respectively). Blockade of PD-1 could significantly enhance CD4+ T-cell proliferation (P = 0.0433). Phagocytosis and intracellular killing activity of macrophages increased significantly with PD-1/PD-L pathway blockade. In conclusion, the PD-1/PD-L pathway inhibits not only M.tb-specific CD4+ T-cell-mediated immunity but also innate immunity. PMID:27924827

  4. Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis

    PubMed Central

    Davila, Sonia; Hibberd, Martin L.; Hari Dass, Ranjeeta; Wong, Hazel E. E.; Sahiratmadja, Edhyana; Bonnard, Carine; Alisjahbana, Bachti; Szeszko, Jeffrey S.; Balabanova, Yanina; Drobniewski, Francis; van Crevel, Reinout; van de Vosse, Esther; Nejentsev, Sergey; Ottenhoff, Tom H. M.; Seielstad, Mark

    2008-01-01

    Despite high rates of exposure, only 5–10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2–2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02–1.48). Combined evidence for association is P = 1.2×10−3–6×10−4. In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36×10−5), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations. PMID:18927625

  5. Asymmetric dimethylarginine does not inhibit arginase activity and is pro-proliferative in pulmonary endothelial cells.

    PubMed

    Chen, Bernadette; Strauch, Krista; Jin, Yi; Cui, Hongmei; Nelin, Leif D; Chicoine, Louis G

    2014-07-01

    Asymmetric dimethylarginine (ADMA) is an endogenously produced nitric oxide synthase (NOS) inhibitor. L-Arginine can be metabolised by NOS and arginase, and arginase is the first step in polyamine production necessary for cellular proliferation. We tested the hypothesis that ADMA would inhibit NOS but not arginase activity and that this pattern of inhibition would result in greater L-arginine bioavailability to arginase, thereby increasing viable cell number. Bovine arginase was used in in vitro activity assays with various concentrations of substrate (L-arginine, ADMA, N(G) -monomethyl-L-arginine (L-NMMA) and N(G) -nitro-L-arginine methyl ester (L-NAME)). Only L-arginine resulted in measurable urea production (Km = 6.9 ± 0.8 mmol/L; Vmax = 6.6 ± 0.3 μmol/mg protein per min). We then incubated bovine arginase with increasing concentrations of ADMA, L-NMMA and L-NAME in the presence of 1 mmol/L l-arginine and found no effect of any of the tested compounds on arginase activity. Using bovine pulmonary arterial endothelial cells (bPAEC) we determined the effects of ADMA on nitric oxide (NO) and urea production and found significantly lower NO production and greater urea production (P < 0.003) with ADMA, without changes in arginase protein levels. In addition, ADMA treatment resulted in an approximately 30% greater number of viable cells after 48 h than in control bPAEC. These results demonstrate that ADMA is neither a substrate nor an inhibitor of arginase activity and that in bPAEC ADMA inhibits NO production and enhances urea production, leading to more viable cells. These results may have pathophysiological implications in disorders associated with higher ADMA levels, such as pulmonary hypertension.

  6. Physical activity and sedentary behaviour: applying lessons to chronic obstructive pulmonary disease.

    PubMed

    Hill, K; Gardiner, P A; Cavalheri, V; Jenkins, S C; Healy, G N

    2015-05-01

    In health and disease, the benefits of regular participation in moderate to vigorous intensity physical activity are well documented. However, individuals with chronic conditions, such as those with chronic obstructive pulmonary disease (COPD), typically do very little activity at a moderate or vigorous intensity. Much of their day is instead spent in sedentary behaviour, such as sitting or reclining, which requires very little energy expenditure. This high level of time spent in sedentary behaviour can have serious health consequences, including increased risk of diabetes, cardiovascular disease and premature mortality. There is emerging evidence to suggest that participation in light intensity physical activities (e.g. standing or slow walking) may have benefits for cardio-metabolic health. Given the low aerobic capacity of individuals with moderate to severe COPD, increasing light intensity activity (through reducing sedentary time) may be a feasible additional strategy to improve health in this population, alongside traditional recommendations to increase the time spent in moderate to vigorous intensity physical activity. This review provides an overview of physical activity and sedentary behaviour, with a particular emphasis on these behaviours for people with COPD. It provides suggestions for the measurement of these behaviours within the clinical setting, as well as for interventions that may be effective at increasing physical activity and reducing sedentary behaviour in this population.

  7. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla

    2016-01-01

    Objectives Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits. Conclusions Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment. PMID:26981575

  8. Hemoglobin induced cell trauma indirectly influences endothelial TLR9 activity resulting in pulmonary vascular smooth muscle cell activation

    PubMed Central

    Loomis, Zoe; Eigenberger, Paul; Redinius, Katherine; Lisk, Christina; Karoor, Vijaya; Nozik-Grayck, Eva; Ferguson, Scott K.; Hassell, Kathryn; Nuss, Rachelle; Stenmark, Kurt; Buehler, Paul; Irwin, David C.

    2017-01-01

    It is now well established that both inherited and acquired forms of hemolytic disease can promote pulmonary vascular disease consequent of free hemoglobin (Hb) induced NO scavenging, elevations in reactive oxygen species and lipid peroxidation. It has recently been reported that oxidative stress can activate NFkB through a toll-like receptor 9 (TLR9) mediated pathway; further, TLR9 can be activated by either nuclear or mitochondrial DNA liberated by stress induced cellular trauma. We hypothesis that Hb induced lipid peroxidation and subsequent endothelial cell trauma is linked to TLR9 activation, resulting in IL-6 mediated pulmonary smooth muscle cell proliferation. We examined the effects of Hb on rat pulmonary artery endothelial and smooth muscle cells (rPAEC and rPASMC, respectively), and then utilized TLR9 and IL6 inhibitors, as well as the Hb and heme binding proteins (haptoglobin (Hp) and hemopexin (Hpx), respectively) to further elucidate the aforementioned mediators. Further, we explored the effects of Hb in vivo utilizing endothelial cell (EC) specific myeloid differentiation primary response gene-88 (MyD88) and TLR9 null mice. Our data show that oxidized Hb induces lipid peroxidation, cellular toxicity (5.5 ± 1.7 fold; p≤0.04), increased TLR9 activation (60%; p = 0.01), and up regulated IL6 expression (1.75±0.3 fold; p = 0.04) in rPAEC. Rat PASMC exhibited a more proliferative state (13 ± 1%; p = 0.01) when co-cultured with Hb activated rPAEC. These effects were attenuated with the sequestration of Hb or heme by Hp and Hpx as well as with TLR9 an IL-6 inhibition. Moreover, in both EC-MyD88 and TLR9 null mice Hb-infusion resulted in less lung IL-6 expression compared to WT cohorts. These results demonstrate that Hb-induced lipid peroxidation can initiate a modest TLR9 mediated inflammatory response, subsequently generating an activated SMC phenotype. PMID:28152051

  9. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury.

    PubMed

    Hu, Yue; Lou, Jian; Mao, Yuan-Yuan; Lai, Tian-Wen; Liu, Li-Yao; Zhu, Chen; Zhang, Chao; Liu, Juan; Li, Yu-Yan; Zhang, Fan; Li, Wen; Ying, Song-Min; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-12-01

    MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.

  10. Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis.

    PubMed

    Prata, Luana O; Rodrigues, Carolina R; Martins, Jéssica M; Vasconcelos, Paula C; Oliveira, Fabrício Marcus S; Ferreira, Anderson J; Rodrigues-Machado, Maria da Glória; Caliari, Marcelo V

    2017-01-01

    The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM-EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori's trichrome, immunohistochemistry of collagen type I, TGF-β1, beta-prolyl-4-hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-β1 and beta-prolyl-4-hydroxylase and an increase of metalloproteinase -1, -2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis.

  11. Natural killer activity in Fischer-344 rat lungs as a method to assess pulmonary immunocompetence: Immunosuppression by phosgene inhalation

    SciTech Connect

    Burleson, G.R.; Keyes, L.L.

    1989-01-01

    Phosgene is a hazardous air toxic and a potential occupational health hazard. Studies were initiated to determine whether exposure to phosgene resulted in local pulmonary or systemic immune dysfunction. The effect of phosgene on lung natural killer (NK) activity was quantified at different times after exposure. Acute phosgene exposure resulted in a suppressed pulmonary NK activity on days 1, 2, and 4 after exposure; however, normal levels of biological activity were observed 7 days after exposure. The suppressed NK activity was not restored after removal of adherent cells. Pulmonary immunotoxicity was also observed after exposure at 0.5 ppm, while no adverse effects were observed at 0.1 ppm phosgene. Systemic immunotoxic effects were observed for NK activity in the spleen, but not in the peripheral blood. The report is the first of a systemic immunotoxic effect after exposure to phosgene. It is thus important in pulmonary immunotoxicology to evaluate systemic immune functions, since secondary effects -- distant to the original interaction -- may occur with potential serious consequences.

  12. Pulmonary embolus

    MedlinePlus

    ... clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... Main symptoms of a pulmonary embolism include chest pain that may be any of the following: Under the breastbone or on one side Sharp or stabbing ...

  13. Luminescent properties of rare earth fully activated apatites, LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb): site selective crystal field effect.

    PubMed

    Kim, Donghyeon; Park, Doyoung; Oh, Namgyeong; Kim, Jaegyeom; Jeong, Euh Duck; Kim, Seung-Joo; Kim, Sungyun; Park, Jung-Chul

    2015-02-16

    Novel LiCe9(SiO4)6O2 and LiTb9(SiO4)6O2 compounds have been successfully synthesized, and the site selectivity and occupancy of activator ions have been estimated including LiEu9(SiO4)6O2 compound. The rare earth (RE) fully occupied compounds, as well as the RE partially occupied congeners are required for the assessment of site selectivity of RE (activator) ions in apatite-type compounds. The splitting energies of the 6H and 4F Wycoff positions of LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb) compounds are calculated based on crystal field theory: ΔECe(6H) = 3849.3 cm(-1), ΔECe(4F) = 4228.1 cm(-1), ΔEEu(6H) = 3870.0 cm(-1), ΔEEu(4F) = 4092.8 cm(-1), ΔETb(6H) = 3637.6 cm(-1), ΔETb(4F) = 4396.1 cm(-1), indicating that the splitting energy for the 4F site is larger than that for the 6H site in all compounds; thus the absorption energy is higher for the 6H site. In apatite-type LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb) compounds, the Ce(3+) ions predominantly occupy the 4F site associated with the absorption band around 300 nm at lower Ce(3+) concentration, and then enter the 6H site associated the absorption band around 245 nm. For the Eu(3+)-doped compounds, the 4F site and 6H site are mixed within the charge transfer band (CTB) between 220 and 350 nm. Eu(3+) ions initially preferentially occupy the 6H site (around 290 nm) at lower Eu(3+) concentration and subsequently enter the 4F site (around 320 nm) with increasing Eu(3+) concentration. For the Tb(3+)-doped compounds, the absorption due to the two different sites is mixed within f-d absorption band between 200 and 300 nm. At lower Tb(3+) concentration, the Tb(3+) ions enter favorably 6H site around 240 nm and then enter 4F site around 270 nm. These compounds may provide a platform for modeling a new phosphor and application in the solid-state lighting field.

  14. Enhanced pulmonary and active skeletal muscle gas exchange during intense exercise after sprint training in men.

    PubMed Central

    McKenna, M J; Heigenhauser, G J; McKelvie, R S; Obminski, G; MacDougall, J D; Jones, N L

    1997-01-01

    1. This study investigated the effects of 7 weeks of sprint training on gas exchange across the lungs and active skeletal muscle during and following maximal cycling exercise in eight healthy males. 2. Pulmonary oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured before and after training during incremental exercise (n = 8) and during and in recovery from a maximal 30 s sprint exercise bout by breath-by-breath analysis (n = 6). To determine gas exchange by the exercising leg muscles, brachial arterial and femoral venous blood O2 and CO2 contents and lactate concentration were measured at rest, during the final 10 s of exercise and during 10 min of recovery. 3. Training increased (P < 0.05) the maximal incremental exercise values of ventilation (VE, by 15.7 +/- 7.1%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 15.0 +/- 4.2%). Sprint exercise peak power (3.9 +/- 1.0% increase) and cumulative 30 s work (11.7 +/- 2.8% increase) were increased and fatigue index was reduced (by -9.2 +/- 1.5%) after training (P < 0.05). The highest VE, VCO2 and VO2 values attained during sprint exercise were not significantly changed after training, but a significant (P < 0.05) training effect indicated increased VE (by 19.2 +/- 7.9%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 12.7 +/- 6.5%), primarily reflecting elevated post-exercise values after training. 4. Arterial O2 and CO2 contents were lower after training, by respective mean differences of 3.4 and 21.9 ml l-1 (P < 0.05), whereas the arteriovenous O2 and CO2 content differences and the respiratory exchange ratio across the leg were unchanged by training. 5. Arterial whole blood lactate concentration and the net lactate release by exercising muscle were unchanged by training. 6. The greater peak pulmonary VO2 and VCO2 with sprint exercise, the increased maximal incremental values, unchanged arterial blood lactate concentration and greater sprint performance all point strongly towards enhanced gas exchange across the lungs and in

  15. Enhanced pulmonary and active skeletal muscle gas exchange during intense exercise after sprint training in men.

    PubMed

    McKenna, M J; Heigenhauser, G J; McKelvie, R S; Obminski, G; MacDougall, J D; Jones, N L

    1997-06-15

    1. This study investigated the effects of 7 weeks of sprint training on gas exchange across the lungs and active skeletal muscle during and following maximal cycling exercise in eight healthy males. 2. Pulmonary oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured before and after training during incremental exercise (n = 8) and during and in recovery from a maximal 30 s sprint exercise bout by breath-by-breath analysis (n = 6). To determine gas exchange by the exercising leg muscles, brachial arterial and femoral venous blood O2 and CO2 contents and lactate concentration were measured at rest, during the final 10 s of exercise and during 10 min of recovery. 3. Training increased (P < 0.05) the maximal incremental exercise values of ventilation (VE, by 15.7 +/- 7.1%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 15.0 +/- 4.2%). Sprint exercise peak power (3.9 +/- 1.0% increase) and cumulative 30 s work (11.7 +/- 2.8% increase) were increased and fatigue index was reduced (by -9.2 +/- 1.5%) after training (P < 0.05). The highest VE, VCO2 and VO2 values attained during sprint exercise were not significantly changed after training, but a significant (P < 0.05) training effect indicated increased VE (by 19.2 +/- 7.9%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 12.7 +/- 6.5%), primarily reflecting elevated post-exercise values after training. 4. Arterial O2 and CO2 contents were lower after training, by respective mean differences of 3.4 and 21.9 ml l-1 (P < 0.05), whereas the arteriovenous O2 and CO2 content differences and the respiratory exchange ratio across the leg were unchanged by training. 5. Arterial whole blood lactate concentration and the net lactate release by exercising muscle were unchanged by training. 6. The greater peak pulmonary VO2 and VCO2 with sprint exercise, the increased maximal incremental values, unchanged arterial blood lactate concentration and greater sprint performance all point strongly towards enhanced gas exchange across the lungs and in

  16. The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome

    PubMed Central

    Spiropoulou, Christina F; Srikiatkhachorn, Anon

    2013-01-01

    The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity. PMID:23841977

  17. Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

    PubMed

    Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

    2014-11-01

    Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients.

  18. The critical roles of platelet activation and reduced NO bioavailability in fatal pulmonary arterial hypertension in a murine hemolysis model

    PubMed Central

    Hu, Weiguo; Jin, Richard; Zhang, Jinyan; You, Tao; Peng, Zhihai; Ge, Xiaowen; Bronson, Roderick T.; Halperin, Jose A.; Loscalzo, Joseph

    2010-01-01

    Pulmonary arterial hypertension (PAH) is suspected to be a strong mortality determinant of hemolytic disorders. However, direct contribution of acute intravascular hemolysis to fatal PAH has not been investigated. The roles of nitric oxide (NO) insufficiency and platelet activation in hemolysis-associated fatal PAH have been suspected but not been experimentally studied. We recently generated a unique intravascular hemolysis mouse model in which the membrane toxin, intermedilysin (ILY), exclusively lyses the erythrocytes of transgenically expressing human CD59 mice (ThCD59RBC), thereby inducing ILY-dose–dependent massive hemolysis. Using this murine hemolysis model, we found that the acute increase in pulmonary arterial pressure leading to right ventricle failure caused sudden death. Reduced NO bioavailability and massive platelet activation/aggregation leading to the formation of massive thrombosis specifically in the pulmonary microvasculature played the critical roles in pathogenesis of acute hemolysis-associated fatal PAH. Therapeutic interventions enhancing NO bioactivity or inhibiting platelet activation prevented sudden death or prolonged survival time via the suppression of the acute increase in pulmonary arterial pressure and improvement of right ventricle function. These findings further highlight the importance of the inhibition of platelet activation and the enhancement of NO bioavailability for the treatment and prevention of hemolysis-associated (fatal) PAH. PMID:20511540

  19. In vitro angiogenic activity of Aloe vera gel on calf pulmonary artery endothelial (CPAE) cells.

    PubMed

    Lee, M J; Lee, O H; Yoon, S H; Lee, S K; Chung, M H; Park, Y I; Sung, C K; Choi, J S; Kim, K W

    1998-06-01

    Angiogenic activity of Aloe vera gel was investigated by in vitro assay. We obtained the most active fraction from dichloromethane extract of Aloe vera gel by partitioning between hexane and 90% aqueous methanol. The most active fraction (F3) increased the proliferation of calf pulmonary artery endothelial (CPAE) cells. In addition, F3 fraction induced CPAE cells to invade type 1 collagen gel and form capillary-like tube through in vitro angiogenesis assay, and increased the invasion of CPAE cells into matrigel through in vitro invasion assay. Furthermore, the effect on the mRNA expression of proteolytic enzymes which are key participants in the regulation of extracellular matrix degradation was investigated by northern blot analysis. F3 fraction enhanced mRNA expression of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase-2 (MMP-2), and membrane-type MMP (MT-MMP) in CPAE cells whereas the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA was not changed.

  20. New drugs and regimens for treatment of TB

    PubMed Central

    Leibert, Eric; Rom, William N

    2013-01-01

    Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms. PMID:20586565

  1. [Pulmonary alveolar microlithiasis. Study of pulmonary circulation].

    PubMed

    Orea Tejeda, A; Atencio, C; Sandoval, J; Lupi Herrera, E

    1982-01-01

    Pulmonary alveolar microlithiasis is a rare disease of unknown etiology which consists of alveolar deposit of calcium microspheres. We report the procedures for the diagnosis of this disease, as well as the hemodynamic features of the pulmonary circulation. Pulmonary arterial hypertension (PAH), and cor pulmonale were documented. The active and passive factors involved in PAH are analyzed. We conclude that alveolar hypoxia and estructural vascular changes play a major role in the genesis of PAH.

  2. [Tuberculosis annual report 2009 --series 10. Treatment outcome and TB deaths].

    PubMed

    2012-05-01

    Evaluation of the treatment outcome by the cohort analysis method is an important part of tuberculosis (TB) control. In the Japanese TB surveillance system, the treatment outcome is automatically classified by computer according to a pre-set algorithm, so the treatment outcome is evaluated very rigidly. In the case of new sputum smear positive pulmonary TB cases (n = 8,999) newly notified in 2008, the patients' treatment outcomes based on the annual report 2009 database were as follows: "success," which combined "cured" and "completed," was 47.7%, "died" was 19.1%, "failed" was 1.1%, "defaulted" was 3.8%, "transferred out" was 2.8%, "on treatment after 12 months" was 11.8% and "not evaluated" was 13.6%. In addition to evaluation of the treatment outcome by the cohort method, the proportion of deaths was observed among all forms of TB patients (n = 24,571) who were newly registered in 2008. In total, 17.3% of all forms of TB cases died within one year after the beginning of treatment. The proportion corresponding to this was 23.7% for new sputum smear positive pulmonary TB and 23.5% for re-treatment sputum smear positive pulmonary TB. Among the new sputum smear positive pulmonary TB patients (n = 2,136) who died within one year after the beginning of treatment, 37.0% of them died within one month after the beginning of treatment, 51.6% died within two months and 61.9% died within three months.

  3. 18F-flouro-2-deoxyglucose positron emission tomography/computed tomography imaging of solitary prostatic and pulmonary tuberculosis mimicking metastatic prostate cancer.

    PubMed

    Kadihasanoglu, Mustafa; Yildiz, Tekin; Atahan, Safak; Ausmus, Andrew; Atahan, Ozcan

    2015-01-01

    Genitourinary tuberculosis (TB) is a common type of extrathoracic TB and can be found in isolation or associated with pulmonary TB. It contributes to 10-14% of extrapulmonary TB. Prostate TB is rare and usually found incidentally following transurethral resection of the prostate for treatment of benign prostatic obstruction as an isolated lesion in immunocompetant patient. The authors report a case of prostatic and pulmonary TB in animmunocompetant patient investigating for the positive positron emission tomography in lung and prostate. To our knowledge, this is the first case reported in the literature presenting with simultaneous hypermetabolic lesions in the prostate and lung.

  4. Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants.

    PubMed

    Liu, Xueting; Chen, Caixia; He, Wenni; Huang, Pei; Liu, Miaomiao; Wang, Qian; Guo, Hui; Bolla, Krishna; Lu, Yan; Song, Fuhang; Dai, Huanqin; Liu, Mei; Zhang, Lixin

    2012-10-01

    Multidrug-resistant tuberculosis (MDR-TB) and TB-HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40 years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.

  5. Are We Doing Enough to Stem the Tide of Acquired MDR-TB in Countries with High TB Burden? Results of a Mixed Method Study in Chongqing, China

    PubMed Central

    Li, Ying; Ehiri, John; Oren, Eyal; Hu, Daiyu; Luo, Xingneng; Liu, Ying; Li, Daikun; Wang, Qingya

    2014-01-01

    Multi-drug resistant tuberculosis (MDR-TB) represents a threat to health and development in countries with high TB burden. China’s MDR-TB prevalence rate of 6.8% is the highest in the world. Interventions to remove barriers against effective TB control, and prevention of MDR-TB are urgently needed in the country. This paper reports a cross-sectional questionnaire survey of 513 pulmonary TB (PTB) patients, and qualitative interviews of 10 healthcare workers (HCWs), and 15 PTB patients. The objective was to assess barriers against effective control of PTB and prevention of MDR-TB by elucidating the perspectives of patients and healthcare providers. Results showed that more than half of the patients experienced patient delay of over 12.5 days. A similar proportion also experienced detection delay of over 30 days, and delay in initiating treatment of over 31 days. Consulting a non-TB health facility ≥3 times before seeking care at TB dispensary was a risk factor for both detection delay [AOR (95% CI): 1.89(1.07, 3.34) and delay in initiating treatment[AOR (95% CI): 1.88 (1.06, 3.36). Results revealed poor implementation of Directly Observed Therapy (DOT), whereby treatment of 34.3% patients was never monitored by HCWs. Only 31.8% patients had ever accessed TB health education before their TB diagnosis. Qualitative data consistently disclosed long patient delay, and indicated that patient’s poor TB knowledge and socioeconomic barriers were primary reasons for patient delay. Seeking care and being treated at a non-TB hospital was an important reason for detection delay. Patient’s long work hours and low income increased risk for treatment non-adherence. Evidence-based measures to improve TB health seeking behavior, reduce patient and detection delays, improve the quality of DOT, address financial and system barriers, and increase access to TB health promotion are urgently needed to address the burgeoning prevalence of MDR-TB in China. PMID:24505476

  6. Are we doing enough to stem the tide of acquired MDR-TB in countries with high TB burden? Results of a mixed method study in Chongqing, China.

    PubMed

    Li, Ying; Ehiri, John; Oren, Eyal; Hu, Daiyu; Luo, Xingneng; Liu, Ying; Li, Daikun; Wang, Qingya

    2014-01-01

    Multi-drug resistant tuberculosis (MDR-TB) represents a threat to health and development in countries with high TB burden. China's MDR-TB prevalence rate of 6.8% is the highest in the world. Interventions to remove barriers against effective TB control, and prevention of MDR-TB are urgently needed in the country. This paper reports a cross-sectional questionnaire survey of 513 pulmonary TB (PTB) patients, and qualitative interviews of 10 healthcare workers (HCWs), and 15 PTB patients. The objective was to assess barriers against effective control of PTB and prevention of MDR-TB by elucidating the perspectives of patients and healthcare providers. Results showed that more than half of the patients experienced patient delay of over 12.5 days. A similar proportion also experienced detection delay of over 30 days, and delay in initiating treatment of over 31 days. Consulting a non-TB health facility ≥3 times before seeking care at TB dispensary was a risk factor for both detection delay [AOR (95% CI): 1.89(1.07, 3.34) and delay in initiating treatment[AOR (95% CI): 1.88 (1.06, 3.36). Results revealed poor implementation of Directly Observed Therapy (DOT), whereby treatment of 34.3% patients was never monitored by HCWs. Only 31.8% patients had ever accessed TB health education before their TB diagnosis. Qualitative data consistently disclosed long patient delay, and indicated that patient's poor TB knowledge and socioeconomic barriers were primary reasons for patient delay. Seeking care and being treated at a non-TB hospital was an important reason for detection delay. Patient's long work hours and low income increased risk for treatment non-adherence. Evidence-based measures to improve TB health seeking behavior, reduce patient and detection delays, improve the quality of DOT, address financial and system barriers, and increase access to TB health promotion are urgently needed to address the burgeoning prevalence of MDR-TB in China.

  7. Hyperosmolarity attenuates TNFα–mediated pro-inflammatory activation of human pulmonary microvascular endothelial cells

    PubMed Central

    Banerjee, Anirban; Moore, Ernest E.; McLaughlin, Nathan J.; Lee, Luis; Jones, Wilbert L.; Johnson, Jeffrey L.; Nydam, Trevor L.; Silliman, Christopher C.

    2013-01-01

    Firm neutrophil (PMN)-endothelial (EC) adhesion is crucial to the PMN-mediated hyperinflammation observed in acute lung injury. Hypertonic saline (HTS) used for resuscitation of hemorrhagic shock has been associated with a decreased incidence of PMN-mediated lung injury/acute respiratory distress syndrome. We hypothesize that physiologically accessible hypertonic incubation (170mM vs. 140mM, osmolarity ranging from 360-300 mOsm/L) inhibits pro-inflammatory activation of human pulmonary microvascular endothelial cells (HMVECs). Pro-inflammatory activation of HMVECs was investigated in response to TNFα including IL-8 release, ICAM-1 surface expression, PMN adhesion, and signaling mechanisms under both isotonic (control) and hypertonic conditions. Hyperosmolarity alone had no effect on either basal IL-8 release or ICAM-1 surface expression, but did lead to concentration-dependent decreases in TNFα–induced IL-8 release, ICAM-1 surface expression, and PMN:HMVEC adhesion. Conversely, HTS activated p38 mitogen-activated protein kinase (MAPK) and enhanced TNFα activation of p38 MAPK. Despite this basal activation, hyperosmolar incubation attenuated TNFα stimulated IL-8 release and ICAM-1 surface expression and subsequent PMN adherence, while p38 MAPK inhibition did not further influence the effects of hyperosmolar conditions on ICAM-1 surface expression. In addition, TNFα induced NF-kB DNA binding, but HTS conditions attenuated this by 31% (p<0.01). In conclusion, HTS reduces PMN:HMVEC adhesion as well as TNFα-induced pro-inflammatory activation of primary HMVECs via attenuation of NF-kB signaling. PMID:23364439

  8. Patient's Perception of Symptoms Related to Morning Activity in Chronic Obstructive Pulmonary Disease: The SYMBOL Study

    PubMed Central

    Kim, Yeon Jae; Lee, Byung Ki; Jung, Chi Young; Jeon, Young June; Hyun, Dae Sung; Kim, Kyung Chan; Yu, Sung Ken; Choi, Hye Sook; Shin, Won Hyuk

    2012-01-01

    Background/Aims Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning. The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation. Methods Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study. A clinical symptom questionnaire was completed by patients at baseline. In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment. Results The most frequently reported COPD symptom was breathlessness (90.8%). Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms. The most frequently reported morning activity was getting out of bed (82.9%). The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms. There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment. Conclusions Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities. These patients also have more prevalent and severe COPD symptoms. The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD. PMID:23269884

  9. Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes.

    PubMed

    Okamoto, Yosuke; Kawamura, Koichi; Nakamura, Yuta; Ono, Kyoichi

    2014-01-01

    Pulmonary veins (PVs) are believed to be a crucial origin of atrial fibrillation. We recently reported that rat PV cardiomyocytes exhibit arrhythmogenic automaticity in response to norepinephrine. Herein, we further characterized the electrophysiological properties underlying the potential arrhythmogenicity of PV cardiomyocytes. Patch clamping studies revealed a time dependent hyperpolarization-activated inward current in rat PV cardiomyocytes, but not in left atrial (LA) myocytes. The current was Cs(+) resistant, and was not affected by removal of external Na(+) or K(+). The current was inhibited with Cd(2+), and the reversal potential was sensitive to changes in [Cl(-)] on either side of the membrane in a manner consistent with a Cl(-) selective channel. Cl(-) channel blockers attenuated the current, and slowed or completely inhibited the norepinephrine-induced automaticity. The biophysical properties of the hyperpolarization-activated Cl(-) current in rat PVs were different from those of ClC-2 currents previously reported: (i) the voltage-dependent activation of the Cl(-) current in rat PVs was shifted to negative potentials as [Cl(-)]i increased, (ii) the Cl(-) current was enhanced by extracellular acidification, and (iii) extracellular hyper-osmotic stress increased the current, whereas hypo-osmotic cell swelling suppressed the current. qPCR analysis revealed negligible ClC-2 mRNA expression in the rat PV. These findings suggest that rat PV cardiomyocytes possess a peculiar voltage-dependent Cl(-) channel, and that the channel may play a functional role in norepinephrine-induced automaticity.

  10. Interleukin-17 is not required for classical macrophage activation in a pulmonary mouse model of Cryptococcus neoformans infection.

    PubMed

    Hardison, Sarah E; Wozniak, Karen L; Kolls, Jay K; Wormley, Floyd L

    2010-12-01

    Cryptococcus neoformans is an opportunistic fungal pathogen that causes disease in individuals with suppressed cell-mediated immunity. Recent studies in our laboratory have shown that increases in pulmonary Th1-type and interleukin-17A (IL-17A) cytokine production, classical macrophage activation, and sterilizing immunity are elicited in response to infection with a gamma interferon (IFN-γ)-producing C. neoformans strain, H99γ. IL-17A-treated macrophages, compared to IL-4-treated macrophages, have been demonstrated to exhibit increased microbicidal activity in vitro, a characteristic consistent with classical macrophage activation. The purpose of these studies is to determine the role of IL-17A in the induction of classically activated macrophages following infection with C. neoformans. Immunohistochemistry and real-time PCR were used to characterize the macrophage activation phenotype in lung tissues of mice treated with isotype control or anti-IL-17A antibodies and given an experimental pulmonary infection with C. neoformans strain H99γ. The pulmonary fungal burden was resolved, albeit more slowly, in mice depleted of IL-17A compared to the fungal burden in isotype control-treated mice. Nonetheless, no difference in classical macrophage activation was observed in IL-17A-depleted mice. Similarly, classical macrophage activation was evident in mice deficient in IL-17A or the IL-17 receptor A, which mediates IL-17A signaling, following pulmonary infection with wild-type C. neoformans strain H99 or H99γ. These studies suggest that IL-17A may play a role in the early immune response to C. neoformans but is not required for classical macrophage activation in mice experimentally infected with C. neoformans.

  11. Association of platelet activation markers with recurrence of atrial fibrillation after pulmonary vein isolation.

    PubMed

    Pfluecke, Christian; Plichta, Lina; Tarnowski, Daniel; Forkmann, Mathias; Ulbrich, Stefan; Quick, Silvio; Heidrich, Felix M; Wiedemann, Stephan; Christoph, Marian; Poitz, David M; Wunderlich, Carsten; Strasser, Ruth H; Ibrahim, Karim

    2016-10-13

    Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.

  12. Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil

    PubMed Central

    Castro, Simone; Cafezeiro, Aparecida S.; Daltro, Carla; Netto, Eduardo M.; Kornfeld, Hardy; Andrade, Bruno B.

    2016-01-01

    Background Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. Methods Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. Results The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. Conclusions Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted. PMID:27078026

  13. Intention to Quit Smoking and Associated Factors in Smokers Newly Diagnosed with Pulmonary Tuberculosis

    PubMed Central

    Aryanpur, Mahshid; Mortaz, Esmaeil; Hosseini, Mostafa; Jamaati, Hmidreza; Tabarsi, Payam; Soori, Hamid; Heydari, Gholam Reza; Kazempour-Dizaji, Mehdi; Emami, Habib; Mozafarian, Alireza

    2016-01-01

    Background: Several studies have shown that smoking, as a modifiable risk factor, can affect tuberculosis (TB) in different aspects such as enhancing development of TB infection, activation of latent TB and its related mortality. Since willingness to quit smoking is a critical stage, which may lead to quit attempts, being aware of smokers’ intention to quit and the related predictors can provide considerable advantages. Materials and Methods: In this cross-sectional study, subjects were recruited via a multi-stage cluster sampling method. Sampling was performed during 2012–2014 among pulmonary TB (PTB) patients referred to health centers in Tehran implementing the directly observed treatment short course (DOTS) strategy and a TB referral center. Data analysis was conducted using SPSS version 22 and the factors influencing quit intention were assessed using bivariate regression and multiple logistic regression models. Results: In this study 1,127 newly diagnosed PTB patients were studied; from which 284 patients (22%) were current smokers. When diagnosed with TB, 59 (23.8%) smokers quit smoking. Among the remaining 189 (76.2%) patients who continued smoking, 52.4% had intention to quit. In the final multiple logistic regression model, living in urban areas (OR=8.81, P=0.003), having an office job (OR= 7.34, P=0.001), being single (OR=4.89, P=0.016) and a one unit increase in the motivation degree (OR=2.60, P<0.001) were found to increase the intention to quit smoking. Conclusion: The study found that PTB patients who continued smoking had remarkable intention to quit. Thus, it is recommended that smoking cessation interventions should be started at the time of TB diagnosis. Understanding the associated factors can guide the consultants to predict patients’ intention to quit and select the most proper management to facilitate smoking cessation for each patient. PMID:27403174

  14. Activation of AMPK inhibits PDGF-induced pulmonary arterial smooth muscle cells proliferation and its potential mechanisms.

    PubMed

    Song, Yang; Wu, Yuanyuan; Su, Xiaofan; Zhu, Yanting; Liu, Lu; Pan, Yilin; Zhu, Bo; Yang, Lan; Gao, Li; Li, Manxiang

    2016-05-01

    The aims of the present study were to examine signaling mechanisms for PDGF-induced pulmonary arterial smooth muscle cells (PASMC) proliferation and to determine the effect of AMPK activation on PDGF-induced PASMC proliferation and its underlying mechanisms. PDGF activated PI3K/Akt/mTOR signaling pathway, and this in turn up-regulated Skp2 and consequently reduced p27 leading to PASMC proliferation. Prior incubation of PASMC with metformin induced a dramatic AMPK activation and significantly blocked PDGF-induced cell proliferation. PASMC lacking AMPKα2 were resistant to the inhibitory effect of metformin on PDGF-induced cell proliferation. Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction. Our study suggests that the activation of AMPK negatively regulates mTOR activity to suppress PASMC proliferation and therefore has a potential value in the prevention and treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.

  15. Genome-Wide Expression Profiling Identifies Type 1 Interferon Response Pathways in Active Tuberculosis

    PubMed Central

    Ottenhoff, Tom H. M.; Zhang, Mingzi M.; Wong, Hazel E. E.; Sahiratmadja, Edhyana; Khor, Chiea Chuen; Alisjahbana, Bachti; van Crevel, Reinout; Marzuki, Sangkot; Seielstad, Mark; van de Vosse, Esther; Hibberd, Martin L.

    2012-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains the leading cause of mortality from a single infectious agent. Each year around 9 million individuals newly develop active TB disease, and over 2 billion individuals are latently infected with M.tb worldwide, thus being at risk of developing TB reactivation disease later in life. The underlying mechanisms and pathways of protection against TB in humans, as well as the dynamics of the host response to M.tb infection, are incompletely understood. We carried out whole-genome expression profiling on a cohort of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment. We identified molecular signatures involving the upregulation of type-1 interferon (α/β) mediated signaling and chronic inflammation during active TB disease in an Indonesian population, in line with results from two recent studies in ethnically and epidemiologically different populations in Europe and South Africa. Expression profiles were captured in neutrophil-depleted blood samples, indicating a major contribution of lymphocytes and myeloid cells. Expression of type-1 interferon (α/β) genes mediated was also upregulated in the lungs of M.tb infected mice and in infected human macrophages. In patients, the regulated gene expression-signature normalized during treatment, including the type-1 interferon mediated signaling and a concurrent opposite regulation of interferon-gamma. Further analysis revealed IL15RA, UBE2L6 and GBP4 as molecules involved in the type-I interferon response in all three experimental models. Our data is highly suggestive that the innate immune type-I interferon signaling cascade could be used as a quantitative tool for monitoring active TB disease, and provide evidence that components of the patient’s blood gene expression signature bear similarities to the pulmonary and macrophage response to mycobacterial infection

  16. Calcium-activated chloride channels in bovine pulmonary artery endothelial cells.

    PubMed Central

    Nilius, B; Prenen, J; Szücs, G; Wei, L; Tanzi, F; Voets, T; Droogmans, G

    1997-01-01

    1. We characterized Ca(2+)-activated Cl- currents in calf pulmonary artery endothelial (CPAE) cells by using a combined patch clamp and fura-2 microfluorescence technique to simultaneously measure ionic currents and the intracellular Ca2+ concentration, [Ca2+]i. 2. Various procedures that increased [Ca2+]i, such as stimulation with ATP or ionomycin, or loading the cells with Ca2+ via the patch pipette, activated a strongly outwardly rectifying current with a reversal potential close to the Cl- equilibrium potential. Changing the extracellular Cl- concentration shifted this reversal potential as predicted for a Cl- current. Buffering Ca2+ rises with BAPTA prevented ATP from activating the current. 3. Ca(2+)-activated Cl- currents could be distinguished from volume-activated Cl- currents, which were sometimes coactivated in the same cell. The latter showed much less outward rectification, their activation was voltage independent, and they could be inhibited by exposing the cells to hypertonic solutions. 4. The permeability ratio for the Ca(2+)-activated conductance of the anions iodide:chloride: gluconate was 1.71 +/- 0.06:1:0.39 +/- 0.03 (n = 12). 5. This Ca(2+)-activated Cl- current, ICl, Ca, inactivated rapidly at negative potentials and activated slowly at positive potentials. Outward tail currents were slowly decaying, while inward tail currents decayed much faster. 6. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonic-acid (DIDS) and niflumic acid inhibited Icl,Ca in a voltage-dependent manner, i.e. they exerted a more potent block at positive potentials. The block by N-phenylanthracilic acid (NPA), 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and tamoxifen was voltage independent. Niflumic acid and tamoxifen were the most potent blockers. 7. The single-channel conductance was 7.9 +/- 0.7 pS (n = 15) at 300 mM extracellular Cl-. The channel open probability was high at positive potentials, but very small at negative potentials. 8. It is concluded that [Ca2+]i

  17. Physical Activity, Health Status and Risk of Hospitalization in Patients with Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    Benzo, Roberto P.; Chang, Chung-Chou H.; Farrell, Max H.; Kaplan, Robert; Ries, Andrew; Martinez, Fernando J.; Wise, Robert; Make, Barry; Sciurba, Frank

    2010-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a leading cause of death and 70% of the cost of COPD is due to hospitalizations. Self-reported daily physical activity and health status have been reported as predictors of a hospitalization in COPD but are not routinely assessed. Objectives We tested the hypothesis that self-reported daily physical activity and health status assessed by a simple question were predictors of a hospitalization in a well-characterized cohort of patients with severe emphysema. Methods Investigators gathered daily physical activity and health status data assessed by a simple question in 597 patients with severe emphysema and tested the association of those patient-reported outcomes to the occurrence of a hospitalization in the following year. Multiple logistic regression analyses were used to determine predictors of hospitalization during the first 12 months after randomization. Results The two variables tested in the hypothesis were significant predictors of a hospitalization after adjusting for all univariable significant predictors: >2 h of physical activity per week had a protective effect [odds ratio (OR) 0.60; 95% confidence interval (95% CI) 0.41–0.88] and self-reported health status as fair or poor had a deleterious effect (OR 1.57; 95% CI 1.10–2.23). In addition, two other variables became significant in the multivariate model: total lung capacity (every 10% increase) had a protective effect (OR 0.88; 95% CI 0.78–0.99) and self-reported anxiety had a deleterious effect (OR 1.75; 95% CI 1.13–2.70). Conclusion Self-reported daily physical activity and health status are independently associated with COPD hospitalizations. Our findings, assessed by simple questions, suggest the value of patient-reported outcomes in developing risk assessment tools that are easy to use. PMID:20234126

  18. Peroxisome proliferator activated receptor-γ-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension

    PubMed Central

    Tseng, Nancy; Seedorf, Gregory; Roe, Gates; Abman, Steven H.

    2013-01-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) and Rho-kinase (ROCK) regulate smooth muscle cell (SMC) proliferation and contribute to vascular remodeling in adult pulmonary hypertension. Whether these pathways interact to contribute to the development of vascular remodeling in persistent pulmonary hypertension of the newborn (PPHN) remains unknown. We hypothesized that ROCK-PPARγ interactions increase SMC proliferation resulting in vascular remodeling in experimental PPHN. Pulmonary artery SMCs (PASMCs) were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and controls. Cell counts were performed daily for 5 days with or without PPARγ agonists and ROCK inhibition. PPARγ and ROCK protein expression/activity were measured by Western blot in normal and PPHN PASMCs. We assessed PPARγ-ROCK interactions by studying the effect of ROCK activation on PPARγ activity and PPARγ inhibition (siRNA) on ROCK activity and PASMC proliferation. At baseline, PPHN PASMC cell number was increased by 38% above controls on day 5. ROCK protein expression/activity were increased by 25 and 34% and PPARγ protein/activity decreased by 40 and 50% in PPHN PASMC. ROCK inhibition and PPARγ activation restored PPHN PASMC growth to normal values. ROCK inhibition increased PPARγ activity by 50% in PPHN PASMC, restoring PPARγ activity to normal. In normal PASMCs, ROCK activation decreased PPARγ activity and PPARγ inhibition increased ROCK activity and cell proliferation, resulting in a PPHN hyperproliferative PASMC phenotype. PPARγ-ROCK interactions regulate SMC proliferation and contribute to increased PPHN PASMC proliferation and vascular remodeling in PPHN. Restoring normal PPARγ-ROCK signaling may prevent vascular remodeling and improve outcomes in PPHN. PMID:24375792

  19. Luminescent properties of Tb-activated rare-earth oxyapatite silicate MLn4Si3O13 (M = Ca, Sr, Ln = La, Gd)

    NASA Astrophysics Data System (ADS)

    Yamane, A.; Kunimoto, T.; Ohmi, K.; Honma, T.; Kobayashi, H.

    2006-09-01

    Rare-earth oxyapatites MLn4Si3O13 (M = Ca, Sr, Ba Ln = La, Gd) have been proposed as a new plasma display panel (PDP) host material to overcome the problems of Zn2SiO4:Mn commercial green phosphor, such as luminance degradation and poor surface charge. Tb-doped MLn4Si3O13 phosphor powders show a green luminescence with the CIE color coordinate (x, y) = (0.337, 0.562). The PL excitation band lies continuously in the wavelength region from 130 to 260 nm. The photoluminescence (PL) peak intensity of SrGd4Si3O13:Tb is comparable with that of Zn2SiO4:Mn. The phosphor is a candidate for a green PDP phosphor for Xe2 excitation.

  20. Active case finding strategy for chronic obstructive pulmonary disease with handheld spirometry.

    PubMed

    Kim, Joo Kyung; Lee, Chang Min; Park, Ji Young; Kim, Joo Hee; Park, Sung-Hoon; Jang, Seung Hun; Jung, Ki-Suck; Yoo, Kwang Ha; Park, Yong Bum; Rhee, Chin Kook; Kim, Deog Kyeom; Hwang, Yong Il

    2016-12-01

    The early detection and diagnosis of chronic obstructive pulmonary disease (COPD) is critical to providing appropriate and timely treatment. We explored a new active case-finding strategy for COPD using handheld spirometry.We recruited subjects over 40 years of age with a smoking history of more than 10 pack-years who visited a primary clinic complaining of respiratory symptoms. A total of 190 of subjects were enrolled. Medical information was obtained from historical records and physical examination by general practitioners. All subjects had their pulmonary function evaluated using handheld spirometry with a COPD-6 device. Because forced expiratory volume in 6 seconds (FEV6) has been suggested as an alternative to FVC, we measured forced expiratory volume in 1 second (FEV1)/FEV6 for diagnosis of airflow limitation. All subjects were then referred to tertiary referral hospitals to complete a "Could it be COPD?" questionnaire, handheld spiromtery, and conventional spirometry. The results of each instrument were compared to evaluate the efficacy of both handheld spirometry and the questionnaire.COPD was newly diagnosed in 45 (23.7%) patients. According to our receiver-operating characteristic (ROC) curve analysis, sensitivity and specificity were maximal when the FEV1/FEV6 ratio was less than 77%. The area under the ROC curve was 0.759. The sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 77.1%, 50%, and 90%, respectively. The area under the ROC curve of respiratory symptoms listed on the questionnaire ranged from 0.5 to 0.65, which indicates that there is almost no difference compared with the results of handheld spirometry.The present study demonstrated the efficacy of handheld spirometry as an active case-finding tool for COPD in a primary clinical setting. This study suggested that physicians should recommend handheld spirometry for people over the age of 40, who have a smoking history of more than 10 pack

  1. Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

    PubMed Central

    Norel, Xavier; Walch, Laurence; Gascard, Jean-Pierre; Montpreville, Vincent de; Brink, Charles

    2004-01-01

    In human pulmonary vascular preparations, precontracted arteries were more sensitive to the relaxant effect of acetylcholine (ACh) than veins (pD2 values: 7.25±0.08 (n=23) and 5.92±0.09 (n=25), respectively). Therefore, the role of prostacyclin (PGI2) was explored to examine whether this mediator may be responsible for the difference in relaxation. In the presence of the cyclooxygenase (COX) inhibitor, indomethacin (INDO), the ACh relaxations were reduced in arteries but not in veins. On the contrary, an inhibitor (L-NOARG) of the nitric oxide synthase blocked preferentially the relaxation in veins. A greater release of 6-keto-PGF1α, the stable metabolite of PGI2, was observed in arterial preparations than in venous preparations when stimulated with either ACh or arachidonic acid (AA). Exogenous PGI2 produced a reduced relaxant effect in the precontracted vein when compared with the artery. In the presence of the EP1-receptor antagonist AH6809, the PGI2 relaxation of veins was similar to arteries. In veins, AA (0.1 mM) produced a biphasic response, namely, a contraction peak (0.4–0.5 g) followed by a relaxation. These contractions in venous preparations were abolished either in the absence of endothelium or in the presence of INDO or an EP1-receptor antagonist (AH6809, SC19220). In the arterial preparations AA induced only relaxations. In both vascular preparations, COX-1 but not the COX-2 protein was detected in microsomal preparations derived from homogenized tissues or freshly isolated endothelial cells. The differential vasorelaxations induced by ACh may be explained, in part, by a more pronounced production and release of PGI2 in human pulmonary arteries than in the veins. In addition, while PGI2 induced relaxation by activation of IP-receptors in both types of vessels, a PGI2 constrictor effect was responsible for masking the relaxation in the veins by activation of the EP1-receptor. PMID:15172959

  2. Active case finding strategy for chronic obstructive pulmonary disease with handheld spirometry

    PubMed Central

    Kim, Joo Kyung; Lee, Chang Min; Park, Ji Young; Kim, Joo Hee; Park, Sung-hoon; Jang, Seung Hun; Jung, Ki-Suck; Yoo, Kwang Ha; Park, Yong Bum; Rhee, Chin Kook; Kim, Deog Kyeom; Hwang, Yong Il

    2016-01-01

    Abstract The early detection and diagnosis of chronic obstructive pulmonary disease (COPD) is critical to providing appropriate and timely treatment. We explored a new active case-finding strategy for COPD using handheld spirometry. We recruited subjects over 40 years of age with a smoking history of more than 10 pack-years who visited a primary clinic complaining of respiratory symptoms. A total of 190 of subjects were enrolled. Medical information was obtained from historical records and physical examination by general practitioners. All subjects had their pulmonary function evaluated using handheld spirometry with a COPD-6 device. Because forced expiratory volume in 6 seconds (FEV6) has been suggested as an alternative to FVC, we measured forced expiratory volume in 1 second (FEV1)/FEV6 for diagnosis of airflow limitation. All subjects were then referred to tertiary referral hospitals to complete a “Could it be COPD?” questionnaire, handheld spiromtery, and conventional spirometry. The results of each instrument were compared to evaluate the efficacy of both handheld spirometry and the questionnaire. COPD was newly diagnosed in 45 (23.7%) patients. According to our receiver-operating characteristic (ROC) curve analysis, sensitivity and specificity were maximal when the FEV1/FEV6 ratio was less than 77%. The area under the ROC curve was 0.759. The sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 77.1%, 50%, and 90%, respectively. The area under the ROC curve of respiratory symptoms listed on the questionnaire ranged from 0.5 to 0.65, which indicates that there is almost no difference compared with the results of handheld spirometry. The present study demonstrated the efficacy of handheld spirometry as an active case-finding tool for COPD in a primary clinical setting. This study suggested that physicians should recommend handheld spirometry for people over the age of 40, who have a smoking history of more than

  3. UV-VUV-excited photoluminescence of RE-activated CaLaP{sub 3}O{sub 10} (RE=Eu,Tb)

    SciTech Connect

    Wu Chunfang; Wang Yuhua . E-mail: wyh@lzu.edu.cn; Liu Wenjing

    2006-12-15

    Monazite-type polyphosphate CaLaP{sub 3}O{sub 10} was synthesized by solid-state reaction at 1000 deg. C and their photoluminescence of Eu{sup 3+} and Tb{sup 3+} in CaLaP{sub 3}O{sub 10} under ultraviolet (UV) and vacuum-ultraviolet (VUV) excitation were evaluated for the first time. The emission spectra of CaLaP{sub 3}O{sub 10}:Eu{sup 3+}showed that Eu{sup 3+} are in a site with inversion symmetry because the magnetic dipole transition {sup 5} D {sub 0}-{sup 7} F {sub 1} was the strongest both upon 254 and 147 nm excitation. Monitored at 621 nm the excitation spectra consisted of host absorption bands, charge transfer band of Eu-O and the intraconfiguration 4f {sup 6} transition of Eu{sup 3+}. Green phosphor CaLaP{sub 3}O{sub 10}:Tb{sup 3+}exhibited better color purity when excited by 147 nm than that excited by 254 nm. With monitored at 542 nm the host absorption bands of CaLaP{sub 3}O{sub 10}:Tb{sup 3+} were also observed. Besides the host absorption bands there were strong f-d and weak f-f transitions of Tb{sup 3+}. - Graphical abstract: Excitation spectra of CaLa{sub 0.85}P{sub 3}O{sub 10}:0.15Eu{sup 3+} ({lambda} {sub em}=620 nm)

  4. Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity.

    PubMed

    Gilio, Joyce M; Marcondes, Marcelo F; Ferrari, Débora; Juliano, Maria A; Juliano, Luiz; Oliveira, Vitor; Machado, Maurício F M

    2017-04-01

    Metacaspases are members of the cysteine peptidase family and may be implicated in programmed cell death in plants and lower eukaryotes. These proteases exhibit calcium-dependent activity and specificity for arginine residues at P1. In contrast to caspases, they do not require processing or dimerization for activity. Indeed, unprocessed metacaspase-2 of Trypanosoma brucei (TbMCA2) is active; however, it has been shown that cleavages at Lys(55) and Lys(268) increase TbMCA2 hydrolytic activity on synthetic substrates. The processed TbMCA2 comprises 3 polypeptide chains that remain attached by non-covalent bonds. Replacement of Lys(55) and Lys(268) with Gly via site-directed mutagenesis results in non-processed but enzymatically active mutant, TbMCA2 K55/268G. To investigate the importance of this processing for the activity and specificity of TbMCA2, we performed activity assays comparing the non-processed mutant (TbMCA2 K55/268G) with the processed TbMCA2 form. Significant differences between TbMCA2 WT (processed form) and TbMCA2 K55/268G (non-processed form) were observed. Specifically, we verified that although non-processed TbMCA2 is active when assayed with small synthetic substrates, the TbMCA2 form does not exhibit hydrolytic activity on large substrates such as azocasein, while processed TbMCA2 is able to readily digest this protein. Such differences can be relevant for understanding the physiological regulation and function of TbMCA2.

  5. Balance recovery is compromised and trunk muscle activity is increased in chronic obstructive pulmonary disease.

    PubMed

    Smith, Michelle D; Chang, Angela T; Hodges, Paul W

    2016-01-01

    Increased respiration in chronic obstructive pulmonary disease (COPD) requires greater abdominal muscle activation, which may impact on contribution of the trunk to postural control. This study aimed to determine whether recovery of balance from postural perturbations and trunk muscle activity differs in people with and without COPD before and/or after exercise. Electromyography (EMG) of the obliquus internus (OI) and externus (OE) abdominis, rectus abdominis (RA), erector spinae (ES) and deltoid muscles was recorded with surface electrodes during rapid shoulder flexion and extension. Time taken to regain baseline centre of pressure velocity (vCOP) and the number of postural adjustments following arm movement was calculated from force plate data. Time to recover balance in the direction of postural disturbance (anteroposterior vCOP) was longer in COPD, particularly more severe COPD, than controls. Mediolateral vCOP (perpendicular to the perturbation) and the number of postural adjustments did not differ between groups, but people with more severe COPD were less successful at returning their mediolateral vCOP to baseline. Abdominal muscle EMG was similar between groups, but controls had greater ES EMG during arm movements. Individuals with more severe COPD had greater OE and RA EMG both before and during arm movement compared to those with less severe COPD and controls. Following exercise, OE and ES EMG increased in people with less severe COPD. This study shows that severe COPD is associated with impaired ability to recover balance and greater trunk muscle activity during postural challenges. Augmented trunk muscle activity may limit the contribution of trunk movements to balance recovery and could contribute to increased falls risk.

  6. Predicting chronic obstructive pulmonary disease hospitalizations based on concurrent influenza activity.

    PubMed

    Gerke, Alicia K; Tang, Fan; Yang, Ming; Foster, Eric D; Cavanaugh, Joseph E; Polgreen, Philip M

    2013-10-01

    Although influenza has been associated with chronic obstructive pulmonary disease (COPD) exacerbations, it is not clear the extent to which this association affects healthcare use in the United States. The first goal of this project was to determine to what extent the incidence of COPD hospitalizations is associated with seasonal influenza. Second, as a natural experiment, we used influenza activity to help predict COPD admissions during the 2009 H1N1 influenza pandemic. To do this, we identified all hospitalizations between 1998 and 2010 in the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP) during which a primary diagnosis of COPD was recorded. Separately, we identified all hospitalizations during which a diagnosis of influenza was recorded. We formulated time series regression models to investigate the association of monthly COPD admissions with influenza incidence. Finally, we applied these models, fit using 1998-2008 data, to forecast monthly COPD admissions during the 2009 pandemic. Based on time series regression models, a strong, significant association exists between concurrent influenza activity and incidence of COPD hospitalizations (p-value < 0.0001). The association is especially strong among older patients requiring mechanical ventilation. Use of influenza data to predict COPD admissions during the 2009 H1N1 pandemic reduced the mean-squared prediction error by 29.9%. We conclude that influenza activity is significantly associated with COPD hospitalizations in the United States and influenza activity can be exploited to more accurately forecast COPD admissions. Our results suggest that improvements in influenza surveillance, prevention, and treatment may decrease hospitalizations of patients diagnosed with COPD.

  7. Lupus pleuritis: a relevant risk factor for pulmonary tuberculosis.

    PubMed

    Pasoto, S G; Borba, E F; Bonfa, E; Shinjo, S K

    2010-12-01

    The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.

  8. Concurrent evaluation of microscopic observation of drug susceptibility assay for pulmonary and extrapulmonary tuberculosis

    PubMed Central

    Zadbuke, Sonali Sudhir; Set, Reena; Khan, Nishat; Shastri, Jayanthi

    2017-01-01

    BACKGROUND: Methods for detection and drug susceptibility of tuberculosis (TB) with solid media are inexpensive but slow and laborious. Rapid methods to diagnose TB and multidrug-resistant TB (MDR-TB) are a global priority for TB control. OBJECTIVES: A study was performed to compare the sensitivity of detection of mycobacterial growth and time of culture positivity by microscopic observation of drug susceptibility (MODS) assay with that of Lowenstein–Jensen (LJ) culture in pulmonary and extrapulmonary TB and to evaluate the concordance of the susceptibilities to isoniazid (INH) and rifampicin (RIF) by MODS and proportion method on LJ. MATERIALS AND METHODS: A prospective, laboratory-based study was conducted on a total of 300 samples from suspected cases of pulmonary and extrapulmonary TB. Samples were inoculated on LJ medium as per the standard guidelines and MODS assay was performed. RESULTS: Sensitivity of MODS assay was 80% and 83.3% and specificity was 92.9% and 83.3% for pulmonary and extrapulmonary samples, respectively. Difference between mean time to detection of Mycobacterium TB (MTB) by LJ medium and MODS was statistically significant, with MODS being faster. drug susceptibility testing (DST) by MODS when compared to economic variant of proportion method was 87.87% for RIF, 90.9% for INH, and 96.96% for MDR-TB detection. CONCLUSION: MODS assay provides rapid, safe, and sensitive detection of TB faster than the existing gold standard. It is extremely promising in effectively diagnosing MDR-TB. PMID:28367022

  9. MDR-TB Antibody Response (Western Blot) to Fractions of Isoniazid and Rifampicin Resistant Antigens of Mycobacterium tuberculosis.

    PubMed

    Hadizadeh Tasbiti, Alireza; Yari, Shamsi; Ghanei, Mostafa; Shokrgozar, Mohammad Ali; Bahrmand, Ahmadreza

    2015-12-01

    Drug-resistant TB poses a major threat to control of TB worldwide. Despite progress in the detection of Multidrug-resistant TB (MDR-TB) cases, a major diagnostic gap remains: 55% of reported TB patients estimated to have MDR-TB were not detected in 2013. MDR-TB antigens were conjugated to CNBr-activated Sepharose 4B. Specific polyclonal antibodies against MDR-TB Ags were prepared in rabbits using two boosted injections of the MDR-TB antigen. The antibodies were purified and treated with susceptible TB to remove any non-specific and cross-reactive antibodies. In the present study, comparative analysis of electrophoretic pattern of different antigens of INH/RIF-resistant TB were studied for identifying protein profiles. A RIF-resistant TB antigen was shown here to have different protein profiles from INH-resistant TB isolate. The results of Western blotting analysis showed that in the RIF- and INH-resistant antigenic fractions some bands of 14.4 and 45 kDa as immunogenic were common. Moreover, four bands of RIF-resistant TB antigen fractions (16, 19, 21, and 45 KDa) and one band of INH-resistant TB (about 26 KDa) were detected as diagnostic antigens. This study suggests that the Western blot is an accurate test to survey INH- and RIF-resistant TB antigens of M. tuberculosis infection. These findings indicate that MDR-TB diagnosis (based on Ag detection) could be useful in the identification of disease stages that precede symptomatic and microbiologically positive TB, such as subclinical and incipient TB.

  10. [Tuberculosis annual report 2009. Series 1. Summary of TB notification statistics in 2009].

    PubMed

    2011-02-01

    Annual reports of tuberculosis (TB) statistics in Japan have been compiled mainly using the output of the database obtained through the nationwide computerized tuberculosis surveillance system which has been operated since 1987. This system has been revised several times, with the latest revision conducted in 2007 when much new information was added. Therefore, a plan was drawn up to provide TB epidemiological statistics in Japan on "Kekkaku" and a series of ten reports was already issued as "TB Annual Report 2008". This is the first report of a new series for "TB Annual Report 2009". The report can be summarized as follows. The TB notification (incidence) rate fell below 20 per 100,000 in 2007 and continued to decline, reaching 19.0 in 2009. However, 24,170 TB patients were newly notified in 2009. For sputum smear positive pulmonary TB, the patient count was 9,675 with an incidence rate of 7.6 per 100,000 in 2009. Since June 2007, it has been legally compulsory to notify latent TB infections (LTBI) requiring treatment; the number in 2009 was 4119 cases.

  11. TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts

    PubMed Central

    Noguchi, Satoshi; Saito, Akira; Mikami, Yu; Urushiyama, Hirokazu; Horie, Masafumi; Matsuzaki, Hirotaka; Takeshima, Hideyuki; Makita, Kosuke; Miyashita, Naoya; Mitani, Akihisa; Jo, Taisuke; Yamauchi, Yasuhiro; Terasaki, Yasuhiro; Nagase, Takahide

    2017-01-01

    Transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz-heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments. TAZ was highly expressed in the fibroblastic foci of lungs from patients with IPF. TAZ controlled myofibroblast marker expression, proliferation, migration, and matrix contraction in cultured lung fibroblasts. Importantly, actin stress fibers and nuclear accumulation of TAZ were more evident when cultured on a stiff matrix, suggesting a feedback mechanism to accelerate fibrotic responses. Gene expression profiling revealed TAZ-mediated regulation of connective tissue growth factor (CTGF) and type I collagen. Clinical relevance of TAZ-regulated gene signature was further assessed using publicly available transcriptome data. These findings suggest that TAZ is involved in the pathogenesis of IPF through multifaceted effects on lung fibroblasts. PMID:28195168

  12. Persisting PET-CT lesion activity and M. tuberculosis mRNA after pulmonary tuberculosis cure

    PubMed Central

    Malherbe, Stephanus T.; Shenai, Shubhada; Ronacher, Katharina; Loxton, Andre G.; Dolganov, Gregory; Kriel, Magdalena; Van, Tran; Chen, Ray Y.; Warwick, James; Via, Laura E.; Song, Taeksun; Lee, Myungsun; Schoolnik, Gary; Tromp, Gerard; Alland, David; Barry, Clifton E.; Winter, Jill; Walzl, Gerhard

    2016-01-01

    The absence of a gold standard to determine when antibiotics have induced sterilizing cure confounds the development of new approaches to treat pulmonary tuberculosis (PTB). We detected PET-CT imaging response patterns consistent with active disease along with the presence of Mycobacterium tuberculosis mRNA in sputum and bronchoalveolar lavage samples in a substantial proportion of adult, HIV-negative PTB patients after standard 6-month treatment plus one year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of non-resolving and intensifying lesions on PET-CT might indicate ongoing transcription, suggesting that even apparently curative PTB treatment may not eradicate all organisms in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies and better treatment response markers are likely needed for the successful development of improved and shortened PTB treatment strategies. PMID:27595324

  13. Successful treatment of mobile right atrial thrombus and acute pulmonary embolism with intravenous tissue plasminogen activator

    PubMed Central

    Bajaj, R; Ramanakumar, Ajay; Mamidala, Suresh; Kumar, Deepti

    2013-01-01

    An 89-year-old woman came with symptoms of progressively worsening dyspnoea at rest over the preceding week. She was normotensive, had elevated jugular venous pressure and clear lungs. ECG revealed atrial fibrillation with the rapid ventricular rate. Labs were significant for markedly elevated pro-brain natriuretic peptide of 43 000 pg/mL and troponin-T of 1 ng/mL. An urgent 2D echocardiogram was obtained, which revealed the severely dilated right atrium and a large linear mobile mass in the right atrium consistent with a thrombus. An emergent CT scan revealed multiple bilateral pulmonary emboli. She received intravenous tissue plasminogen activator. Repeat echocardiogram performed 6 h later showed no evidence of the right atrial thrombus. She was subsequently maintained on intravenous heparin and transitioned to Coumadin. Early recognition of this rare but potentially fatal complication is important as prompt treatment measures can help in preventing life-threatening complications of the right atrial thrombus. PMID:23892824

  14. Pulmonary angiography

    MedlinePlus

    ... Pulmonary arteriography; Pulmonary angiogram; Angiogram of the lungs Images Pulmonary arteries References Jackson JE, Meaney JFM. Angiography. ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  15. Pulmonary Rehabilitation

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... people who have COPD (chronic obstructive pulmonary disease), sarcoidosis (sar-koy-DOE-sis), idiopathic pulmonary fibrosis , or ...

  16. Sputum Collection and Disposal Perceptions and Practices Among Pulmonary Tuberculosis Patients from Northern India

    PubMed Central

    Goyal, Vipin; Goel, Shewtank

    2016-01-01

    Introduction Even a single case of pulmonary Tuberculosis (TB) can infect many others. Hence, to ensure better control of the disease, it is imperative that all patients dispose their sputum safely. Outcomes of this study would highlight the gaps need to be bridged in order to curtail transmission of TB. Aim To analyse and ascertain perceptions about the disease and determine the sputum collection and disposal practices followed by sputum-positive TB patients. Materials and Methods In this cross-sectional study, 422 sputum-positive TB patients aged more than 15 years registered in the Tuberculosis Unit Ambala city from January 2012 – September 2012 formed the study population. After enrolment, at the end of one month, they were assessed for sputum collection and disposal practices by a trained person at their place of residences. Questionnaire was framed to collect relevant data. Results Safe sputum disposal was practised by 46.4% of the study subjects. More females than males disposed of sputum safely (70.4% vs. 29.6%), as did more subjects of low than middle socio-economic status (74.1% vs. 25.9%). 70.9% (n=66) of the subjects with a family history of TB practiced safe sputum disposal methods as compared to 39.5% (n=130) subjects without a family history of TB practiced the same. Similarly more literate than illiterate subjects (n=150, 57.5% vs. n=46, 28.6%) practiced safe sputum disposal methods. (p< 0.001). Regarding knowledge of causation of TB only 63% of the study subjects were in the view that this disease is caused by germs. Conclusion The study demonstrated that a large number of pulmonary TB patients practiced unsafe sputum disposal. Unsafe sputum disposal was higher among males, illiterate patients and those belonging to the lower socio-economic group. Therefore, it is need of the hour to launch Information, Education and Communication (IEC) activities so as to improve the sputum disposal practices among tuberculosis patients. PMID:28208887

  17. House dust mite potentiates capsaicin-evoked Ca2+ transients in mouse pulmonary sensory neurons via activation of protease-activated receptor-2.

    PubMed

    Gu, Qihai; Lee, Lu-Yuan

    2012-04-01

    House dust mite (HDM) is a major source of allergen in house dust and has been suggested to be involved in the pathogenesis of asthma. In this study, we aimed to investigate whether HDM can modulate the sensitivity of pulmonary sensory neurons and, if so, to elucidate the underlying mechanism. Fura-2-based ratiometric Ca(2+) imaging was carried out to determine the effect of HDM extract on the capsaicin-evoked Ca(2+) transient in mouse vagal pulmonary sensory neurons. Pretreatment with HDM (50 μg ml(-1), 5 min) significantly enhanced the Ca(2+) transient evoked by capsaicin in these neurons isolated from wild-type mice. This potentiating effect of HDM was not antagonized by E-64, a selective cysteine protease inhibitor, but was completely prevented by AEBSF, a specific serine protease inhibitor. In addition, the potentiating effect of HDM on capsaicin-evoked Ca(2+) transient was absent in the pulmonary sensory neurons isolated from protease-activated receptor-2 (PAR(2)) knockout mice. Furthermore, the sensitizing effect of HDM was completely abolished by U73122, a phosholipase C inhibitor, or chelerythrine, a protein kinase C inhibitor. In summary, our results demonstrate that HDM, mainly through its serine protease activity, potentiates capsaicin-evoked Ca(2+) transient in mouse pulmonary sensory neurons via the activation of PAR(2) and the phosholipase C-protein kinase C intracellular transduction cascade.

  18. Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function.

    PubMed

    Duong-Quy, S; Dao, P; Hua-Huy, T; Guilluy, C; Pacaud, P; Dinh-Xuan, A T

    2011-02-01

    Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function. Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought. Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls. Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.

  19. Tuberculosis of the manubriosternal joint and concurrent asymptomatic active pulmonary tuberculosis in a patient presenting with a chest wall mass.

    PubMed

    Gorospe, Luis; Ayala-Carbonero, Ana María; Rodríguez-Díaz, Ricardo; García Latorre, Raquel; Muñoz-Molina, Gemma María; Cabañero-Sánchez, Alberto

    2015-01-01

    A 62-year-old woman presented to our hospital with an anterior chest wall swelling. Computed tomography (CT) and magnetic resonance imaging showed findings consistent with an infectious arthritis of the manubriosternal joint, and CT images also demonstrated multiple centrilobular nodules in both lungs, suggesting an infectious bronchiolitis. A CT-guided fine needle aspiration of a presternal mass yielded growth of Mycobacterium tuberculosis. Bronchoalveolar lavage confirmed an active pulmonary tuberculosis. Septic arthritis of the manubriosternal joint is exceedingly rare.

  20. Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis.

    PubMed

    Xiao, Hong-Li; Li, Chun-Sheng; Zhao, Lian-Xing; Yang, Jun; Tong, Nan; An, Le; Liu, Qi-Tong

    2016-11-01

    Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.

  1. Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253

    PubMed Central

    Shiboski, C. H.; Chen, H.; Ghannoum, M. A.; Komarow, L.; Evans, S.; Mukherjee, P. K.; Isham, N.; Katzenstein, D.; Asmelash, A.; Omozoarhe, A. E.; Gengiah, S.; Allen, R.; Tripathy, S.; Swindells, S.

    2014-01-01

    SUMMARY OBJECTIVE To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. METHODS Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. RESULTS Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm3. Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2–4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22–48) and the specificity 85% (95%CI 81–88). CONCLUSION We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding. PMID:24903939

  2. Nebulized C1-Esterase Inhibitor does not Reduce Pulmonary Complement Activation in Rats with Severe Streptococcus Pneumoniae Pneumonia.

    PubMed

    de Beer, Friso; Lagrand, Wim; Glas, Gerie J; Beurskens, Charlotte J P; van Mierlo, Gerard; Wouters, Diana; Zeerleder, Sacha; Roelofs, Joris J T H; Juffermans, Nicole P; Horn, Janneke; Schultz, Marcus J

    2016-12-01

    Complement activation plays an important role in the pathogenesis of pneumonia. We hypothesized that inhibition of the complement system in the lungs by repeated treatment with nebulized plasma-derived human C1-esterase inhibitor reduces pulmonary complement activation and subsequently attenuates lung injury and lung inflammation. This was investigated in a rat model of severe Streptococcus pneumoniae pneumonia. Rats were intra-tracheally challenged with S. pneumoniae to induce pneumonia. Nebulized C1-esterase inhibitor or saline (control animals) was repeatedly administered to rats, 30 min before induction of pneumonia and every 6 h thereafter. Rats were sacrificed 20 or 40 h after inoculation with bacteria. Brochoalveolar lavage fluid and lung tissue were obtained for measuring levels of complement activation (C4b/c), lung injury and inflammation. Induction of pneumonia was associated with pulmonary complement activation (C4b/c at 20 h 1.24 % [0.56-2.59] and at 40 h 2.08 % [0.98-5.12], compared to 0.50 % [0.07-0.59] and 0.03 % [0.03-0.03] in the healthy control animals). The functional fraction of C1-INH was detectable in BALF, but no effect was found on pulmonary complement activation (C4b/c at 20 h 0.73 % [0.16-1.93] and at 40 h 2.38 % [0.54-4.19]). Twenty hours after inoculation, nebulized C1-esterase inhibitor treatment reduced total histology score, but this effect was no longer seen at 40 h. Nebulized C1-esterase inhibitor did not affect other markers of lung injury or lung inflammation. In this negative experimental animal study, severe S. pneumoniae pneumonia in rats is associated with pulmonary complement activation. Repeated treatment with nebulized C1-esterase inhibitor, although successfully delivered to the lungs, does not affect pulmonary complement activation, lung inflammation or lung injury.

  3. Verbal autopsy-assigned causes of death among adults being investigated for TB in South Africa

    PubMed Central

    Maraba, Noriah; Karat, Aaron S; McCarthy, Kerrigan; Churchyard, Gavin J; Charalambous, Salome; Kahn, Kathleen; Grant, Alison D; Chihota, Violet

    2016-01-01

    Background Adults being investigated for TB in South Africa experience high mortality, yet causes of death (CoD) are not well defined. We determined CoD in this population using verbal autopsy (VA), and compared HIV- and TB-associated CoD using physician-certified verbal autopsy (PCVA) and InterVA-4 software. Methods All contactable consenting caregivers of participants who died during a trial comparing Xpert MTB/RIF to smear microscopy were interviewed using the WHO VA tool. CoD were assigned using PCVA and InterVA-4. Kappa statistic (K) and concordance correlation coefficient (CCC) were calculated for comparison. Results Among 231 deaths, relatives of 137 deceased were interviewed. Of the 137 deceased 76 (55.4%) were males, median age 41 years (IQR 33–50). PCVA assigned 70 (51.1%) TB immediate CoD (44 [62.8%] pulmonary TB; 26 [37.1%] extra-pulmonary TB); 21 (15.3%) HIV/AIDS-related; and 46 (33.5%) other CoD. InterVA-4 assigned 48 (35.0%) TB deaths; 49 (35.7%) HIV/AIDS-related deaths; and 40 (29.1%) other CoD. Agreement between PCVA and InterVA-4 CoD was slight at individual level (K=0.20; 95% CI 0.10–0.30) and poor at population level (CCC 0.67; 95% CI 0.38–0.99). Conclusions TB and HIV are leading CoD among adults being investigated for TB. PCVA and InterVA agreement at individual level was slight and poor at population level. VA methodology needs further development where TB and HIV are common. PMID:27794093

  4. Activation of bitter taste receptors in pulmonary nociceptors sensitizes TRPV1 channels through the PLC and PKC signaling pathway.

    PubMed

    Gu, Qihai David; Joe, Deanna S; Gilbert, Carolyn A

    2017-03-01

    Bitter taste receptors (T2Rs), a G protein-coupled receptor family capable of detecting numerous bitter-tasting compounds, have recently been shown to be expressed and play diverse roles in many extraoral tissues. Here we report the functional expression of T2Rs in rat pulmonary sensory neurons. In anesthetized spontaneously breathing rats, intratracheal instillation of T2R agonist chloroquine (10 mM, 0.1 ml) significantly augmented chemoreflexes evoked by right-atrial injection of capsaicin, a specific activator for transient receptor potential vanilloid receptor 1 (TRPV1), whereas intravenous infusion of chloroquine failed to significantly affect capsaicin-evoked reflexes. In patch-clamp recordings with isolated rat vagal pulmonary sensory neurons, pretreatment with chloroquine (1-1,000 µM, 90 s) concentration dependently potentiated capsaicin-induced TRPV1-mediated inward currents. Preincubating with diphenitol and denatonium (1 mM, 90 s), two other T2R activators, also enhanced capsaicin currents in these neurons but to a lesser extent. The sensitizing effect of chloroquine was effectively prevented by the phospholipase C inhibitor U73122 (1 µM) or by the protein kinase C inhibitor chelerythrine (10 µM). In summary, our study showed that activation of T2Rs augments capsaicin-evoked TRPV1 responses in rat pulmonary nociceptors through the phospholipase C and protein kinase C signaling pathway.

  5. Angiogenic activity of sera from extrinsic allergic alveolitis patients in relation to clinical, radiological, and functional pulmonary changes.

    PubMed

    Zielonka, Tadeusz M; Demkow, Urszula; Filewska, Małgorzata; Bialas, Beata; Zycinska, Katarzyna; Radzikowska, Elzbieta; Wardyn, Andrzej K; Skopinska-Rozewska, Ewa

    2010-10-01

    Extrinsic allergic alveolitis (EAA) caused by inhaled organic environmental allergens can progress to a fibrotic end-stage lung disease. Neovascularization plays an important role in pathogenesis of pulmonary fibrosis. The aim of this study was to assess the effect of sera from EAA patients on the angiogenic capability of normal peripheral human mononuclear cells (MNC) in relation to the clinical, radiological, and functional changes. The study population consisted of 30 EAA patients and 16 healthy volunteers. Routine pulmonary function tests were undertaken using ERS standards. As an angiogenic test, leukocyte-induced angiogenesis assay according to Sidky and Auerbach was used. Compared with sera from healthy volunteers, sera from our EAA patients significantly stimulated angiogenesis (P < 0.001). However, sera from healthy donors also stimulated angiogenesis compared to PBS (P < 0.001). No correlation was found between serum angiogenic activity and clinical symptoms manifested by evaluated patients. A decrease in DLco and in lung compliance in EAA patients was observed but no significant correlation between pulmonary functional tests and serum angiogenic activity measured by the number of microvessels or an angiogenesis index was found. However, the proangiogenic effect of sera from EAA patients differed depending on the stage of the disease and was stronger in patients with fibrotic changes. The present study suggests that angiogenesis plays a role in the pathogenesis of EAA. It could be possible that the increase in the angiogenic activity of sera from EAA patients depends on the phase of the disease.

  6. Prevalence of Pulmonary Tuberculosis among Prison Inmates in Ethiopia, a Cross-Sectional Study

    PubMed Central

    Ali, Solomon; Haileamlak, Abraham; Wieser, Andreas; Pritsch, Michael; Heinrich, Norbert; Loscher, Thomas; Hoelscher, Michael; Rachow, Andrea

    2015-01-01

    Setting Tuberculosis (TB) is one of the major health problems in prisons. Objective This study was done to assess the prevalence and determinants of active tuberculosis in Ethiopian prisons. Design A cross-sectional study was conducted from January 2013 to December 2013 in 13 zonal prisons. All incarcerated inmates underwent TB symptom screening according to WHO criteria. From identified TB-suspects two sputum samples were analyzed using smear microscopy and solid culture. A standardized questionnaire assessing TB risk factors was completed for each TB suspect. Results 765 (4.9%) TB suspects were identified among 15,495 inmates. 51 suspects were already on anti-TB treatment (6.67%) and 20 (2.8%) new culture-confirmed TB cases were identified in the study, resulting in an overall TB prevalence of 458.1/100,000 (95%CI: 350-560/100,000). Risk factors for active TB were alcohol consumption, contact with a TB case before incarceration and no window in prison cell. HIV prevalence was not different between TB suspects and active TB cases. Further, the TB burden in prisons increased with advancing distance from the capital Addis Ababa. Conclusions The overall TB prevalence in Ethiopian prisons was high and extremely variable among different prisons. TB risk factors related to conditions of prison facilities and the impact of implemented TB control measures need to be further studied in order to improve TB control among inmates. PMID:26641654

  7. NO Hyperpolarizes Pulmonary Artery Smooth Muscle Cells and Decreases the Intracellular Ca2+ Concentration by Activating Voltage-Gated K+ Channels

    NASA Astrophysics Data System (ADS)

    Yuan, Xiao-Jian; Tod, Mary L.; Rubin, Lewis J.; Blaustein, Mordecai P.

    1996-09-01

    NO causes pulmonary vasodilation in patients with pulmonary hypertension. In pulmonary arterial smooth muscle cells, the activity of voltage-gated K+ (KV) channels controls resting membrane potential. In turn, membrane potential is an important regulator of the intracellular free calcium concentration ([Ca2+]i) and pulmonary vascular tone. We used patch clamp methods to determine whether the NO-induced pulmonary vasodilation is mediated by activation of KV channels. Quantitative fluorescence microscopy was employed to test the effect of NO on the depolarization-induced rise in [Ca2+]i. Blockade of KV channels by 4-aminopyridine (5 mM) depolarized pulmonary artery myocytes to threshold for initiation of Ca2+ action potentials, and thereby increased [Ca2+]i. NO (≈ 3 μ M) and the NO-generating compound sodium nitroprusside (5-10 μ M) opened KV channels in rat pulmonary artery smooth muscle cells. The enhanced K+ currents then hyperpolarized the cells, and blocked Ca2+-dependent action potentials, thereby preventing the evoked increases in [Ca2+]i. Nitroprusside also increased the probability of KV channel opening in excised, outside-out membrane patches. This raises the possibility that NO may act either directly on the channel protein or on a closely associated molecule rather than via soluble guanylate cyclase. In isolated pulmonary arteries, 4-aminopyridine significantly inhibited NO-induced relaxation. We conclude that NO promotes the opening of KV channels in pulmonary arterial smooth muscle cells. The resulting membrane hyperpolarization, which lowers [Ca2+]i, is apparently one of the mechanisms by which NO induces pulmonary vasodilation.

  8. Diaphragm efficiency estimated as power output relative to activation in chronic obstructive pulmonary disease.

    PubMed

    Finucane, Kevin E; Singh, Bhajan

    2012-11-01

    Muscle efficiency increases with fiber length and decreases with load. Diaphragm efficiency (Eff(di)) in healthy humans, measured as power output (Wdi) relative to the root mean square of diaphragm electromyogram (RMS(di)), increases with hyperpnea due to phasic activity of abdominal muscles acting to increase diaphragm length at end expiration (L(di ee)) and decrease inspiratory load. In chronic obstructive pulmonary disease (COPD), hyperpnea may decrease Eff(di) if L(di ee) decreases and load increases due to airflow obstruction and dynamic hyperinflation. To examine this hypothesis, we measured Eff(di) in six COPD subjects (mean forced expiratory volume in 1 s: 54% predicted) when breathing air and at intervals during progressive hypercapnic hyperpnea. Wdi was measured as the product of mean inspiratory transdiaphragmatic pressure (ΔPdi(mean)), diaphragm tidal volume measured fluoroscopically, and 1/inspiratory duration. Results were compared with those of six healthy subjects reported previously. In COPD, L(di ee) was normal when breathing air. ΔPdi(mean) and Wdi increased normally, and RMS(di) increased disproportionately (P = 0.01) with hyperpnea, and, unlike health, inspiratory capacity (IC), L(di ee), and Eff(di) did not increase. IC and L(di ee) were constant with hyperpnea because mean expiratory flow increased as expiratory duration decreased (r(2) = 0.65), and because expiratory flow was terminated actively by the balance between expiratory and inspiratory muscle forces near end expiration, and these forces increased proportionately with hyperpnea (r(2) = 0.49). At maximum ventilation, diaphragm radius of curvature at end inspiration increased in COPD (P = 0.04) but not controls; diaphragm radius of curvature at end inspiration and ln(Eff(di)) were negatively correlated (P = 0.01). Thus in COPD with modest airflow obstruction, Eff(di) did not increase normally with hyperpnea due to a constant L(di ee) and inspiratory flattening of the diaphragm.

  9. Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types.

    PubMed

    Falach, Reut; Sapoznikov, Anita; Gal, Yoav; Israeli, Ofir; Leitner, Moshe; Seliger, Nehama; Ehrlich, Sharon; Kronman, Chanoch; Sabo, Tamar

    2016-09-06

    The plant-derived toxins ricin and abrin, operate by site-specific depurination of ribosomes, which in turn leads to protein synthesis arrest. The clinical manifestation following pulmonary exposure to these toxins is that of a severe lung inflammation and respiratory insufficiency. Deciphering the pathways mediating between the catalytic activity and the developing lung inflammation, requires a quantitative appreciation of the catalytic activity of the toxins, in-vivo. In the present study, we monitored truncated cDNA molecules which are formed by reverse transcription when a depurinated 28S rRNA serves as template. We found that maximal depurination after intranasal exposure of mice to 2LD50 ricin was reached 48h, where nearly 40% of the ribosomes have been depurinated and that depurination can be halted by post-exposure administration of anti-ricin antibodies. We next demonstrated that the effect of ricin intoxication on different cell types populating the lungs differs greatly, and that outstandingly high levels of damage (80% depurination), were observed in particular for pulmonary epithelial cells. Finally, we found that the magnitude of depurination induced by the related plant-derived toxin abrin, was significantly lower in comparison to ricin, and can be attributed mostly to reduced depurination of pulmonary epithelial cells by abrin. This study provides for the first time vital information regarding the scope and timing of the catalytic performance of ricin and abrin in the lungs of intact animals.

  10. In vivo and in vitro correlation of pulmonary MAP kinase activation following metallic exposure.

    PubMed

    Silbajoris, R; Ghio, A J; Samet, J M; Jaskot, R; Dreher, K L; Brighton, L E

    2000-06-01

    Residual oil fly ash (ROFA) is a particulate pollutant produced in the combustion of fuel oil. Exposure to ROFA is associated with adverse respiratory effects in humans, induces lung inflammation in animals, and induces inflammatory mediator expression in cultured human airway epithelial cells (HAEC). ROFA has a high content of transition metals, including vanadium, a potent tyrosine phosphatase inhibitor that we have previously shown to disregulate phosphotyrosine metabolism and activate mitogen-activated protein kinase (MAPK) signaling cascades in HAEC. In order to study MAPK activation in response to in vivo metal exposure, we used immunohistochemical methods to detect levels of phosphorylated protein tyrosines (P-Tyr) and the MAPKs ERK1/2, JNK, and P38 in lung sections from rats intratracheally exposed to ROFA. After a 1-h exposure to 500 microg ROFA, rat lungs showed no histological changes and no significant increases in immunostaining for either P-Tyr or phospho-(P-) MAPKs compared to saline-instilled controls. At 4 h of exposure, there was mild and variable inflammation in the lung, which was accompanied by an increase in specific immunostaining for P-Tyr and P-MAPKs in airway and alveolar epithelial cells and resident macrophages. By 24 h of exposure, there was a pronounced inflammatory response to ROFA instillation and a marked increase in levels of P-Tyr and P-MAPKs present within the alveolar epithelium and in the inflammatory cells, while the airway epithelium showed a continued increase in the expression of P-ERK1/2. By comparison, HAEC cultures exposed to 100 microg/ml ROFA for 20 min resulted in marked increases in P-Tyr and P-MAPKs, which persisted after 24 h of exposure. P-Tyr levels continued to accumulate for up to 24 h in HAEC exposed to ROFA. These results demonstrate in vivo activation in cell signaling pathways in response to pulmonary exposure to particulate matter, and support the relevance of in vitro studies in the identification of

  11. Accelerated Dosing Frequency of a Pulmonary Formulation of Tissue Plasminogen Activator is Well-Tolerated in Mice

    PubMed Central

    Stringer, Kathleen A; Tobias, Meghan; Dunn, John S; Campos, Jackie; Van Rheen, Zachary; Mosharraf, Mitra; Nayar, Rajiv

    2009-01-01

    Summary Tissue plasminogen activator (tPA) has both fibrinolytic and anti-inflammatory activity. These properties may be useful in treating inflammatory lung diseases, such as acute respiratory distress syndrome (ARDS). We have previously demonstrated the feasibility of targeted pulmonary delivery of tPA. As part of our research to develop a clinically viable pulmonary formulation of tPA, we assessed the tolerability and incidence of haemorrhage associated with the administration of a pulmonary formulation of mouse tPA (pf-mtPA). Intratracheal doses of nebulized pf-mtPA or sterile saline were administered with increasing frequency to male and female B6C3F1 mice. After dosing, the mice entered a recovery period, after which they were killed and their lungs were lavaged and harvested. Post-mortem gross necropsy was performed and all major organs were assessed histologically for haemorrhage. The bronchoalveolar lavage fluid was assessed for markers of lung injury. Mouse tPA that was formulated to mimic a previously characterized human pf-tPA was well tolerated when given intratracheally with increasing dosing frequency. The administration of pf-mtPA did not result in any detectable haemorrhagic-related events or signs of lung injury. The results of the present longitudinal study demonstrate that a maximally feasible dose of pf-mtPA (3 mg/kg) can be given frequently over a short period of time (12 h) without haemorrhagic complications. Although these data were generated in a healthy mouse model, they provide support for the continued evaluation of pf-tPA for the treatment of pulmonary diseases, such as ARDS. PMID:18671720

  12. Chronic left atrial volume overload abbreviates the action potential duration of the canine pulmonary vein myocardium via activation of IK channel.

    PubMed

    Nouchi, Hideaki; Takahara, Akira; Nakamura, Hideki; Namekata, Iyuki; Sugimoto, Takahiko; Tsuneoka, Yayoi; Takeda, Kiyoshi; Tanaka, Toshikazu; Shigenobu, Koki; Sugiyama, Atsushi; Tanaka, Hikaru

    2008-11-12

    Electrophysiological properties of the pulmonary vein myocardium were assessed in a canine chronic atrioventricular block model resulting in left atrial volume overload. Five chronic atrioventricular block dogs and five sham-operated dogs were used. The heart was removed two months after a surgical procedure causing atrioventricular block, when atrial structural remodeling was established. Standard microelectrode penetrations were made with glass microelectrodes to obtain action potential signals of left atrium and pulmonary vein myocardia. The resting membrane potential in the pulmonary vein was more positive than that in the left atrium (-69 mV vs -74 mV) in both animal groups. The action potential duration at 50% repolarization of the pulmonary vein was shorter in the chronic atrioventricular block dogs than in the sham-operated dogs (38 ms vs 63 ms), whereas no significant difference was detected in the action potential duration of the left atrium between the two animal groups (67 ms vs 61 ms). The action potential duration of the pulmonary vein in the chronic atrioventricular block dogs was prolonged by charybdotoxin but not by iberiotoxin. Such prolongation was not observed in the normal pulmonary vein. These results suggest that long-term left atrial dilatation shortened the action potential duration of pulmonary vein myocardium, which may be associated with activation of the intermediate conductance Ca2+-activated K+ channel (IK channel).

  13. Mtb-Specific CD27low CD4 T Cells as Markers of Lung Tissue Destruction during Pulmonary Tuberculosis in Humans

    PubMed Central

    Nikitina, Irina Yu; Kondratuk, Natalya A.; Kosmiadi, George A.; Amansahedov, Rasul B.

    2012-01-01

    Background Effector CD4 T cells represent a key component of the host’s anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection. Methodology/Principal Findings The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27low cells within a population of Mtb- specific CD4 T lymphocytes (“CD27lowIFN-γ+” cells). The percentages of CD27lowIFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27lowIFN-γ+ cells were uniformly high in the lungs (>76%), but varied in blood (12–92%). The major correlate for the accumulation of CD27lowIFN-γ+ cells in blood was lung destruction (r = 0.65, p = 2.7×10−7). A cutoff of 47% of CD27lowIFN-γ+ cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27lowIFN-γ+cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01). Conclusions Highly differentiated CD27low Mtb-specific (CD27lowIFN-γ+) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27lowIFN-γ+ cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell

  14. Properties of a novel K+ current that is active at resting potential in rabbit pulmonary artery smooth muscle cells.

    PubMed Central

    Evans, A M; Osipenko, O N; Gurney, A M

    1996-01-01

    1. An outward current (IK(N)) was identified in rabbit pulmonary artery myocytes, which persisted after Ca(2+)-activated and ATP-sensitive K+ currents were blocked by TEA (10 mM) and glibenclamide (10 microM), respectively, and after A-like (IK(A)) and delayed rectifer (IK(V)) K+ currents were inactivated by clamping the cell at 0 mV for 10 min. It was found in smooth muscle cells at all levels of the pulmonary arterial tree. 2. The relationship between the reversal potential of IK(N) and the extracellular K+ concentration ([K+]o) was close to that expected for a K(+)-selective channel. Deviation from Nernstian behaviour at low [K+)o could be accounted for by the presence of an accompanying leakage current. 3. IK(N) is voltage gated. It has a low threshold for activation, between -80 and -65 mV, and activates slowly without delay. Activation follows an exponential time course with a time constant of 1.6 s at -60 mV. Deactivation is an order of magnitude faster than activation, with a time constant of 107 ms at -60 mV. 4. IK(N) showed a similar sensitivity to 4-aminopyridine as IK(A) and IK(V), with 49% inhibition at 10 mM. The current was not blocked by microM quinine, which did inhibit IK(A) and IK(V), by 51 and 47%, respectively. 5. Activation of IK(N) was detected at potentials close to the resting membrane potential of pulmonary artery smooth muscle cells, under physiological conditions. Thus it is likely to contribute to the resting membrane potential of these cells. PMID:8910225

  15. Antioxidant enzyme activities and mitochondrial fatty acids in pulmonary hypertension syndrome (PHS) in broilers.

    PubMed

    Iqbal, M; Cawthon, D; Beers, K; Wideman, R F; Bottje, W G

    2002-02-01

    Major objectives of this study were to assess antioxidant protection and fatty acid profile in lung mitochondria and whole liver in broilers with pulmonary hypertension syndrome [(PHS; with and without high dietary vitamin E (VE)] (Experiment 1) and in broilers that did not develop PHS but were genetically selected (S) or not selected (NS) for resistance to PHS (Experiment 2). In Experiment 1, lung mitochondrial glutathione peroxidase (GSH-Px) activity was elevated in broilers with PHS compared to controls, broilers fed high VE, and broilers fed high VE with PHS (VE-PHS), but there were no differences in GSH reductase (GSH-Rd) among groups. In liver tissue, GSH-Px was also elevated by PHS but was lower in VE and VE-PHS groups than in controls. There were no differences in liver GSH-Rd, superoxide dismutase (SOD), or gamma-glutamylcysteine synthetase (gamma-GCS) activities with the exception that gamma-GCS was higher in the VE-PHS group than in the other groups. In Experiment 2, S lung mitochondria exhibited lower GSH-Px and higher GSH-Rd compared to NS broilers. In the liver, there were no differences in GSH-Px, GSH-Rd, or gamma-GCS, but SOD was lower in S compared to the NS broilers. High VE increased the percentage of saturated fatty acids and decreased the percentage of unsaturated fatty acids in lung mitochondria in Experiment 1; there were no differences in fatty acid content between S and NS mitochondria in Experiment 2. Thus, it appears that GSH recycling enzyme activities are affected by PHS and high VE presumably in response to differences in oxidative stress and that genetic resistance to PHS is associated with an inherently better capability to metabolize oxidants in lung mitochondria. The increase in saturation of lung mitochondrial fatty acids with high dietary VE would presumably make them more resistant to oxidative stress and, thus, reduce the level of PHS-induced oxidative stress.

  16. Efficacy of an mHealth intervention to stimulate physical activity in COPD patients after pulmonary rehabilitation.

    PubMed

    Vorrink, Sigrid N W; Kort, Helianthe S M; Troosters, Thierry; Zanen, Pieter; Lammers, Jan-Willem J

    2016-10-01

    Physical inactivity in patients with chronic obstructive pulmonary disease (COPD) is associated with poor health status and increased disease burden. The present study aims to test the efficacy of a previously developed mobile (m)Health intervention to improve or maintain physical activity in patients with COPD after pulmonary rehabilitation.A randomised controlled trial was performed in 32 physiotherapy practices in the Netherlands. COPD patients were randomised into intervention or usual care groups. The intervention consisted of a smartphone application for the patients and a monitoring website for the physiotherapists. Measurements were performed at 0, 3, 6 and 12 months. Physical activity, functional exercise capacity, lung function, health-related quality of life and body mass index were assessed.157 patients started the study and 121 completed it. There were no significant positive effects of the intervention on physical activity (at 0 months: intervention 5824±3418 steps per weekday, usual care 5717±2870 steps per weekday; at 12 months: intervention 4819±2526 steps per weekday, usual care 4950±2634 steps per weekday; p=0.811) or on the secondary end-points. There was a significant decrease over time in physical activity (p<0.001), lung function (p<0.001) and mastery (p=0.017), but not in functional exercise capacity (p=0.585).Although functional exercise capacity did not deteriorate, our mHealth intervention did not improve or maintain physical activity in patients with COPD after a period of pulmonary rehabilitation.

  17. Accuracy of a new rapid antigen detection test for pulmonary tuberculosis

    PubMed Central

    Aliannejad, Rasoul; Bahrmand, Ahmadreza; Abtahi, Hamidreza; Seifi, Mahnaz; Safavi, Enayat; Abdolrahimi, Farid; Shahriaran, Shahriyar

    2016-01-01

    Background and Objectives: Tuberculosis (TB) is a major problem in the world. Treatment and control of TB needs detection of the Mycobacterium tuberculosis (MT) in the proper samples. While smear doesn’t have enough sensitivity, culture and PCR are expensive, time consuming and unavailable in many centers. Recent development of a rapid TB antigen detection test (PrTBK) at Pasteur Institute of Iran could give a simple way for diagnosis of TB in about two hours. In this test the antigen-antibody complex will change color when gold conjugated mouse anti-rabbit antibody detects specific MT cell wall antigen in suspected samples. Materials and Methods: We evaluated the diagnostic accuracy of PrTBK for diagnosis of pulmonary TB in comparison with smear, culture and PCR techniques in 56 consecutive samples (47 BAL and 13 sputum samples) obtained from patients with clinical suspicion of active TB. Results: Twentynine patients (52%) were female and seven patients were HIV positive. PrTBK was positive in 17 culture positive and 4 culture negative samples (100% sensitivity, 89% specificity and 92% accuracy in comparison with culture method). In two out of four patients with negative culture who were positive for PrTBK, PCR and anti-tuberculosis drugs trial therapy responses were in favor of tuberculosis. If we take this finding into account, the accuracy of PrTBK will rise. Conclusion: High sensitivity and accuracy of PrTBK test enable us to initiate treatment on the basis of this convenient and rapid test. PMID:28210462

  18. Cost-effectiveness of active case-finding of household contacts of pulmonary tuberculosis patients in a low HIV, tuberculosis-endemic urban area of Lima, Peru.

    PubMed

    Shah, L; Rojas, M; Mori, O; Zamudio, C; Kaufman, J S; Otero, L; Gotuzzo, E; Seas, C; Brewer, T F

    2017-04-01

    We compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.

  19. A review of the literature on the economics of vaccination against TB.

    PubMed

    Tu, Hong-Anh T; Vu, Hoa D; Rozenbaum, Mark H; Woerdenbag, Herman J; Postma, Maarten J

    2012-03-01

    The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

  20. Influence of old pulmonary tuberculosis on the management of secondary spontaneous pneumothorax in patients over the age of 70 years

    PubMed Central

    Lee, Sang Cjeol

    2016-01-01

    Background This study aimed to investigate the treatment outcomes and influence of old pulmonary tuberculosis (TB) in elderly patients (over 70 years) with secondary spontaneous pneumothorax (SSP). Methods A retrospective analysis was performed on patients with SSP between January 2002 and December 2014. Treatment outcomes including chest tube duration (CTD), type and complication of surgery, recurrence and survival rate were obtained from the review of medical records and analyzed statistically. Results Two hundred and sixteen consecutive cases were recruited. Of these, 134 (62.0%) did not have old pulmonary TB [non-tuberculosis (NTB) group], and the other 82 (38.0%) had experienced pulmonary TB (TB group). More thoracoscopic surgeries had been performed in the NTB group (P=0.038). More postoperative complications developed in the TB group (P=0.038). Total CTD and postoperative CTD in the TB group were significantly longer (P=0.015 and 0.030, respectively). However, recurrence-free survival and overall survival rate were not significantly different between the TB and NTB groups. Conclusions Old pulmonary TB in elderly patients with SSP made their treatment more complicated. However, surgery might be considered in highly selected patients regardless of old pulmonary TB, and could be conducted with acceptable morbidity and mortality. PMID:27867567

  1. Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.

    PubMed

    Wlaź, Piotr; Knaga, Sebastian; Kasperek, Kornel; Wlaź, Aleksandra; Poleszak, Ewa; Jeżewska-Witkowska, Grażyna; Winiarczyk, Stanisław; Wyska, Elżbieta; Heinekamp, Thorsten; Rundfeldt, Chris

    2015-08-01

    Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.

  2. Bone marrow mesenchymal stem cells protect against bleomycin-induced pulmonary fibrosis in rat by activating Nrf2 signaling

    PubMed Central

    Ni, Shirong; Wang, Dexuan; Qiu, Xiaoxiao; Pang, Lingxia; Song, Zhangjuan; Guo, Kunyuan

    2015-01-01

    Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. In the present study, we investigated bone marrow mesenchymal stem cells (BMSCs) for the treatment of bleomycin-induced pulmonary fibrosis. Our results showed that BMSCs administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. The gene expression levels of NAD(P)H: quinine oxidoreductase 1 (NQO1), gama-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), attenuated by bleomycin, were increased up to basal levels after BMSCs transplantation. BMSCs significantly increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) production in the injured lung. The present study provides evidence that BMSCs may be a potential therapeutic reagent for the treatment of lung fibrosis. PMID:26339340

  3. Sequential analysis of myofibroblast differentiation and transforming growth factor-β1/Smad pathway activation in murine pulmonary fibrosis.

    PubMed

    Usuki, Jiro; Matsuda, Kuniko; Azuma, Arata; Kudoh, Shoji; Gemma, Akihiko

    2012-01-01

    Myofibroblasts play a critical role in tissue fibrosis. However, the intracellular signaling pathways in myofibroblast differentiation are poorly understood. Here, we studied the relationship between transforming growth factor-β (TGF-β)/Smad pathway activation and myofibroblast differentiation in both in vivo and in vitro experiments. In murine bleomycin-induced pulmonary fibrosis, nuclear localization of phosphorylated Smad2/3 (p-Smad2/3) was observed in pulmonary fibrotic lesions 7 days after bleomycin injection, whereas α-smooth muscle actin (ASMA)-positive myofibroblasts appeared in the lesions at 14 days, when the cytoplasmic localization of p-Smad2/3 was observed. We also compared the effects of TGF-β1 on myofibroblast differentiation and on type I collagen expression in a murine lung fibroblast cell line (MLg2908). TGF-β1 induced rapid expression of p-Smad2/3 in nuclei, after which ASMA organization in the cytoplasm of fibroblasts was observed. However, TGF-β1 produced no effect on the quantity of ASMA, either in mRNA levels or protein levels, even after the phosphorylation of Smad2/3. In contrast, TGF-β1 upregulated the expression of type I collagen mRNA. These findings suggest that in pulmonary fibrosis the molecular mechanism of myofibroblast differentiation is complex and that the difference between ASMA expression and type I collagen expression is mediated by the TGF-β/Smad pathway.

  4. New tests will improve detection of latent TB.

    PubMed

    Chapman, Ann L N

    2011-11-01

    In the UK cases of active TB have risen substantially over the past 20 years. This increase has occurred almost exclusively in individuals born outside the UK, who now constitute more than two-thirds of cases. Only around one in ten people who are infected will develop active disease. The remaining 90% are presumed to have latent TB infection (LTBI) where viable mycobacteria are thought to persist for decades, and may reactivate if the host's immune system is weakened. In a country such as the UK with a low incidence of TB, a high proportion of cases result from reactivation of latent TB, rather than transmission by infectious cases. In the past 10 years a novel type of diagnostic test for LTBI has been developed: the interferon-gamma release assays (IGRA). Their major advantage over the tuberculin skin test is that they are not affected by prior BCG vaccination and they have a specificity of well over 90%. These tests are unable to distinguish between active and latent TB infection: this distinction must be performed purely on clinical grounds. Patients with a positive test should be assessed by a clinician with expertise in TB to ensure an appropriate management plan for each patient. The role of IGRAs in diagnosis of active TB is limited since in a patient with suspected active TB a positive result may indicate LTBI in combination with an alternative diagnosis. At a population level screening and chemoprophylaxis contributes usefully to TB control. However, only those under 35 with LTBI should receive prophylaxis. After this age the increasing risks of hepatotoxicity begin to outweigh the diminishing benefits of prophylaxis. The exceptions are healthcare workers, where the benefits are not just to the individual but also extend to their patients, and immunocompromised patients. The IGRAs represent a major development in the diagnosis of LTBI. While currently most of their use is through established TB screening services, it is likely in future that they will

  5. Decreasing cost effectiveness of testing for latent TB in HIV in a low TB incidence area.

    PubMed

    Capocci, Santino; Smith, Colette; Morris, Stephen; Bhagani, Sanjay; Cropley, Ian; Abubakar, Ibrahim; Johnson, Margaret; Lipman, Marc

    2015-07-01

    Testing for latent tuberculosis infection (LTBI) in HIV-infected persons in low tuberculosis (TB) incidence areas is often recommended. Using contemporary, clinical data, we report the yield and cost-effectiveness of testing all HIV attendees, two current UK strategies and no LTBI testing. Economic modelling was performed utilising 10-year follow up data from a large HIV clinical cohort. Outcomes were numbers of cases of active TB and incremental cost per quality-adjusted life year (QALY) gained. Between 2000 and 2010, 256 people were treated for TB/HIV co-infection. 72 (28%) occurred ≥3 months after HIV diagnosis and may have been prevented by LTBI testing. Between 2000 and 2005, the incremental cost per QALY gained for the British HIV Association (BHIVA) and UK National Institute of Care Excellence (NICE) strategies, and testing all clinic attendees was €6270, €6998 and €33,473, respectively. These rose to €9332, €32,564 and €74,067, respectively, between 2005 and 2010. Probabilistic sensitivity analysis suggested that at a threshold of €24,000 per additional QALY, the most cost-effective strategies would be NICE or testing all in 2000-2005 and BHIVA during 2005-2010. Both UK testing regimens missed cases but are cost-effective compared with no testing. Using recent data, they all became more expensive, suggesting that alternative or more targeted TB testing strategies must be considered.

  6. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...

  7. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...

  8. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...

  9. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...

  10. IMPACT OF CIGARETTE SMOKING ON RATES AND CLINICAL PROGNOSIS OF PULMONARY TUBERCULOSIS IN SOUTHERN MEXICO

    PubMed Central

    Bonacci, Robert A.; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Reynales-Shigematsu, Luz Myriam; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Delgado-Sánchez, Guadalupe; Martínez-Gamboa, Rosa Areli; Cano-Arellano, Bulmaro; Sifuentes-Osornio, José; de León, Alfredo Ponce

    2012-01-01

    Objectives To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. Materials From 1995-2010, we analyzed data from 1062 patients with TB and from 2001-2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. Results Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS,17.74) smoker-nonsmoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. Conclusions Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies. PMID:22982014

  11. Temperature-dependent structure of Tb-doped magnetite nanoparticles

    SciTech Connect

    Rice, Katherine P.; Russek, Stephen E. Shaw, Justin M.; Usselman, Robert J.; Evarts, Eric R.; Silva, Thomas J.; Nembach, Hans T.; Geiss, Roy H.; Arenholz, Elke; Idzerda, Yves U.

    2015-02-09

    High quality 5 nm cubic Tb-doped magnetite nanoparticles have been synthesized by a wet-chemical method to investigate tailoring of magnetic properties for imaging and biomedical applications. We show that the Tb is incorporated into the octahedral 3+ sites. High-angle annular dark-field microscopy shows that the dopant is well-distributed throughout the particle, and x-ray diffraction measurements show a small lattice parameter shift with the inclusion of a rare-earth dopant. Magnetization and x-ray magnetic circular dichroism data indicate that the Tb spins are unpolarized and weakly coupled to the iron spin lattice at room temperature, and begin to polarize and couple to the iron oxide lattice at temperatures below 50 K. Broadband ferromagnetic resonance measurements show no increase in magnetic damping at room temperature for Tb-doped nanoparticles relative to undoped nanoparticles, further confirming weak coupling between Fe and Tb spins at room temperature. The Gilbert damping constant, α, is remarkably low for the Tb-doped nanoparticles, with α = 0.024 ± 0.003. These nanoparticles, which have a large fixed moment, a large fluctuating moment and optically active rare-earth elements, are potential high-relaxivity T1 and T2 MRI agents with integrated optical signatures.

  12. Temperature-dependent structure of Tb-doped magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Rice, Katherine P.; Russek, Stephen E.; Geiss, Roy H.; Shaw, Justin M.; Usselman, Robert J.; Evarts, Eric R.; Silva, Thomas J.; Nembach, Hans T.; Arenholz, Elke; Idzerda, Yves U.

    2015-02-01

    High quality 5 nm cubic Tb-doped magnetite nanoparticles have been synthesized by a wet-chemical method to investigate tailoring of magnetic properties for imaging and biomedical applications. We show that the Tb is incorporated into the octahedral 3+ sites. High-angle annular dark-field microscopy shows that the dopant is well-distributed throughout the particle, and x-ray diffraction measurements show a small lattice parameter shift with the inclusion of a rare-earth dopant. Magnetization and x-ray magnetic circular dichroism data indicate that the Tb spins are unpolarized and weakly coupled to the iron spin lattice at room temperature, and begin to polarize and couple to the iron oxide lattice at temperatures below 50 K. Broadband ferromagnetic resonance measurements show no increase in magnetic damping at room temperature for Tb-doped nanoparticles relative to undoped nanoparticles, further confirming weak coupling between Fe and Tb spins at room temperature. The Gilbert damping constant, α, is remarkably low for the Tb-doped nanoparticles, with α = 0.024 ± 0.003. These nanoparticles, which have a large fixed moment, a large fluctuating moment and optically active rare-earth elements, are potential high-relaxivity T1 and T2 MRI agents with integrated optical signatures.

  13. Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

    PubMed

    Ong, Catherine W M; Elkington, Paul T; Brilha, Sara; Ugarte-Gil, Cesar; Tome-Esteban, Maite T; Tezera, Liku B; Pabisiak, Przemyslaw J; Moores, Rachel C; Sathyamoorthy, Tarangini; Patel, Vimal; Gilman, Robert H; Porter, Joanna C; Friedland, Jon S

    2015-05-01

    Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.

  14. A Multi-Antigenic Adenoviral-Vectored Vaccine Improves BCG-Induced Protection of Goats against Pulmonary Tuberculosis Infection and Prevents Disease Progression

    PubMed Central

    Pérez de Val, Bernat; Vidal, Enric; Villarreal-Ramos, Bernardo; Gilbert, Sarah C.; Andaluz, Anna; Moll, Xavier; Martín, Maite; Nofrarías, Miquel; McShane, Helen; Vordermeier, H. Martin; Domingo, Mariano

    2013-01-01

    The “One world, one health” initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine. Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes. The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions. Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG. PMID:24278420

  15. Lumbo-sacral spine disease due to bovine tuberculosis in a patient with concurrent pulmonary disease.

    PubMed

    Ahmad, Nawaid; Srinivasan, Koottalai; Panayi, Jeannette; Moudgil, Harmesh

    2011-12-01

    Lumbo-sacral spinal disease due to bovine tuberculosis (TB) in a patient with concurrent pulmonary disease is rare. We report this unpredicted finding in an immunocompetent patient and discuss the natural history in an area of low prevalence.

  16. Detection of pulmonary and extrapulmonary tuberculosis patients with the 38-kilodalton antigen from Mycobacterium tuberculosis in a rapid membrane-based assay.

    PubMed Central

    Zhou, A T; Ma, W L; Zhang, P Y; Cole, R A

    1996-01-01

    A rapid membrane-based serologic assay using the 38-kDa antigen from Mycobacterium tuberculosis for the diagnosis of tuberculosis (TB) was evaluated with 201 patients with pulmonary TB, 67 patients with extrapulmonary TB, 79 Mycobacterium bovis BCG-vaccinated healthy controls, and 77 non-TB respiratory patients. The overall sensitivities, specificities, and positive and negative predictive values were, respectively, 92, 92, 84, and 96% for sputum-positive TB patients; 70, 92, 87, and 79% for sputum-negative TB patients; and 76, 92, 80, and 90% for extrapulmonary-TB patients. Only 2% (1 of 44) of the healthy control BCG-vaccinated subjects gave weak positive signals in the assay, indicating that this rapid serological assay is a valuable aid in clinical diagnosis for both pulmonary and extrapulmonary TB. PMID:8705680

  17. WHO's End TB Strategy: From stopping to ending the global TB epidemic.

    PubMed

    Uplekar, Mukund; Raviglione, Mario

    2015-10-01

    The 67th World Health Assembly of 2014 adopted the "End TB Strategy" with a vision of making the world free of tuberculosis (TB) and with the goal of ending the global TB epidemic by the year 2035. World Health Organization's "End TB Strategy" captures this holistic response in its four principles and three pillars. The three high-level indicators of the "End TB Strategy" - reductions in TB deaths, reductions in the TB incidence rate and the percentage of TB patients and their households experiencing catastrophic costs - are relevant to all countries.

  18. Litigation as TB Rights Advocacy

    PubMed Central

    2016-01-01

    Abstract One thousand people die every day in India as a result of TB, a preventable and treatable disease, even though the Constitution of India, government schemes, and international law guarantee available, accessible, acceptable, quality health care. Failure to address the spread of TB and to provide quality treatment to all affected populations constitutes a public health and human rights emergency that demands action and accountability. As part of a broader strategy, health activists in India employ Public Interest Litigation (PIL) to hold the state accountable for rights violations and to demand new legislation, standards for patient care, accountability for under-spending, improvements in services at individual facilities, and access to government entitlements in marginalized communities. Taking inspiration from right to health PIL cases (PILs), lawyers in a New Delhi-based rights organization used desk research, fact-findings, and the Right To Information Act to build a TB PIL for the Delhi High Court, Sanjai Sharma v. NCT of Delhi and Others (2015). The case argues that inadequate implementation of government TB schemes violates the Constitutional rights to life, health, food, and equality. Although PILs face substantial challenges, this paper concludes that litigation can be a crucial advocacy and accountability tool for people living with TB and their allies. PMID:27781000

  19. Pulmonary toxicity of trichloroethylene: induction of changes in surfactant phospholipids and phospholipase A2 activity in the mouse lung.

    PubMed

    Scott, J E; Forkert, P G; Oulton, M; Rasmusson, M G; Temple, S; Fraser, M O; Whitefield, S

    1988-08-01

    Trichloroethylene (TCE) is a common organic solvent in use as a dry cleaning agent as well as an inhalant anesthetic. Nevertheless the effects of this material on the pulmonary surfactant which prevents alveolar collapse at maximal expiration is not known. Therefore, we have examined the effect of TCE on the intra- and extracellular surfactant pools and the activity of phospholipase A2, an enzyme which controls the remodeling of phosphatidylcholine to dipalmitoylphosphatidylcholine, the primary constituent of the pulmonary surfactant. Male CD-1 mice were treated ip with 2500 or 3000 mg/kg TCE. Twenty-four hours later mice were anesthetized and the lungs lavaged. Mice were then killed, the lungs perfused and excised, and subcellular fractions including lamellar bodies prepared. Some lungs were prepared for ultrastructural examination. Phospholipase A2 was assayed in all subcellular fractions. Phospholipid was assayed in the lavage (extracellular surfactant) and the lamellar bodies (intracellular surfactant). TCE (2500 mg/kg) caused selective exfoliation of Clara cells. However, only the dose of 3000 mg/kg TCE produced a significant decrease in the intracellular surfactant phospholipid. Minimal changes occurred in the phospholipid profiles. Phospholipase A2 specific activity was significantly decreased at both dosages within the lung microsomal fraction. In addition after treatment with 3000 mg/kg TCE the enzyme activity in the lamellar body fraction was significantly increased. These data suggest that inhalation of TCE may damage the enzymes which are responsible for synthesizing the pulmonary surfactant resulting in lower amounts of surfactant being stored and available for secretion into the alveolus.

  20. Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation.

    PubMed

    Wang, Guoliang; Ma, Ning; Meng, Liukun; Wei, Yingjie; Gui, Jingang

    2015-12-01

    Over-activated PI3K/Akt signaling, a pathway strongly related to cancer survival and proliferation, has been reported recently to be involved in pulmonary artery smooth muscle cell apoptosis and proliferation in pulmonary hypertension (PH). In this study, we observed greatly increased lipocalin-2 (Lcn2) expression accompanied with over-activated PI3K/Akt signaling in a standard rat model of PH induced by monocrotaline. In view of the close relationship between Lcn2 and PI3K/Akt pathway, we hypothesized that the up-regulated Lcn2 might be a trigger of over-activated PI3K/Akt signaling in PH. Our results showed that Lcn2 significantly activated the PI3K/Akt pathway (determined by augmented Akt phosphorylation and up-regulated Mdm2) and significantly promoted proliferation (assessed by Ki67 staining) in cultured human pulmonary artery smooth muscle cells. Furthermore, we demonstrated that inhibition of Akt phosphorylation (LY294002) abrogated the Lcn2-promoted proliferation in cultured human pulmonary artery smooth muscle cells. In conclusion, Lcn2 significantly promoted human pulmonary artery smooth muscle cell proliferation by activating PI3K/Akt pathway. Further study on the role and mechanism of Lcn2 will help explore novel therapeutic strategies based on attenuating over-activated PI3K/Akt signaling in PH.

  1. Bronchial asthma and chronic obstructive pulmonary disease: research activity in Arab countries

    PubMed Central

    2014-01-01

    Background Chronic respiratory diseases, like bronchial asthma and chronic obstructive pulmonary disease (COPD), are a worldwide health problem. Quantitative and qualitative assessment of asthma and COPD-related research from Arab countries has not been explored and there are few internationally published reports on such field. The main objectives of this study were to analyze research output originating from Arab countries in the field of bronchial asthma and COPD. Methods Original scientific articles or reviews published from the 22 Arab countries were screened using specific words pertaining to asthma and COPD using Scopus database and search engine. Research productivity was evaluated based on: (a) total and trends of contribution of each Arab country to asthma and COPD research and (b) journals in which researchers from Arab countries published their research. Results The total number of original research and review articles published globally about bronchial asthma and COPD was 163,964. The leading country in bronchial asthma and COPD research was United States of America (38,632; 23.56%). Worldwide, Turkey ranked 19th while Israel and Iran ranked 25th and 29th respectively. Among Arab countries, Egypt and Kingdom of Saudi Arabia came on positions 39th and 43rd, respectively. A total of 1,304 documents about bronchial asthma and COPD were published from Arab countries which represents 0.8% of the global research output. Research in bronchial asthma was almost double that in COPD. Research from Arab countries was low and showed a significant increase after 2000. Approximately 12% of research activity in asthma and COPD from Arab countries was published in Saudi Medical Journal, Annals of Saudi Medicine, Eastern Mediterranean Health Journal and Tunisie Medicale. Kingdom of Saudi Arabia, with a total publication of 353 (27.07%) ranked first among the Arab countries while University of Kuwait was the most productive institution with a total of 123 (9

  2. Control measures to trace ≤ 15-year-old contacts of index cases of active pulmonary tuberculosis

    PubMed Central

    Oliveira, Cláudia Di Lorenzo; de Melo, Angelita Cristine; de Oliveira, Lílian Ruth Silva; Froede, Emerson Lopes; Camargos, Paulo

    2015-01-01

    This was descriptive study carried out in a medium-sized Brazilian city. In ≤ 15-year-old contacts of index cases of active pulmonary tuberculosis, we assessed compliance with the Brazilian national guidelines for tuberculosis control. We interviewed 43 contacts and their legal guardians. Approximately 80% of the contacts were not assessed by the municipal public health care system, and only 21% underwent tuberculin skin testing. The results obtained with the Chi-square Automatic Interaction Detector method suggest that health care teams have a biased attitude toward assessing such contacts and underscore the need for training health professionals regarding tuberculosis control programs. PMID:26578137

  3. Concurrent administration of heparin and activated protein C in a patient with pulmonary embolism and severe sepsis with positive outcome.

    PubMed

    Juneja, Deven; Mohan, S; Veturi, Vivek V; Gopal, Palepu B

    2009-01-01

    Results of the PROWESS trial suggested that heparin may reduce the efficacy of recombinant human activated protein C (rhAPC) and the XPRESS study also showed increased bleeding complications in patients receiving heparin with rhAPC. Although it has been shown that heparin prophylaxis may be used along with rhAPC, no study has shown the interaction between continuous heparin infusion and rhAPC. Here, we report a case of severe sepsis with pulmonary embolism who was concurrently administered heparin and rhAPC infusions, with positive results and no bleeding complications.

  4. TB or not TB? Difficulties in the diagnosis of tuberculosis in HIV-negative immigrants to Germany

    PubMed Central

    2011-01-01

    Background Immigrants to Germany and their children are at particular risk for tuberculosis (TB). Methods 35 Patients (10 male/25 female aged 2 - 59 years (median 33 years) originating mostly from high incidence countries in Asia (19 [54.3%]) in Africa (14 [40.0%] and East Europe (2 [5.7%]), attended at the Tropical Medicine unit were analysed. Results Primary clinical presentation was most frequently lymphadenitis (13 [37.1%]). other organs involved included bones (7 [20.0%]), central nervous system (5 [14.3%]), urogenital organs (3 [8.6%]), lung (3 [8.6%]), mediastinum, (2 [5.7%]) and abdomen (2 [5.7%]). ESR was abnormal in 21/28 (75.0%), CRP in 20/35 (57.1%), and protein electrophoresis in 22/26 (84.6%) cases. The tuberculin skin test was strongly positive in all 15 cases where the test had been performed. Tuberculosis interferon gamma release assay (TB-IGRA) was positive in all 35 cases (100%). PCR for nucleic acids of Mycobacterium (M.) tuberculosis complex was positive in only 7/20 (35.0%) cases. M. tuberculosis was identified in 32/35 (91.4%), M. bovis in 2 (5.7%) cases. 1 case was diagnosed clinically. All patients were negative for HIV. Typical histopathology was seen in the 29 cases, where biopsies had been taken. Chest-X-ray did not reveal specific pulmonary lesions in the majority of cases (22/35 [62.9%]). Diagnosis of TB was mostly delayed (4 to 299 weeks, [median 8]). The most frequent primary suspicion was a malignancy (17/35 [48.6%]) while TB was initially suspected in 5 cases only. Diagnosis of TB is impeded by its multifaceted presentation especially in immigrants. PMID:22024436

  5. Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies.

    PubMed

    Kramnik, Igor; Beamer, Gillian

    2016-03-01

    A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co-evolution shaped M . tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data. In mice, there is clear genetic basis for susceptibility. Although the spectra of human and mouse TB do not completely overlap, comparison of human TB with mouse lesions across genetically diverse strains firmly establishes points of convergence. By embracing the genetic heterogeneity of the mouse population, we gain tremendous advantage in the quest for suitable in vivo models. Below, we review genetically defined mouse models that recapitulate a key element of M.tb pathogenesis-induction of necrotic TB lesions in the lungs-and discuss how these models may reflect TB stratification and pathogenesis in humans. The approach ensures that roles that mouse models play in basic and translational TB research will continue to increase allowing researchers to address fundamental questions of TB pathogenesis and bacterial physiology in vivo using this well-defined, reproducible, and cost-efficient system. Combination of the new generation mouse models with advanced imaging technologies will also allow rapid and inexpensive assessment of experimental vaccines and therapies prior to testing in larger animals and clinical trials.

  6. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

    PubMed

    Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

    2010-11-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs.

  7. TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites

    PubMed Central

    Ammerman, Michelle L.; Presnyak, Vladimir; Fisk, John C.; Foda, Bardees M.; Read, Laurie K.

    2010-01-01

    TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5′ ends of pan-edited RNAs than at their 3′ ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3′ to 5′ progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3′ ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA–RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3′ to 5′ progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

  8. Inhibition of secretory phospholipase A2 activity attenuates acute cardiogenic pulmonary edema induced by isoproterenol infusion in mice after myocardial infarction.

    PubMed

    Kawabata, Kenichi; Fujioka, Daisuke; Kobayashi, Tsuyoshi; Saito, Yukio; Obata, Jun-Ei; Nakamura, Takamitsu; Yano, Toshiaki; Watanabe, Kazuhiro; Watanabe, Yosuke; Mishina, Hideto; Kugiyama, Kiyotaka

    2010-10-01

    Several types of secretory phospholipase A2 (sPLA2) are expressed in lung tissue, yielding various eicosanoids that might cause pulmonary edema. This study examined whether inhibition of sPLA2 activity attenuates acute cardiogenic pulmonary edema in mice. Acute cardiogenic pulmonary edema was induced in C57BL/6J male mice by an increase in heart rate with continuous intravenous infusion of isoproterenol (ISP) (10 mg/kg/h) at 2 weeks after the creation of myocardial infarction by left coronary artery ligation. Just before ISP infusion, a single intraperitoneal injection of 100 mg/kg LY374388, a prodrug of LY329722 that inhibits sPLA2 activity, or vehicle was administered. The ISP infusion after myocardial infarction induced interstitial and alveolar edema on lung histology. Furthermore, it increased the lung-to-body weight ratio, pulmonary vascular permeability evaluated by the Evans blue extravasation method, lung activity of sPLA2, and lung content of thromboxane A2 and leukotriene B4. These changes were significantly attenuated by LY374388 treatment. In Kaplan-Meier analysis, the survival rate during the ISP infusion after myocardial infarction was significantly higher in LY374388- than in vehicle-treated mice. Similar results were obtained with another inhibitor of sPLA2 activity, para-bromophenacyl bromide. In conclusion, inhibition of sPLA2 activity suppressed acute cardiogenic pulmonary edema.

  9. Selective activation of angiotensin AT2 receptors attenuates progression of pulmonary hypertension and inhibits cardiopulmonary fibrosis

    PubMed Central

    Bruce, E; Shenoy, V; Rathinasabapathy, A; Espejo, A; Horowitz, A; Oswalt, A; Francis, J; Nair, A; Unger, T; Raizada, M K; Steckelings, U M; Sumners, C; Katovich, M J

    2015-01-01

    Background and Purpose Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right-heart failure and death. A dys-regulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin AT2 receptor in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH. Experimental Approach A single s.c. injection of MCT (50 mg·kg−1) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2 weeks of MCT administration, a subset of animals began receiving either 0.03 mg·kg−1 C21, 3 mg·kg−1 PD-123319 or 0.5 mg·kg−1 A779 for an additional 2 weeks, after which right ventricular haemodynamic parameters were measured and tissues were collected for gene expression and histological analyses. Key Results Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular fibrosis. These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro-inflammatory cytokines and favourable modulation of the lung RAS. Conversely, co-administration of the AT2 receptor antagonist, PD-123319, or the Mas antagonist, A779, abolished the protective actions of C21. Conclusions and Implications Taken together, our results suggest that the AT2 receptor agonist, C21, may hold promise for patients with PH. PMID:25522140

  10. TB vaccines in clinical development.

    PubMed

    Ginsberg, Ann M; Ruhwald, Morten; Mearns, Helen; McShane, Helen

    2016-08-01

    The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on TB Vaccines in Clinical Development, and Clinical Research: Data and Findings. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30].

  11. Pulmonary Hypertension and Pulmonary Vasodilators.

    PubMed

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities.

  12. Pulmonary Edema

    MedlinePlus

    ... suddenly or develop over time. Sudden (acute) pulmonary edema symptoms Extreme shortness of breath or difficulty breathing ( ... fatal if not treated. Long-term (chronic) pulmonary edema symptoms Having more shortness of breath than normal ...

  13. Pulmonary Rehabilitation

    MedlinePlus

    Pulmonary Rehabilitation If you have shortness of breath because of lung problems, you may have asked yourself: • Can I ... medications do I really need to take? Pulmonary rehabilitation can help answer these and other questions. Enrolling ...

  14. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  15. Pulmonary Embolism

    MedlinePlus

    ... pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  16. Declining tuberculosis notification trend associated with strengthened TB and expanded HIV care in Swaziland.

    PubMed

    Haumba, S; Dlamini, T; Calnan, M; Ghazaryan, V; Smith-Arthur, A E; Preko, P; Ehrenkranz, P

    2015-06-21

    This retrospective observational review documents the efforts of the Swaziland National Tuberculosis (TB) Control Programme between 2004 and 2014. The objective is to describe the disparity between actual declines in case notification and increases in estimated incidence. The review of policies and practices shows the most influential factors associated with the decrease in TB case notification to be an increase in access to antiretroviral therapy for co-infected TB patients, the general success of TB and human immunodeficiency virus service integration in the country and improvements in implementation of all components of directly observed treatment, active case finding, and rapid diagnosis using new technologies.

  17. Optimal Control for TB disease with vaccination assuming endogeneous reactivation and exogeneous reinfection

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.

    2016-06-01

    Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.

  18. Pulmonary Chlamydia muridarum challenge activates lung interstitial macrophages which correlate with IFN-γ production and infection control in mice.

    PubMed

    Gracey, Eric; Baglaenko, Yuriy; Prayitno, Nadia; Van Rooijen, Nico; Akram, Ali; Lin, Aifeng; Chiu, Basil; Inman, Robert D

    2015-12-01

    Protective immunity to the pathogen Chlamydia is dependent on a robust IFN-γ response generated by innate and adaptive lymphocytes. Here we assess the role of the macrophage in orchestrating a protective response in vivo to the murine pathogen, Chlamydia muridarum. During acute pulmonary and peritoneal infection, resident macrophages in both sites are infected with C. muridarum and adopt an inflammatory phenotype. In the lung, this activation is restricted to interstitial macrophages, which harbor higher levels of C. muridarum 16sRNA than alveolar macrophages. We examined innate and adaptive lymphocyte activation in the peritoneal cavity with macrophage depletion and with adoptive transfer of infected macrophages. These experiments demonstrate macrophage activation correlates with a protective IFN-γ response and effective control of C. muridarum. These studies suggest that a quantitative or qualitative alteration in macrophages may play a key role in the development of Chlamydia-associated diseases.

  19. HIV-Associated TB: Facts 2013

    MedlinePlus

    ... HIV worldwide are infected with latent TB. Persons co-infected with TB and HIV are 29.6 ... 5 million in 2011).  Antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) should be given to ...

  20. Detection of Pulmonary Nodules in CT Images Based on Fuzzy Integrated Active Contour Model and Hybrid Parametric Mixture Model

    PubMed Central

    Li, Bin; Chen, Kan; Tian, Lianfang; Yeboah, Yao; Ou, Shanxing

    2013-01-01

    The segmentation and detection of various types of nodules in a Computer-aided detection (CAD) system present various challenges, especially when (1) the nodule is connected to a vessel and they have very similar intensities; (2) the nodule with ground-glass opacity (GGO) characteristic possesses typical weak edges and intensity inhomogeneity, and hence it is difficult to define the boundaries. Traditional segmentation methods may cause problems of boundary leakage and “weak” local minima. This paper deals with the above mentioned problems. An improved detection method which combines a fuzzy integrated active contour model (FIACM)-based segmentation method, a segmentation refinement method based on Parametric Mixture Model (PMM) of juxta-vascular nodules, and a knowledge-based C-SVM (Cost-sensitive Support Vector Machines) classifier, is proposed for detecting various types of pulmonary nodules in computerized tomography (CT) images. Our approach has several novel aspects: (1) In the proposed FIACM model, edge and local region information is incorporated. The fuzzy energy is used as the motivation power for the evolution of the active contour. (2) A hybrid PMM Model of juxta-vascular nodules combining appearance and geometric information is constructed for segmentation refinement of juxta-vascular nodules. Experimental results of detection for pulmonary nodules show desirable performances of the proposed method. PMID:23690876

  1. Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice.

    PubMed

    Lay, Margarita K; Céspedes, Pablo F; Palavecino, Christian E; León, Miguel A; Díaz, Rodrigo A; Salazar, Francisco J; Méndez, Gonzalo P; Bueno, Susan M; Kalergis, Alexis M

    2015-06-01

    Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.

  2. Detection of pulmonary nodules in CT images based on fuzzy integrated active contour model and hybrid parametric mixture model.

    PubMed

    Li, Bin; Chen, Kan; Tian, Lianfang; Yeboah, Yao; Ou, Shanxing

    2013-01-01

    The segmentation and detection of various types of nodules in a Computer-aided detection (CAD) system present various challenges, especially when (1) the nodule is connected to a vessel and they have very similar intensities; (2) the nodule with ground-glass opacity (GGO) characteristic possesses typical weak edges and intensity inhomogeneity, and hence it is difficult to define the boundaries. Traditional segmentation methods may cause problems of boundary leakage and "weak" local minima. This paper deals with the above mentioned problems. An improved detection method which combines a fuzzy integrated active contour model (FIACM)-based segmentation method, a segmentation refinement method based on Parametric Mixture Model (PMM) of juxta-vascular nodules, and a knowledge-based C-SVM (Cost-sensitive Support Vector Machines) classifier, is proposed for detecting various types of pulmonary nodules in computerized tomography (CT) images. Our approach has several novel aspects: (1) In the proposed FIACM model, edge and local region information is incorporated. The fuzzy energy is used as the motivation power for the evolution of the active contour. (2) A hybrid PMM Model of juxta-vascular nodules combining appearance and geometric information is constructed for segmentation refinement of juxta-vascular nodules. Experimental results of detection for pulmonary nodules show desirable performances of the proposed method.

  3. Effects of simulated pulmonary surfactant on the cytotoxicity and DNA-damaging activity of respirable quartz and kaolin.

    PubMed

    Gao, N; Keane, M J; Ong, T; Wallace, W E

    2000-06-09

    Respirable-sized quartz and kaolin dusts were pretreated with simulated pulmonary surfactant dispersions of dipalmitoyl phosphatidylcholine (DPPC) in saline to model the conditioning of particles depositing in alveolar regions of the lung. DPPC-treated and untreated dusts were used to challenge lavaged rat pulmonary alveolar macrophages in vitro. Cytotoxicity was determined over a 5-d period using both total and viable cell counts from a fluorescence-based viability assay. DNA damage, as an indication of genotoxicity, was determined over a 7-d period by the single-cell gel electrophoresis assay. Untreated quartz and kaolin both expressed a significant and potent cytotoxicity, which increased with concentration and time. DPPC-surfactant pretreatment delayed significant expression of this cytotoxicity until 3 to 5 d after challenge. Untreated quartz also caused DNA damage, which increased with concentration and time. DPPC-surfactant treatment of quartz delayed most DNA damage expression to 5 and 7 d. Untreated kaolin expressed weaker activity for DNA damage, significant at the highest concentration through 5 d, and at the higher concentrations on d 7. Surfactant treatment delayed most kaolin activity for DNA damage to 7 d after challenge.

  4. Pulmonary Hypertension

    MedlinePlus

    ... on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or PH, is increased pressure in the pulmonary arteries. These arteries carry blood from your heart to your lungs to pick up oxygen. PH causes symptoms such as shortness of ...

  5. Is TB in Your Curriculum?

    ERIC Educational Resources Information Center

    Kerr, Joanne; Elwell, Jack

    2002-01-01

    Points out the importance of effective health education to fight against tuberculosis (TB) which is the number one fatal infectious disease around the world. Describes a science curriculum on tuberculosis that includes information on the facts about tuberculosis, a forum on tuberculosis, and evaluation. (Contains 17 references.) (YDS)

  6. Cross section measurement of the 159Tb(n, γ)Tb160 nuclear reaction

    NASA Astrophysics Data System (ADS)

    Dzysiuk, N.; Kadenko, I.; Gressier, V.; Koning, A. J.

    2015-04-01

    The cross section of the 159Tb(n, γ)Tb160 reaction was measured in four mono-energetic neutron fields of energy 3.7, 4.3, 5.4, and 6.85 MeV, respectively, with the activation technique applied to metal discs of natural composition. To ensure an acceptable precision of the results all major sources of uncertainties were taken into account. Calculations of detector efficiency, incident neutron spectrum and correction factors were performed with the Monte Carlo code (MCNPX), whereas theoretical excitation functions were calculated with the TALYS-1.2 code and compared to the experimental cross section values. This paper presents both measurements and calculation leading to the cross section values.

  7. Pulmonary tuberculosis in severely-malnourished or HIV-infected children with pneumonia: a review.

    PubMed

    Chisti, Mohammod Jobayer; Ahmed, Tahmeed; Pietroni, Mark A C; Faruque, Abu S G; Ashraf, Hasan; Bardhan, Pradip K; Hossain, Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus

    2013-09-01

    Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/ very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies

  8. MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis

    PubMed Central

    Azman, Andrew S.; Cobelens, Frank G.; Dowdy, David W.

    2017-01-01

    Background In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality. Methods We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology. Results Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4–52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6–55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20–74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025. Conclusions Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected

  9. Pulmonary tuberculosis among migrants in Shandong, China: factors associated with treatment delay

    PubMed Central

    Zhou, Chengchao; Chu, Jie; Geng, Hong; Wang, Xingzhou; Xu, Lingzhong

    2014-01-01

    Objective A timely initiation of treatment is crucial to better control tuberculosis (TB). The aim of this study is to describe treatment delay among migrant patients with TB and to identify factors associated with treatment delay, so as to provide evidence for strategy development and improvement of TB control among migrants in China. Design A cross-sectional study was conducted in Shandong province of China. A total of 314 confirmed smear positive migrant patients with pulmonary TB were included. Univariate logistic regression was used to analyse the association of variables with treatment delay among migrant patients with TB. A multilogistic regression model was developed to further assess the effect of variables on treatment delay. Results Of 314 migrant patients with TB, 65.6% experienced treatment delay (>1 day). Household income level, diagnosis symptom severity, understanding of whether TB is curable or not and knowledge about the free TB treatment policy are factors significantly associated with treatment delay. Conclusions Economic status and knowledge about TB are key barriers to accessing TB treatment. An integrated policy of carrying out TB-related health education and publicising the free TB treatment policy among migrants is needed. Health insurance schemes for migrants should be modified to make them transferrable and pro-poor. PMID:25534210

  10. Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life

    PubMed Central

    Furlanetto, Karina C.; Pinto, Isabela F. S.; Sant’Anna, Thais; Hernandes, Nidia A.; Pitta, Fabio

    2016-01-01

    ABSTRACT Objective To compare the profiles of patients with chronic obstructive pulmonary disease (COPD) considered physically active or inactive according to different classifications of the level of physical activity in daily life (PADL). Method Pulmonary function, dyspnea, functional status, body composition, exercise capacity, respiratory and peripheral muscle strength, and presence of comorbidities were assessed in 104 patients with COPD. The level of PADL was quantified with a SenseWear Armband activity monitor. Three classifications were used to classify the patients as physically active or inactive: 30 minutes of activity/day with intensity >3.2 METs, if age ≥65 years, and >4 METs, if age <65 years; 30 minutes of activity/day with intensity >3.0 METs, regardless of patient age; and 80 minutes of activity/day with intensity >3.0 METs, regardless of patient age. Results In all classifications, when compared with the inactive group, the physically active group had better values of anthropometric variables (higher fat-free mass, lower body weight, body mass index and fat percentage), exercise capacity (6-minute walking distance), lung function (forced vital capacity) and functional status (personal care domain of the London Chest Activity of Daily Living). Furthermore, patients classified as physically active in two classifications also had better peripheral and expiratory muscle strength, airflow obstruction, functional status, and quality of life, as well as lower prevalence of heart disease and mortality risk. Conclusion In all classification methods, physically active patients with COPD have better exercise capacity, lung function, body composition, and functional status compared to physically inactive patients. PMID:27683835

  11. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    EPA Pesticide Factsheets

    pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets.This dataset is associated with the following publication:Gordon , C., P. Phillips , A. Johnstone , T. Beasley , A. Ledbetter , M. Schladweiler , S. Snow, and U. Kodavanti. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, USA, 28(5): 203-15, (2016).

  12. The Xanthine Derivative KMUP-1 Attenuates Serotonin-Induced Vasoconstriction and K+-Channel Inhibitory Activity via the PKC Pathway in Pulmonary Arteries

    PubMed Central

    Dai, Zen-Kong; Liu, Yu-Wei; Hsu, Jong-Hau; Yeh, Jwu-Lai; Chen, Ing-Jun; Wu, Jiunn-Ren; Wu, Bin-Nan

    2015-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a potent pulmonary vasoconstrictor that promotes pulmonary artery smooth muscle cell (PASMC) proliferation. 5-HT-induced K+ channel inhibition increases [Ca2+]i in PASMCs, which is a major trigger for pulmonary vasoconstriction and development of pulmonary arterial hypertension (PAH). This study investigated whether KMUP-1 reduces pulmonary vasoconstriction in isolated pulmonary arteries (PAs) and attenuates 5-HT-inhibited K+ channel activities in PASMCs. In endothelium-denuded PA rings, KMUP-1 (1 μM) dose-dependently reduced 5-HT (100 μM) mediated contractile responses. Responses to KMUP-1 were reversed by K+ channel inhibitors (TEA, 10 mM, 4-aminopyridine, 5 mM, and paxilline, 10 μM). In primary PASMCs, KMUP-1 also dose-dependently restored 5-HT-inhibited voltage-gated K+-channel (Kv1.5 and Kv2.1) and large-conductance Ca2+-activated K+-channel (BKCa) proteins, as confirmed by immunofluorescent staining. Furthermore, 5-HT (10 μM)-inhibited Kv1.5 protein was unaffected by the PKA inhibitor KT5720 (1 μM) and the PKC activator PMA (1 μM), but these effects were reversed by KMUP-1 (1 μM), 8-Br-cAMP (100 μM), chelerythrine (1 μM), and KMUP-1 combined with a PKA/PKC activator or inhibitor. Notably, KMUP-1 reversed 5-HT-inhibited Kv1.5 protein and this response was significantly attenuated by co-incubation with the PKC activator PMA, suggesting that 5-HT-mediated PKC signaling can be modulated by KMUP-1. In conclusion, KMUP-1 ameliorates 5-HT-induced vasoconstriction and K+-channel inhibition through the PKC pathway, which could be valuable to prevent the development of PAH. PMID:25999786

  13. Thermal and optical properties of Tb(III), Eu(III) and Tb(III)/Eu(III) co-complexed silicone fluorinated acrylate copolymer

    NASA Astrophysics Data System (ADS)

    Zhai, Yinfeng; Xie, Hongde; Cai, Haijun; Cai, Peiqing; Seo, Hyo Jin

    2015-07-01

    Tb(III), Eu(III) and Tb(III)/Eu(III) activated silicone fluorinated acrylate (SFA) have been successfully synthesized using the method of semi-continuous emulsion polymerization. The copolymers are characterized by flourier transform infrared (FT-IR), thermal gravity analysis (TGA), photoluminescence excitation (PLE) and emission (PL) spectroscopy. The copolymer containing Tb(III) and Eu(III) ions display green and red luminescent colors under UV light excitation, respectively. The TGA curves show the thermal decomposition temperatures of the copolymers are up to about 300 °C. The PL spectra show a strong green emission at 546 nm (5D4 → 7F5) of Tb(III) complexed copolymers, and show a prominent red emission at 615 nm (5D0 → 7F2) of Eu(III) complexed copolymers. Different concentrations of Eu(III) and Tb(III) ions are introduced into the copolymer and the energy transfer from Tb(III) to Eu(III) ions in the copolymer was found. Thus, based on the results it can be suggested that SFA:Eu(III), SFA:Tb(III) and SFA:Tb(III)/Eu(III) can be used potentially as luminescent materials.

  14. Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

    PubMed Central

    Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

    2014-01-01

    Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

  15. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis.

    PubMed

    Bell, Lucy C K; Pollara, Gabriele; Pascoe, Mellissa; Tomlinson, Gillian S; Lehloenya, Rannakoe J; Roe, Jennifer; Meldau, Richard; Miller, Robert F; Ramsay, Alan; Chain, Benjamin M; Dheda, Keertan; Noursadeghi, Mahdad

    2016-03-01

    Increased risk of tuberculosis (TB) associated with HIV-1 infection is primarily attributed to deficient T helper (Th)1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART) exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis. We sought to define these effects in patients with active TB by transcriptional profiling of tuberculin skin tests (TST) to make comprehensive molecular level assessments of in vivo human immune responses at the site of a standardised mycobacterial challenge. We showed that the TST transcriptome accurately reflects the molecular pathology at the site of human pulmonary TB, and used this approach to investigate immune dysregulation in HIV-1/TB co-infected patients with distinct clinical phenotypes associated with TST reactivity or anergy and unmasking TB immune reconstitution inflammatory syndrome (IRIS) after initiation of ART. HIV-1 infected patients with positive TSTs exhibited preserved Th1 responses but deficient immunoregulatory IL10-inducible responses. Those with clinically negative TSTs revealed profound anergy of innate as well as adaptive immune responses, except for preservation of type 1 interferon activity, implicated in impaired anti-mycobacterial immunity. Patients with unmasking TB IRIS showed recovery of Th1 immunity to normal levels, but exaggerated Th2-associated responses specifically. These mechanisms of immune dysregulation were localised to the tissue microenvironment and not evident in peripheral blood. TST

  16. Gallium-67 imaging in pulmonary eosinophilic granuloma

    SciTech Connect

    Makhija, M.C.; Davis, G.

    1984-03-01

    Gallium-67 citrate has been known to localize in the lungs in a variety of pulmonary diseases. Abnormal lung activity implies active underlying disease. Serial Ga-67 lung scans may be helpful when steroids are used as therapeutic agents. A case of pulmonary eosinophic granuloma is reported here with diffuse bilateral Ga-67 pulmonary activity.

  17. An active one-lobe pulmonary simulator with compliance control for medical training in neonatal mechanical ventilation.

    PubMed

    Baldoli, Ilaria; Tognarelli, Selene; Cecchi, Francesca; Scaramuzzo, Rosa Teresa; Ciantelli, Massimiliano; Gentile, Marzia; Cuttano, Armando; Laschi, Cecilia; Menciassi, Arianna; Boldrini, Antonio; Dario, Paolo

    2014-06-01

    Mechanical ventilation is a current support therapy for newborns affected by respiratory diseases. However, several side effects have been observed after treatment, making it mandatory for physicians to determine more suitable approaches. High fidelity simulation is an efficient educational technique that recreates clinical experience. The aim of the present study is the design of an innovative and versatile neonatal respiratory simulator which could be useful in training courses for physicians and nurses as for mechanical ventilation. A single chamber prototype, reproducing a pulmonary lobe both in size and function, was designed and assembled. Volume and pressure within the chamber can be tuned by the operator through the device control system, in order to simulate both spontaneous and assisted breathing. An innovative software-based simulator for training neonatologists and nurses within the continuing medical education program on respiratory disease management was validated. Following the clinical needs, three friendly graphic user interfaces were implemented for simulating three different clinical scenarios (spontaneous breathing, controlled breathing and triggered/assisted ventilation modalities) thus providing physicians with an active experience. The proposed pulmonary simulator has the potential to be included in the range of computer-driven technologies used in medical training, adding novel functions and improving simulation results.

  18. Sensory irritation and pulmonary irritation of cumene and n-propanol: mechanisms of receptor activation and desensitization.

    PubMed

    Kristiansen, U; Hansen, L; Nielsen, G D; Holst, E

    1986-07-01

    Cumene and n-propanol, model substances for alcohols and alkylbenzenes, were investigated for sensory irritation in mice. The concentrations within the first 2 min. depressing the respiratory rate by 50% due to the effect in the upper respiratory tract were 2,058 p.p.m. and 22,080 p.p.m., respectively. Activation of the sensory irritant receptor followed the dynamics of reversible bimolecular reactions. The extrapolated maximum response and the apparent dissociation constant were 114.3% and 2,723 p.p.m. for cumene and 68.4% and 8,178 p.p.m. for propanol, respectively. Later on desensitization was observed. The effect was weak for cumene but conspicuous for propanol. For cumene desensitization had the origin in the rise of a threshold. No change in the dissociation constant or the maximum response was found. For propanol a decrease in the maximum response, which may be explained by an allosteric effect, was observed. The pulmonary irritation response was weak for cumene but was for propanol more important than sensory irritation at high concentrations. The following hypotheses are put forward: the effect of pulmonary irritation on the tidal volume is mediated via the stretch receptors while the effect on the respiratory frequency is mediated via the J-receptors.

  19. A model dynamic for effect latent population to co-epidemic of HIV-TB

    NASA Astrophysics Data System (ADS)

    Jafaruddin, Sutimin, Ariyanto

    2014-02-01

    Threat of co-epidemic HIV-TB is a major problem that must be faced by countries around the world. In 2011, approximately about one-third of the 34 million people living with HIV worldwide is infected with latent TB. Persons co-infected with TB and HIV are 21-34 times more likely to develop active TB disease than persons without HIV. In this paper, we develop a simple co-epidemic model of HIV-TB. We calculate the basic reproduction ratio at the disease-free equilibrium, and the quasi-disease-free equilibrium, which we define as the existence of one disease along with the complete eradication of the other disease, and the co-infection equilibrium for specific conditions. Using this model, we study co-epidemic HIV-TB in Indonesia based on demography data in 2009 to explore the effects of hypothetical prevention and treatment scenarios. Our simple model of co-epidemic HIV-TB describes the importance of including the effects of HIV on TB and vice versa on the transmission and progression of the HIV and TB epidemic.

  20. Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease--changes in ATPase and acetylcholinesterase activity.

    PubMed

    Bukowska, Bożena; Sicińska, Paulina; Pająk, Aneta; Koceva-Chyla, Aneta; Pietras, Tadeusz; Pszczółkowska, Anna; Górski, Paweł; Koter-Michalak, Maria

    2015-12-01

    The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease.

  1. The Role of Apoptosis Associated Markers in Pathogenesis of Pulmonary Tuberculosis

    ClinicalTrials.gov

    2012-08-28

    To Compare the Serum Apoptosis-associated Markers Between Patients With Active TB and Patients With LTBI; To Evaluate the Efficiency of Apoptosis-associated Markers to Differentiate Potential of Active TB From LTBI

  2. Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection

    PubMed Central

    Wong, Emily B.; Akilimali, Ngomu Akeem; Govender, Pamla; Sullivan, Zuri A.; Cosgrove, Cormac; Pillay, Mona; Lewinsohn, David M.; Bishai, William R.; Walker, Bruce D.; Ndung'u, Thumbi; Klenerman, Paul; Kasprowicz, Victoria O.

    2013-01-01

    Background High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting. Methods A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 13), latent MTB infection (LTBI) only (n = 14), pulmonary tuberculosis (TB) only (n = 9), HIV only (n = 16), HIV and LTBI co-infection (n = 13) and HIV and TB co-infection (n = 15). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients. Results CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection. Conclusions The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB

  3. Symptom screening rules to identify active pulmonary tuberculosis: Findings from the Zambian South African Tuberculosis and HIV/AIDS Reduction (ZAMSTAR) trial prevalence surveys

    PubMed Central

    Claassens, M. M.; Floyd, S.; Ayles, H.; Beyers, N.

    2017-01-01

    Background High tuberculosis (TB) burden countries should consider systematic screening among adults in the general population. We identified symptom screening rules to be used in addition to cough ≥2 weeks, in a context where X-ray screening is not feasible, aiming to increase the sensitivity of screening while achieving a specificity of ≥85%. Methods We used 2010 Zambia South Africa Tuberculosis and HIV/AIDS Reduction (ZAMSTAR) survey data: a South African (SA) training dataset, a SA testing dataset for internal validation and a Zambian dataset for external validation. Regression analyses investigated relationships between symptoms or combinations of symptoms and active disease. Sensitivity and specificity were calculated for candidate rules. Results Among all participants, the sensitivity of using only cough ≥2 weeks as a screening rule was less than 25% in both SA and Zambia. The addition of any three of six TB symptoms (cough <2 weeks, night sweats, weight loss, fever, chest pain, shortness of breath), or 2 or more of cough <2 weeks, night sweats, and weight loss, increased the sensitivity to ~38%, while reducing specificity from ~95% to ~85% in SA and ~97% to ~92% in Zambia. Among HIV-negative adults, findings were similar in SA, whereas in Zambia the increase in sensitivity was relatively small (15% to 22%). Conclusion High TB burden countries should investigate cost-effective strategies for systematic screening: one such strategy could be to use our rule in addition to cough ≥2 weeks. PMID:28257424

  4. Microscopic observation drug susceptibility assay for the diagnosis of TB and MDR-TB in HIV-infected patients: a systematic review and meta-analysis.

    PubMed

    Wikman-Jorgensen, Philip; Llenas-García, Jara; Hobbins, Michael; Ehmer, Jochen; Abellana, Rosa; Gonçalves, Alessandra Queiroga; Pérez-Porcuna, Tomàs Maria; Ascaso, Carlos

    2014-10-01

    The objective of the present study was to assess the diagnostic accuracy of the microscopic observation drug susceptibility (MODS) assay for tuberculosis (TB) diagnosis in HIV-infected patients. MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, African Index Medicus, ResearchGate, SciELO, and the abstracts of the main conferences on infectious diseases and tropical medicine were searched, and other sources investigated. Only studies including HIV-infected patients evaluating MODS for the diagnosis of TB and using culture-based diagnostic tests as a gold standard were analysed. Summary sensitivity and specificity were calculated with a bivariate model. 3259 citations were found, 29 were selected for full-text review and 10 studies including 3075 samples were finally analysed. Overall diagnostic accuracy of MODS for the diagnosis of TB was a sensitivity of 88.3% (95% CI 86.18-90.2%) and specificity 98.2% (95% CI 97.75-98.55%). For multidrug-resistant (MDR)-TB, sensitivity was 89% (95% CI 66.07-97%) and specificity was 100% (95 CI 94.81-100%). For smear-negative pulmonary TB, a sensitivity of 88.2% (95% CI 86.1-89.9%) and specificity of 98.2% (95% CI 96.8-98.9%) were found. Costs varied between USD 0.72 and 7.31 per sample. Mean time to positivity was 8.24 days. MODS was found to have a good accuracy for the diagnosis of TB and MDR-TB in HIV-infected patients with low cost and fast results.

  5. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin.

    PubMed

    Foster, Derek M; Martin, Luke G; Papich, Mark G

    2016-01-01

    Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900

  6. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

    PubMed Central

    Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

    2016-01-01

    Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900

  7. Drug-resistant pulmonary tuberculosis in the Baja California-San Diego County border population.

    PubMed Central

    Peter, C R; Schultz, E; Moser, K; Cox, M; Freeman, R; Ramirez-Zetina, M; Lomeli, M R

    1998-01-01

    A study was conducted to determine the frequency of, and risk factors for, drug-resistant pulmonary tuberculosis (TB) among Baja California (BC) and San Diego County (SDC) residents. Another purpose was to document the amount of contact between pulmonary TB patients and residents of the opposite side of the the border. During the period from February 1995 to May 1996, pulmonary TB patients from BC (n = 427) and SDC (n = 331) were evaluated with cultures, drug susceptibility tests, and questionnaires. Drug resistance was found in 41% of the BC Mycobacterium tuberculosis complex (MTB) isolates and 20% of the SDC isolates. Resistance to both isoniazid (INH) and rifampin (RIF) varied from 1% of isolates from SDC patients to 17% of isolates from BC patients. Patients with a history of previous treatment had increased odds of drug-resistant disease. Older BC patients were more likely to have INH- or RIF-resistant TB. Although 42% of Tijuana TB patients reported recent contact with residents from SDC, travel to Mexico and contact with residents from Mexico were not significant risk factors for drug-resistant TB among SDC residents. However, the demonstrated contact between TB patients and residents on opposite sides of the border indicates the importance of coordinating efforts internationally to control TB. PMID:9795580

  8. Vitamin D status and incidence of tuberculosis among contacts of pulmonary tuberculosis patients.

    PubMed

    Arnedo-Pena, A; Juan-Cerdán, J V; Romeu-García, A; García-Ferrer, D; Holguín-Gómez, R; Iborra-Millet, J; Gil-Fortuño, M; Gomila-Sard, B; Roach-Poblete, F

    2015-01-01

    A prospective cohort study was conducted from 2009 to 2012 to assess the relationship between serum baseline 25-hydroxivytamin D (vitamin D) status and the incidence of tuberculosis (TB) among 572 contacts of 89 pulmonary TB patients in Castellon, Spain. Three new cases of pulmonary TB occurred, with an incidence density of 3.6 per 1000 person-years. Mean vitamin D status was 13.7 ng/ml for cases and 25.7 ng/ml for non-cases. Vitamin D status showed a significant inverse association with TB incidence (adjusted HR 0.88, 95%CI 0.80-0.97). This result is in line with the hypothesis that vitamin D deficiency is associated with TB incidence.

  9. Co-Fe-Tb (202)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 2 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from B-Be-Fe to Co-W-Zr' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Co-Fe-Tb (202)' with the content:

  10. B-Fe-Tb (148)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 2 http://dx.doi.org/10.1007/9getType="URL"/> 'Systems from B-Be-Fe to Co-W-Zr' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'B-Fe-Tb (148)' with the content:

  11. Influence of a moderate physical activity intervention on red cell deformability in patients suffering from chronic obstructive pulmonary disease (COPD).

    PubMed

    Ahmad, Basit; Ferrari, Nina; Montiel, Georgina; Bloch, Wilhelm; Raabe-Oetker, Anke; Skrobala, Nina; Brixius, Klara

    2013-07-01

    The present study investigates whether a moderate physical activity intervention may alter red cell deformability (RCD) of patients suffering from chronic obstructive pulmonary disease (COPD). Subjects (n = 10; age: 62 ± 4; body-mass index (BMI): 25.8 ± 7.5) performed a training regimen for 10 weeks. In the beginning of the study and after the training period, COPD patients underwent a WHO cycle ergometry test. Venous blood samples were taken before (T0), immediately after (T1) and 30 min after (T2) the intervention. RCD was measured with the laser-assisted optical rotational cell analyzer (LORCA). Significant improvements of the RCD were detected. The semi-maximal shear stress increased significantly. Acute exhaustion had no effect on RCD. Thus, the training period of 10 weeks influenced RCD.

  12. Simulating pulmonary vein activity leading to atrial fibrillation using a rule-based approach on realistic anatomical data.

    PubMed

    Reumann, M; Bohnert, J; Doessel, O

    2006-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia leading to a high rate of stroke. The underlying mechanisms of initiation and maintenance of AF are not fully understood. Several findings suggest a multitude of factors to leave the atria vulnerable to AF. In this work, a rule-based approach is taken to simulate the initiation of AF in a computer model for the purpose of generating a model with which the influence of anatomical structures, electrophysiological properties of the atria and arrhythmogenic activity can be evaluated. Pulmonary vein firing has been simulated leading to AF in 65.7 % of all simulations. The excitation pattern generated resemble chaotic excitation behavior, which is characteristic for AF as well as stable reentrant circuits responsible for atrial flutter. The findings compare well with literature. In future, the presented computer model of AF can be used in therapy planning such as ablation therapy or overdrive pacing.

  13. Microscopic examination and smear negative pulmonary tuberculosis in Ethiopia

    PubMed Central

    Keflie, Tibebe Seyoum; Ameni, Gobena

    2014-01-01

    Introduction Tuberculosis causes illness among millions of people each year and ranks as the second leading cause of death from infectious disease worldwide. The aim of this study was to investigate the detection rate of microscopic examination and estimate risk of transmission of TB by smear negative pulmonary TB patients. Methods A cross-sectional study and retrospective data analysis on TB were undertaken in Northwest Shewa, Ethiopia. Microscopic examination, bacterial culture and PCR were performed. The statistical analysis was made by using STATA software version 10. Results A total of 92 suspected TB cases was included in the study. Of these, 27.17% (25/92) were positive for microscopic examination and 51% (47/92) for culture. The sensitivity and specificity of microscopic examination with 95% CI were 48.94% (34.08% to 63.93%) and 95.56% (84.82 to 99.33%), respectively. The positive and negative predictive values were 92% (73.93% to 98.78%) and 64.18% (51.53% to 75.53%), respectively. Of 8150 pulmonary TB cases in the retrospective study, 58.9% was smear negative. The proportion of TB-HIV co-infection was 28.66% (96/335). Conclusion The sensitivity of microscopic examination was 48.94% which was very low. The poor sensitivity of this test together with the advent of HIV/AIDS elevated the prevalence of smear negative pulmonary TB. This in turn increased the risk of TB transmission. PMID:25810798

  14. PULMONARY LOCALIZATION AND EXPRESSION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) IN HEALTHY OR HYPERTENSIVE RATS EXPOSED TO PARTICULATE MATTER (PM)

    EPA Science Inventory

    PULMONARY LOCALIZATION AND EXPRESSION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) IN HEALTHY OR HYPERTENSIVE RATS EXPOSED TO PARTICULATE MATTER (PM). GS Backus1, R Vincent2, UP Kodavanti2, 1Curriculum in Toxicology, UNC, Chapel Hill; 2NHEERL, ORD, US EPA, Research Triangle Park,...

  15. Microparticulate/Nanoparticulate Powders of a Novel Nrf2 Activator and an Aerosol Performance Enhancer for Pulmonary Delivery Targeting the Lung Nrf2/Keap-1 Pathway.

    PubMed

    Muralidharan, Priya; Hayes, Don; Black, Stephen M; Mansour, Heidi M

    2016-01-01

    This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF:D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode. Regional targeted deposition using design of experiments (DoE) for in vitro predictive lung modeling based on aerodynamic properties was tailored based on composition and spray drying parameters. These findings indicate the significant potential of using D-Man in spray drying to improve particle formation and aerosol performance of small molecule with a relatively low melting point. These respirable microparticles/nanoparticles in the solid-state exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device. Using in vitro predictive lung deposition modeling, the aerosol deposition patterns of these particles show the capability to reach lower airways to treat inflammation in this region in pulmonary diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), and pulmonary endothelial disease.

  16. Surfactant protein D, Club cell protein 16, Pulmonary and activation-regulated chemokine, C-reactive protein, and Fibrinogen biomarker variation in chronic obstructive lung disease.

    PubMed

    Lock-Johansson, Sofie; Vestbo, Jørgen; Sorensen, Grith Lykke

    2014-11-25

    Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction. The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessment of patients, prediction of risk, and guidance of treatment. The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD. The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease and hard clinical outcomes, their modification by interventions, and whether changes in clinical outcomes are reflected by changes in the biomarker.

  17. Gender differentials of pulmonary tuberculosis transmission and reactivation in an endemic area

    PubMed Central

    Jiménez‐Corona, M‐E; García‐García, L; DeRiemer, K; Ferreyra‐Reyes, L; Bobadilla‐del‐Valle, M; Cano‐Arellano, B; Canizales‐Quintero, S; Martínez‐Gamboa, A; Small, P M; Sifuentes‐Osornio, J; Ponce‐de‐León, A

    2006-01-01

    Background In most low income countries there are twice as many cases of tuberculosis (TB) reported among men than among women, a difference commonly attributed to biological and epidemiological characteristics as well as socioeconomic and cultural barriers in access to health care. The World Health Organization has encouraged gender specific comparisons in TB rates to determine whether women with TB are less likely than men with TB to be diagnosed, reported, and treated. A study was undertaken to identify gender based differences in patients with pulmonary TB and to use this information to improve TB control efforts. Methods Individuals with a cough for more than 2 weeks in southern Mexico were screened from March 1995 to April 2003. Clinical and mycobacteriological information (isolation, identification, drug susceptibility testing and IS6110 based genotyping, and spoligotyping) was collected from those with bacteriologically confirmed pulmonary TB. Patients were treated in accordance with official norms and followed to ascertain treatment outcome, retreatment, and vital status. Results 623 patients with pulmonary TB were enrolled. The male:female incidence rate ratio for overall, reactivated, and recently transmitted disease was 1.58 (95% CI 1.34 to 1.86), 1.64 (95% CI 1.36 to 1.98), and 1.41 (95% CI 1.01 to 1.96), respectively. Men were more likely than women to default from treatment (adjusted OR 3.30, 95% CI 1.46 to 7.43), to be retreated (hazard ratio (HR) 3.15, 95% CI 1.38 to 7.22), and to die from TB (HR 2.23, 95% CI 1.25 to 3.99). Conclusions Higher rates of transmitted and reactivated disease and poorer treatment outcomes among men are indicators of gender differentials in the diagnosis and treatment of pulmonary TB, and suggest specific strategies in endemic settings. PMID:16449260

  18. Extra-pulmonary tuberculosis in Saudi Arabia.

    PubMed

    Al-Otaibi, Fawzia; El Hazmi, Malak M

    2010-01-01

    Studies from developed countries have reported that extra-pulmonary tuberculosis (EPTB) is on the rise due to the human immunodeficiency virus (HIV) epidemic. However, similar studies from high-burden countries with low prevalence of HIV like Saudi Arabia are lacking. Therefore, we conducted this study to investigate demographic and clinical characteristics of patients with pulmonary and extra-pulmonary tuberculosis. A retrospective analysis was carried out on all patients (n=431) with a culture - proven diagnosis of tuberculosis seen at University teaching hospital, Riyadh, Saudi Arabia from January 2001 to December 2007. A total of 183 (42.5%) pulmonary tuberculosis (PTB) and 248 (57.5%) extra-pulmonary TB (EPTB) cases were compared in terms of age, sex, and nationality. There were 372 Saudis (SA) (86.3%) and the remaining non-Saudis (NSA) 59 (13.7%). The age distribution of the PTB patients had a bimodal distribution. EPTB was more common at young age (20-29 years). The proportion of EPTB cases was significantly higher among NSA patients (72.9%) compared to SA patients (55.1%). Females had higher proportion (59.5%) of EPTB than males (55.6%). The most common site was lymph node tuberculosis (42%). In conclusion, our data suggest that EPTB was relatively common in younger age, female gender and NSA. Tuberculosis (TB) control program may target those populations for EPTB case-finding.

  19. Antiretroviral Treatment Scale-Up and Tuberculosis Mortality in High TB/HIV Burden Countries: An Econometric Analysis

    PubMed Central

    Yan, Isabel; Bendavid, Eran; Korenromp, Eline L.

    2016-01-01

    Introduction Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries. Methods We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects. Results Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (p<0.001), and 31% fewer deaths in 2011. TB mortality was higher at higher HIV prevalence (p<0.001), but not related to coverage of isoniazid preventive therapy, cotrimoxazole preventive therapy, or other covariates. Conclusion This econometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data. PMID:27536864

  20. Multidrug-Resistant Tuberculosis in Patients with Chronic Obstructive Pulmonary Disease in China

    PubMed Central

    Zhao, Jiang-nan; Zhang, Xian-xin; He, Xiao-chun; Yang, Guo-ru; Zhang, Xiao-qi; Xin, Wen-gen; Li, Huai-chen

    2015-01-01

    Background Relatively little is known about the specific relationship and impact from chronic obstructive pulmonary disease (COPD) on multidrug-resistant tuberculsosis (MDR-TB). Methods We conducted a retrospective study included patients aged ≥40 years with a confirmed pulmonary TB at three tertiary hospitals (Shandong, China) between January 2011 and October 2014. Univariable and multivariable analyses were performed to identify the relationship of MDR-TB and COPD. Results A total of 2164 patients aged ≥ 40 years with available results of drug susceptibility test (DST) and medical records were screened for this study: 268 patients with discharge diagnosis of COPD and 1896 patients without COPD. Overall, 14.2% of patients with COPD and 8.5% patients without COPD were MDR-TB. The rate of MDR-TB were significantly higher in patients with COPD (P<0.05). Migrant (odds ratios (OR) 1.32, 95% confidence interval (CI) 1.02–1.72), previous anti-TB treatment (OR 4.58, 95% CI 1.69–12.42), cavity (OR 2.33, 95% CI 1.14–4.75), and GOLD stage (OR 1.86, 95% CI 1.01–2.93) were the independent predictors for MDR-TB among patients with COPD. Conclusions MDR-TB occurs more frequently in patients with underlying COPD, especially those with being migrant, previous anti-TB therapy, cavity and severe airway obstruction. PMID:26284920

  1. TB vaccine development and the End TB Strategy: importance and current status.

    PubMed

    Fletcher, Helen A; Schrager, Lewis

    2016-04-01

    TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates.

  2. AMP‐activated protein kinase inhibits Kv1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation

    PubMed Central

    Moral‐Sanz, Javier; Mahmoud, Amira D.; Ross, Fiona A.; Eldstrom, Jodene; Fedida, David; Hardie, D. Grahame

    2016-01-01

    Key points Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (Kv) in pulmonary arterial smooth muscle by hypoxia, although the precise molecular mechanisms have been unclear.AMP‐activated protein kinase (AMPK) has been proposed to couple inhibition of mitochondrial metabolism by hypoxia to acute hypoxic pulmonary vasoconstriction and progression of pulmonary hypertension.Inhibition of complex I of the mitochondrial electron transport chain activated AMPK and inhibited Kv1.5 channels in pulmonary arterial myocytes.AMPK activation by 5‐aminoimidazole‐4‐carboxamide riboside, A769662 or C13 attenuated Kv1.5 currents in pulmonary arterial myocytes, and this effect was non‐additive with respect to Kv1.5 inhibition by hypoxia and mitochondrial poisons.Recombinant AMPK phosphorylated recombinant human Kv1.5 channels in cell‐free assays, and inhibited K+ currents when introduced into HEK 293 cells stably expressing Kv1.5.These results suggest that AMPK is the primary mediator of reductions in Kv1.5 channels following inhibition of mitochondrial oxidative phosphorylation during hypoxia and by mitochondrial poisons. Abstract Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (Kv) in pulmonary arterial smooth muscle cells that is mediated by the inhibition of mitochondrial oxidative phosphorylation. We sought to determine the role in this process of the AMP‐activated protein kinase (AMPK), which is intimately coupled to mitochondrial function due to its activation by LKB1‐dependent phosphorylation in response to increases in the cellular AMP:ATP and/or ADP:ATP ratios. Inhibition of complex I of the mitochondrial electron transport chain using phenformin activated AMPK and inhibited Kv currents in pulmonary arterial myocytes, consistent with previously reported effects of mitochondrial inhibitors. Myocyte

  3. Dramatic effect of redox pre-treatments on the CO oxidation activity of Au/Ce(0.50)Tb(0.12)Zr(0.38)O(2-x) catalysts prepared by deposition-precipitation with urea: a nano-analytical and nano-structural study.

    PubMed

    del Río, Eloy; López-Haro, Miguel; Cíes, José M; Delgado, Juan J; Calvino, José J; Trasobares, Susana; Blanco, Ginesa; Cauqui, Miguel A; Bernal, Serafín

    2013-08-04

    Nano-structural and nano-analytical studies show that the dramatic difference in CO oxidation activity observed between two Au/Ce0.50Tb0.12Zr0.38O2-x samples prepared by deposition-precipitation with urea and further activated under oxidising or reducing conditions is due to the poisoning effect of a very thin layer of carbon grown on the pre-reduced catalyst.

  4. Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.

    PubMed

    Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi

    2013-01-01

    High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.

  5. Upper extremity acute compartment syndrome during tissue plasminogen activator therapy for pulmonary embolism in a morbidly obese patient

    PubMed Central

    Tuna, Serkan; Duymus, Tahir Mutlu; Mutlu, Serhat; Ketenci, Ismail Emre; Ulusoy, Ayhan

    2015-01-01

    Introduction Deep vein thrombosis (DVT) and pulmonary embolism (PE) are more frequently observed in morbidly obese patients. Tissue plasminogen activator (tPA) is a thrombolytic agent which dissolves the thrombus more rapidly than conventional heparin therapy and reduces the mortality and morbidity rates associated with PE. Compartment syndrome is a well-known and documented complication of thrombolytic treatment. In awake, oriented and cooperative patients, the diagnosis of compartment syndrome is made based on clinical findings including swelling, tautness, irrational and continuous pain, altered sensation, and severe pain due to passive stretching. These clinical findings may not be able to be adequately assessed in unconscious patients. Presentation of case In this case report, we present compartment syndrome observed, for which fasciotomy was performed on the upper right extremity of a 46-year old morbidly obese, conscious female patient who was receiving tPA due to a massive pulmonary embolism. Discussion Compartment syndrome had occurred due to the damage caused by the repeated unsuccessful catheterisation attempts to the brachial artery and the accompanying tPA treatment. Thus, the bleeding that occurred in the volar compartment of the forearm and the anterior compartment of the arm led to acute compartment syndrome (ACS). After relaxation was brought about in the volar compartment of the forearm and the anterior compartment of the arm, the circulation in the limb was restored. Conclusion As soon as the diagnosis of compartment syndrome is made, an emergency fasciotomy should be performed. Close follow-up is required to avoid wound healing problems after the fasciotomy. PMID:25618841

  6. Green photoluminescence from Zn3N2:Tb films prepared by magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Zhang, Z.-X.; Pan, X.-J.; Liu, L.-X.; Ma, Z.-W.; Zhao, H.-T.; Jia, L.; Xie, E.-Q.

    2009-01-01

    Terbium (Tb)-doped Zn3N2 thin films were prepared on glass and Si substrates by direct current magnetron sputtering in a mixture of pure argon and nitrogen gases. Glancing incidence x-ray diffraction patterns indicated that Zn3N2:Tb thin films were of cubic structure. Raman spectra showed only two Raman-active phonon modes located at 258 and 565 cm-1. The indirect optical band gap of Zn3N2:Tb was determined as 2.4 eV. The sharp characteristic emission lines corresponding to Tb3+ intra-4f shell transitions were resolved in the photoluminescence spectra at room temperature. Those results suggest that Tb-doped Zn3N2 may be a suitable material for visible optoelectronic devices.

  7. Pulmonary Embolism

    MedlinePlus

    ... for the Public » Health Topics » Pulmonary Embolism Explore Pulmonary Embolism What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Arrhythmia Deep Vein Thrombosis Lung VQ Scan Overweight and Obesity Send a ...

  8. The management for tuberculosis control in Greater London in comparison with that in Osaka City: lessons for improvement of TB control management in Osaka City urban setting.

    PubMed

    Ohkado, Akihiro; Williams, Gini; Ishikawa, Nobukatsu; Shimouchi, Akira; Simon, Carter

    2005-07-01

    Network are major key functioning bodies to involve relevant professionals as wide as possible. The specialist TB nurses play key roles for TB case management across Greater London, while in Osaka City, TB control is characterised with strong leadership and commitment of Osaka City Government for the TB control programme. The Osaka City Public Health Centre (PHC) takes initiatives to expand "Cohort Analysis and Case Management Conferences" at each of the 24 Ward Health and Welfare Centres as well as "DOTS Conferences" at hospitals for improvement of case management by physicians and nurses at hospitals as well as by the health centre staff. Public health nurses (PHNs) play very important roles for TB case management as frontline in Osaka City. Comparing the TB control in both cities, the following suggested recommendations are made to both cities for further improvement. Four suggested recommendations to Osaka City are: more resource re-allocation to community-based TB care than to hospital-based TB care should be done; Cohort Analysis and Case Management Conferences should be strengthened through involving more multi-disciplinary sectors; specialist TB PHN at each of the 24 Ward Health and Welfare Centres should be assigned in order to concentrate more on TB control activities; and accessibility to laboratory data such as drug susceptibility test for health centre staff should be improved. Two suggested recommendations to Greater London are: screening for TB high-risk group like homeless people should be strengthened, and regular sector-wide multi-disciplinary case conferences for proper case management should be strengthened.

  9. Tunable luminescence properties and energy transfer in LaAl₁₁O₁₈:Eu,Tb phosphor.

    PubMed

    Mendhe, M S; Puppalwar, S P; Dhoble, S J

    2016-05-01

    Eu(2+) and Tb(3+) singly doped and co-doped LaAl11O18 phosphors were prepared by a combustion method using urea as a fuel. The phase structure and photoluminescence (PL) properties of the prepared phosphors were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence excitation and emission spectra. When the content of Eu(2+) was fixed at 0.01, the emission chromaticity coordinates could be adjusted from blue to green region by tuning the contents of Tb(3+) ions from 0.01 to 0.03 through an energy transfer (ET) process. The fluorescence data collected from the samples with different contents of Tb(3+) into LaAl11O18: Eu, show the enhanced green emission at 545 nm associated with (5)D(4)-(7)F(5) transitions of Tb(3+). The enhancement was attributed to ET from Eu(2+) to Tb(3+), and therefore Eu(2+) ion acts as a sensitizer (an energy donor) while Tb(3+) ion as an activator. The ET from Eu(2+) to Tb(3+) is performed through dipole-dipole interaction. The ET efficiency and critical distance were also calculated. The present Eu(2+)-Tb(3+) co-doped LaAl11O18 phosphor will have potential application for UV convertible white light-emitting diodes.

  10. Adenosine deaminase in CSF and pleural fluid for diagnosis of tubercular meningitis and pulmonary tuberculosis.

    PubMed

    Nepal, A K; Gyawali, N; Poudel, B; Mahato, R V; Lamsal, M; Gurung, R; Baral, N; Majhi, S

    2012-12-01

    Tuberculosis (TB) is one of the most common infectious diseases in developing countries including Nepal. Delay in diagnosis and treatment of tuberculosis results in poor prognosis of the disease. This study was conducted to estimate diagnostic cut off values of Adenosine Deaminase (ADA) in cerebrospinal fluid (CSF) and pleural fluid and to evaluate the sensitivity, specificity, positive and negative predictive values ofADA in pleural fluid and CSF from patients with tuberculous and non-tuberculous disease. A total of 98 body fluid (CSF: 24, Pleural fluid: 74) specimens were received for the estimation of ADA. ADA activity was measured at 37 degrees C by spectrophotometric method of Guisti and Galanti, 1984 at 625nm wavelength. Among the patients enrolled for the study subjects for which CSF were received (n = 24) included 8 tuberculous meningitis (TBM), and 16 non-tubercular meningitis (NTM). Pleural fluid samples (n = 74) were received from 19 pulmonary TB with pleural effusion, 17 PTB without pleural effusion and 37 of non-tuberculous disease patients. CSF ADA activity were (11. 1 +/- 2.03 IU/L) and (5.3 +/- +1.89 IU/L) (p <00001) in TM and non-NTM groups and Pleural fluid ADA activity were (10 +/- 22.18 IU/L) and (23.79 +/- 11.62 IU/L) (p < 0.001) in PTB and non-TB groups respectively. ADA test in body fluids, which is simple, cost-effective and sensitive, specific for the tubercular disease is recommended to perform before forwarding the cumbersome and expensive procedures like culture and PCR for TB diagnosis.

  11. Pulmonary blastomycosis.

    PubMed

    Bariola, J Ryan; Vyas, Keyur S

    2011-12-01

    Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. In rare cases pulmonary blastomycosis is associated with the acute respiratory distress syndrome. Blastomycosis can present as isolated pulmonary disease or along with coexisting extrapulmonary disease that usually will involve the skin, bony structures, genitourinary tract, or central nervous system. Diagnosis is largely based on isolation of the organism via culture or visualization of the organism in clinical specimens. Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis.

  12. Snapshot of Quantiferon TB gold testing in Northern Mexico.

    PubMed

    González-Salazar, F; Vargas-Villarreal, J; Garcialuna-Martínez, F J; Rivera, G; Moreno-Treviño, M G; Montfort-Gardeazabal, J M; Garcialuna-Martínez, E

    2011-12-01

    Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection.

  13. Barriers to managing TB in emergency departments.

    PubMed

    Morton, Rachel

    Improved management of tuberculosis is a key priority for Public Health England due to unacceptably high rates of the disease in the UK, particularly in London and other major cities. A survey of 20 staff in the acute medical unit at Queen Alexandra Hospital, Portsmouth, explored potential barriers to early TB detection and infection control in busy emergency departments. Low awareness and little familiarity with TB among many emergency admissions staff increased the likelihood of transmission from undiagnosed patients in crowded waiting areas. The study suggested regular updates on TB so staff could refresh their knowledge and awareness, and help improve TB detection and infection control.

  14. Cross-talk between p(38)MAPK and G iα in regulating cPLA 2 activity by ET-1 in pulmonary smooth muscle cells.

    PubMed

    Chakraborti, Sajal; Chowdhury, Animesh; Chakraborti, Tapati

    2015-02-01

    Endothelin-1 (ET-1) is known as the most potent vasoconstrictor yet described. Infusion of ET-1 into isolated rabbit lung has been shown to cause pulmonary vasoconstriction with the involvement of arachidonic acid metabolites. Given the potency of arachidonic acid metabolites, the activity of phospholipase A2 must be tightly regulated. Herein, we determined the mechanisms by which ET-1 stimulates cPLA2 activity during ET-1 stimulation of bovine pulmonary artery smooth muscle cells. We demonstrated that (i) treatment of bovine pulmonary artery smooth muscle cells with ET-1 stimulates cPLA2 activity in the cell membrane; (ii) ET-1 caused increase in O 2 (·-) production occurs via NADPH oxidase-dependent mechanism; (iii) ET-1-stimulated NADPH oxidase activity is markedly prevented upon pretreatment with PKC-ζ inhibitor, indicating that PKC-ζ plays a prominent role in this scenario; (iv) ET-1-induced NADPH oxidase-derived O 2 (·-) stimulates an aprotinin sensitive protease activity due to prominent increase in [Ca(2+)]i; (v) the aprotinin sensitive protease plays a pivotal role in activating PKC-α, which in turn phosphorylates p(38)MAPK and subsequently Giα leading to the activation of cPLA2. Taken together, we suggest that cross-talk between p(38)MAPK and Giα with the involvement of PKC-ζ, NADPH oxidase-derived O 2 (·-) , [Ca(2+)]i, aprotinin-sensitive protease and PKC-α play a pivotal role for full activation of cPLA2 during ET-1 stimulation of pulmonary artery smooth muscle cells.

  15. Is tuberculosis a lymphatic disease with a pulmonary portal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis (TB) is commonly viewed as a pulmonary disease, in which infection, persistence, induction of pathology and bacterial expulsion all occur in the lungs. In this model, enlarged lymph nodes represent reactive adenitis and spread of organisms to extrapulmonary sites results in a non-transm...

  16. Outcome of pulmonary tuberculosis treatment in the tertiary care setting -- Toronto 1992/93

    PubMed Central

    Wobeser, W; Yuan, L; Naus, M

    1999-01-01

    BACKGROUND: Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB control programs. This study was carried out to assess treatment completion for active cases of pulmonary TB in Toronto. METHODS: Consecutive cases of culture-proven pulmonary TB were obtained from the microbiology laboratories of 5 university-affiliated tertiary care centres in Toronto in 1992/93. A standard data-collection tool was used to abstract information from inpatient and outpatient charts. For patients who were transferred to other treatment centres or lost to follow-up, the local health unit was contacted for information about treatment completion. If incomplete information was obtained from these sources, data from the provincial Reportable Disease Information System were also reviewed. The main outcome analysed was treatment outcome, with cases classified as completed (record of treatment completion noted), transferred (patient transferred to another centre but no treatment results available), defaulted (record of defaulting in patient chart but no record of treatment completion elsewhere, or patient still receiving treatment more than 15 months after diagnosis) or dead (patient died before treatment completion). RESULTS: Of the 145 patients 84 (58%) completed treatment, 25 (17%) died, 22 (15%) defaulted and 14 (10%) were transferred. The corresponding values for the 22 patients with HIV coinfection were 6 (27%), 5 (23%), 8 (36%) and 3 (14%). Independent predictors of failure to complete treatment were injection drug use (adjusted odds ratio [OR] 5.7, 95% confidence interval [CI] 1.5 to 22.0), HIV infection (adjusted OR 4.6, 95% CI 1.4 to 14.7) and adverse drug reaction (adjusted OR 2.9, 95% CI 1.1 to 7.9). Independent predictors of death included age more than 50 years (adjusted OR 16.7, 95% CI 2.6 to 105.1), HIV infection (adjusted OR 16.1, 95% CI 3.9 to 66.4), immunosuppressive therapy (adjusted OR 8.0, 95% CI 1.9 to 34.4) and infection with

  17. Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Brusse-Keizer, Marjolein; VanderValk, Paul; van der Zanden, Rogier W; Nijdam, Lars; van der Palen, Job; Hendrix, Ron; Movig, Kris

    2015-01-01

    Background Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations activity in sputum than patients with a concentration ≥MIC90. Methods In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum. Results We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations activity and sputum amoxicillin concentrations activity did not differ between those with sputum amoxicillin concentrations

  18. Reversible pulmonary trunk banding. IX. G6PD activity of adult goat myocardium submitted to ventricular retraining

    PubMed Central

    Assad, Renato Samy; Miana, Leonardo Augusto; Fonseca-Alaniz, Miriam Helena; Abduch, Maria Cristina Donadio; da Silva, Gustavo José Justo; de Oliveira, Fernanda Santos; Moreira, Luiz Felipe Pinho; Krieger, José Eduardo

    2013-01-01

    Objective Increased glucose 6-phosphate dehydrogenase activity has been demonstrated in heart failure. This study sought to assess myocardial glucose 6-phosphate dehydrogenase activity in retraining of the subpulmonary ventricle of adult goats. Methods Eighteen adult goats were divided into three groups: traditional (fixed banding), sham, and intermittent (adjustable banding, daily 12-hour systolic overload). Systolic overload (70% of systemic pressure) was maintained during a 4-week period. Right ventricle, pulmonary artery and aortic pressures were measured throughout the study. All animals were submitted to echocardiographic and hemodynamic evaluations throughout the protocol. After the study period, the animals were killed for morphological and glucose 6-phosphate dehydrogenase activity assessment. Results A 55.7% and 36.7% increase occurred in the intermittent and traditional right ventricle masses, respectively, when compared with the sham group (P<0.05), despite less exposure of intermittent group to systolic overload. No significant changes were observed in myocardial water content in the 3 groups (P=0.27). A 37.2% increase was found in right ventricle wall thickness of intermittent group, compared to sham and traditional groups (P<0.05). Right ventricle glucose 6-phosphate dehydrogenase activity was elevated in the traditional group, when compared to sham and intermittent groups (P=0.05). Conclusion Both study groups have developed similar right ventricle hypertrophy, regardless less systolic overload exposure of intermittent group. Traditional systolic overload for adult subpulmonary ventricle retraining causes upregulation of myocardial glucose 6-phosphate dehydrogenase activity. It may suggest that the undesirable "pathologic systolic overload" is influenced by activation of penthose pathway and cytosolic Nicotinamide adenine dinucleotide phosphate availability. This altered energy substrate metabolism can elevate levels of free radicals by Nicotinamide

  19. A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

    PubMed Central

    2012-01-01

    Background There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. Methods In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Results Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Conclusions Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB. PMID:22239941

  20. A single-phase full-color phosphor based on Ba3MgSi2O8 co-activated with Eu2+, Tb3+, and Mn2+

    NASA Astrophysics Data System (ADS)

    Birkel, Alexander; DeCino, Nicholas A.; Cozzan, Clayton; Mikhailovsky, Alexander A.; Hong, Byung-Chul; Seshadri, Ram

    2015-10-01

    We present a rapid and energy-efficient microwave-assisted approach to prepare a single-phase full-color phosphor based on Ba3MgSi2O8. The samples were prepared using a citric acid based sol-gel preparation pathway with a microwave-assisted heating step, which reduces the time required for the final heat treatment to less than 30 min. Thermogravimetric analysis was utilized to optimize the solution-based preparation prior to microwave heating. The structural properties of the obtained luminescent materials have been thoroughly investigated by means of X-ray powder diffraction and Rietveld analyses. To study the optical behavior, the excitation and emission spectra were recorded. Full-color emission is achieved using Eu2+ (blue), Tb3+ (green), and Mn2+ (red) as the activator ions. The thermally robust emission was investigated using temperature-dependent luminescence spectroscopy. The energy-transfer processes within the samples were studied using time-dependent spectroscopy, and the quantum yield of this true color phosphor as a function of the composition was determined.

  1. Implementation challenges of a TB programme in rural northern mozambique: evaluation of 2012–2013 outcomes

    PubMed Central

    Wikman-Jorgensen, Philip Erik; Morales-Cartagena, Alejandra; Llenas-García, Jara; Pérez-Porcuna, Tomàs Maria; Hobbins, Michael; Ehmer, Jochen; Mussa, Manuel Aly; Abellana, Rosa; Ascaso, Carlos

    2015-01-01

    Background We aimed to identify challenges and to propose solutions for the implementation of tuberculosis (TB) programmes in rural Sub-Saharan Africa (SSA) by evaluating the outcomes of the TB programme in the Ancuabe district in rural Northern Mozambique. Methods Retrospective descriptive study of the patients included in the TB programme in 2012–2013. Follow-up was continued till June 2014. Results Three hundred nineteen patients were registered, 62.1% male, mean age 36.3 (SD 14.4), estimated case detection rate (eCDR) of 24.24%. Two hundred seventy-two were new cases, 21 transferred-in, 11 back after lost to follow-up (LTFU), 10 relapsing TB, 5 previous treatment failures. 94.4% were tested for Human immunodeficiency virus (HIV), 41.9% HIV-positive. 87.5% of the new cases were pulmonary TB (PTB), 43.4% were HIV co-infected. Initial sputum results were available in 207 cases, with 145 smear-positive (SP) cases. Outcomes of new cases: 122 (44.9%) LTFU, 55 (20.2%) cured, 43 (15.8%) treatment completed (98–36%-treatment success), 31 (11.4%) died, 19 (7%) transferred out and 2 (0.7%) failures. Conclusions A low eCDR and high proportion of LTFU demonstrate that few patients were identified and had a low probability of complete treatment, suggesting a fragile health system. This raises the hypothesis that, probably, to improve TB health care in rural SSA, interventions should aim at improving health systems. Special attention should be given to social protection and compensation of the financial burden associated with TB. PMID:26239760

  2. Type 2 diabetes mellitus coincident with pulmonary or latent tuberculosis results in modulation of adipocytokines.

    PubMed

    Pavan Kumar, Nathella; Nair, Dina; Banurekha, V V; Dolla, Chandrakumar; Kumaran, Paul; Sridhar, Rathinam; Babu, Subash

    2016-03-01

    Type 2 diabetes mellitus (T2DM) is recognized as major risk factor for the progress of active pulmonary tuberculosis (PTB), although the mechanistic link between diabetes and tuberculosis remains poorly characterized. Moreover, the influence of poorly controlled diabetes on the baseline levels of adipocytokines in the context of tuberculosis has not been explored in detail. To characterize the influence of coexistent DM on adipocytokine levels in pulmonary or latent TB (LTB), we examined circulating levels of adipocytokines in the plasma of individuals with PTB-DM or LTB-DM and compared them with those without DM (PTB or LTB). PTB-DM or LTB-DM is characterized by diminished circulating levels of adiponectin and adipsin and/or heightened circulating levels of leptin, visfatin and PAI-1. In addition, adiponectin and adipsin exhibit a significant negative correlation, whereas leptin, visfatin and PAI-1 display a significant positive correlation with HbA1C levels and random blood glucose levels. Therefore, our data reveal that PTB-DM or LTB-DM is characterized by alterations in the systemic levels of adipocytokines, indicating that altered adipose tissue inflammation underlying Type 2 diabetes potentially contributes to pathogenesis of TB disease.

  3. A First Insight into High Prevalence of Undiagnosed Smear-Negative Pulmonary Tuberculosis in Northern Ethiopian Prisons: Implications for Greater Investment and Quality Control

    PubMed Central

    Biadglegne, Fantahun; Rodloff, Arne C.; Sack, Ulrich

    2014-01-01

    Background Tuberculosis (TB) transmission in prisons poses significant risks to inmates as well as the general population. Currently, there are no data on smear-negative pulmonary TB cases in prisons and by extension no data on the impact such cases have on TB incidence. This study was designed to obtain initial data on the prevalence of smear-negative cases of TB in prisons as well as preliminary risk factor analysis for such TB cases. Methods This cross-sectional survey was conducted in November 2013 at eight main prisons located in the state of Amhara, Ethiopia. Interviews using a structured and pretested questionnaire were done first to identify symptomatic prisoners. Three consecutive sputum samples were collected and examined using acid fast bacilli (AFB) microscopy at the point of care. All smear-negative sputum samples were taken for culture and Xpert testing. Descriptive and multivariate analysis was done using SPSS version 16. Results Overall the prevalence of smear-negative pulmonary TB cases in the study prisons was 8% (16/200). Using multivariate analysis, a contact history to TB patients in prison, educational level, cough and night sweating were found to be predictors of TB positivity among smear-negative pulmonary TB cases (p≤ 0.05). Conclusions In the studied prisons, high prevalence of undiagnosed TB cases using AFB microscopy was documented, which is an important public health concern that urgently needs to be addressed. Furthermore, patients with night sweating, non-productive cough, a contact history with TB patients and who are illiterate merit special attention, larger studies are warranted in the future to assess the associations more precisely. Further studies are also needed to examine TB transmission dynamics by patients with smear-negative pulmonary TB in a prison setting. PMID:25203007

  4. Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure.

    PubMed

    Murthy, Shubha; Larson-Casey, Jennifer L; Ryan, Alan J; He, Chao; Kobzik, Lester; Carter, A Brent

    2015-08-01

    Alternative activation of alveolar macrophages is linked to fibrosis following exposure to asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a receptor for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling receptor for asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required for the development of asbestos-induced fibrosis. Compared with normal subjects, alveolar macrophages isolated from patients with asbestosis express higher amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold) and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold) and nearly 7-fold more active TGF-β1 in bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the polarization of macrophages to a profibrotic phenotype as mutation of these residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO. These observations demonstrate that a macrophage membrane protein regulates the fibrotic response to lung injury and suggest a novel target for therapeutic intervention.

  5. Health professionals as stigmatisers of tuberculosis: insights from community members and patients with TB in an urban district in Ghana.

    PubMed

    Dodor, Emmanuel Atsu; Kelly, Shona; Neal, Keith

    2009-05-01

    Health professionals are in a power category within any social setting so when they identify and label diseases with negative attributes, it can be recognised by society with discriminatory consequences for individuals affected in the community. This article reports how activities of health professionals, as perceived and construed by community members can be a basis of stigmatisation of patients with tuberculosis (TB) in society. One hundred individual interviews and 22 focus groups were held with community members and patients with TB, and the generated data analysed using the grounded theory techniques and procedures. Through examination of the words and statements of the participants, five inter-related ways by which activities of health professionals may expose patients with TB to stigmatisation in the community were identified: isolation and exclusionary practices; behaviours of health professionals towards patients with TB; public health discourse; food safety and hygiene practices and prohibition of full burial rites to those who died from TB. These activities are mirrored in the attitudes and behaviours of community members, and often become the basis of stigmatisation of individuals affected by TB in society. This may considerably contribute to diagnostic delay and low case finding in Ghana. Because, for fear of stigmatisation, community members who may be experiencing symptoms suggestive of TB may fail to go to the hospital. The stigma attached to TB in society may also contribute to the poor adherence to treatment seen among patients with TB in Ghana. To help to improve case finding and defaulter rate, the TB control programme should organise regular refresher courses in TB control and management for health professionals, and address the fear of infection by developing a national guidelines on how to prevent transmission of TB to health professionals within the hospital setting.

  6. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  7. [A case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis].

    PubMed

    Kimura, Yosuke; Kurosawa, Takayuki; Hosaka, Kiminori

    2014-09-01

    A case of pulmonary Mycobacterium kansasii infection with pleural effusion is very rare. We report a case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis. A 44-year-old man presented to a clinic with a productive cough, sputum, and loss of appetite for several months. Chest X-ray and chest computed tomography (CT) showed right pleural effusion, centrilobular nodules and infiltrative shadows with cavities in the bilateral lung fields. The direct smear examination showed positive acid-fast bacilli (Gaffky 5). He was referred to our hospital for suspected recurrent pulmonary tuberculosis. We started anti-tuberculosis drugs because pulmonary tuberculosis complicated with pleurisy was first suspected from the findings of high ADA level (78.6 IU/l) of the effusion and positive result of interferon-gamma release assay (QuantiFERON TB-2G). But Mycobacterium tuberculosis and M. avium complex was not identified by the polymerase chain reaction method and the culture of the sputum was negative. At a later date, Mycobacterium kansasii was detected by sputum culture. The patient was diagnosed as pulmonary Mycobacterium kansasii infection and treatment with anti-tuberculosis drugs including RFP resulted in a good clinical response. This case was a rare case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis.

  8. A two-strain TB model with multiple latent stages.

    PubMed

    Jabbari, Azizeh; Castillo-Chavez, Carlos; Nazari, Fereshteh; Song, Baojun; Kheiri, Hossein

    2016-08-01

    A two-strain tuberculosis (TB) transmission model incorporating antibiotic-generated TB resistant strains and long and variable waiting periods within the latently infected class is introduced. The mathematical analysis is carried out when the waiting periods are modeled via parametrically friendly gamma distributions, a reasonable alternative to the use of exponential distributed waiting periods or to integral equations involving ``arbitrary'' distributions. The model supports a globally-asymptotically stable disease-free equilibrium when the reproduction number is less than one and an endemic equilibriums, shown to be locally asymptotically stable, or l.a.s., whenever the basic reproduction number is greater than one. Conditions for the existence and maintenance of TB resistant strains are discussed. The possibility of exogenous re-infection is added and shown to be capable of supporting multiple equilibria; a situation that increases the challenges faced by public health experts. We show that exogenous re-infection may help established resilient communities of actively-TB infected individuals that cannot be eliminated using approaches based exclusively on the ability to bring the control reproductive number just below 1.

  9. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    PubMed

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required.

  10. What is Multidrug and Extensively Drug Resistant TB?

    MedlinePlus

    ... org > Lung Health and Diseases > Lung Disease Lookup > Tuberculosis (TB) What Is Multidrug and Extensively Drug Resistant TB? Multidrug-resistant tuberculosis ( MDR TB ) is a very dangerous form of ...

  11. TB in Correctional Facilities Is a Public Health Concern

    MedlinePlus

    ... component to TB elimination in the United States. Tuberculosis (TB) is a disease caused by bacteria that ... is essential to these efforts. More Information Reported Tuberculosis in the United States, 2012 TB in Correctional ...

  12. Protocol for studying cough frequency in people with pulmonary tuberculosis

    PubMed Central

    Bravard, Marjory A; Tracey, Brian H; López, José W; Comina, German; Zimic, Mirko; Coronel, Jorge; O'Neill Lee, Gwenyth; Caviedes, Luz; Luis Cabrera, Jose; Salas, Antonio; Ticona, Eduardo; Kirwan, Daniela E; Friedland, Jon S; Evans, Carlton A; Moore, David A; Gilman, Robert H

    2016-01-01

    Introduction Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. Methods This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. Ethics and dissemination Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed. PMID:27105713

  13. Characteristics and Treatment Outcomes of Patients with MDR and XDR Tuberculosis in a TB Referral Hospital in Beijing: A 13-Year Experience

    PubMed Central

    Wang, Qi; Hu, Yong Liang; Zhu, Baoli; Woo, Patrick C. Y.

    2011-01-01

    Background Information on treatment outcomes among hospitalized patients with multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are scarce in China. Methodology/Principal Findings We conducted this retrospective study to analyze the characteristics and treatment outcomes in MDR- and XDR-TB patients in the 309 Hospital in Beijing, China during 1996–2009. Socio-demographic and clinical data were retrieved from medical records and analyzed. Logistic regression analysis was performed to identify risk factors associated with poor treatment outcomes and Cox proportional hazards regression model was further used to determine risk factors associated with death in TB patients. Among the 3,551 non-repetitive hospitalized TB patients who had drug susceptibility testing (DST) results, 716 (20.2%) had MDR-TB and 51 (1.4%) had XDR-TB. A total of 3,270 patients who had medical records available were used for further analyses. Treatment success rates (cured and treatment completed) were 90.9%, 53.4% and 29.2% for patients with non-MDR-TB, patients with MDR-TB excluding XDR-TB and patients with XDR-TB, respectively. Independent risk factors associated with poor treatment outcomes in MDR-TB patients included being a migrant (adjusted OR = 1.77), smear-positivity at treatment onset (adjusted OR = 1.94) and not receiving 3 or more potentially effective drugs (adjusted OR = 3.87). Independent risk factors associated with poor treatment outcomes in XDR-TB patients were smear-positivity at treatment onset (adjusted OR = 10.42) and not receiving 3 or more potentially effective drugs (adjusted OR = 14.90). The independent risk factors associated with death in TB patients were having chronic obstructive pulmonary disease (adjusted HR = 5.25) and having hypertension (adjusted HR = 4.31). Conclusions/Significance While overall satisfactory treatment success for non-MDR-TB patients was achieved, more intensive efforts

  14. Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

    PubMed

    Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment.

  15. Estimating the cost of TB and its social impact on TB patients and their households.

    PubMed

    Onazi, O; Gidado, M; Onazi, M; Daniel, O; Kuye, J; Obasanya, O; Odusote, T; Gande, S

    2015-06-21

    Illness often poses a significant financial burden on individuals and their households, and tuberculosis (TB) is no exception. Although TB treatment is free in Nigeria, patients are likely to incur costs due to multiple visits during treatment. The purpose of this study was 1) to examine the health-seeking behaviour of TB patients and the costs borne by TB patients in Nigeria, and 2) to assess the social impact of TB disease on TB patients and their families/households. Of 260 TB patients surveyed, the majority (74.7%) were aged between 20 and 49 years. TB patients expended an average of US$52.02 (N = 8323.58, at the rate of US$1 = N = 160) per person on all visits associated with diagnosis and receipt of diagnostic test results. Overall, households experienced a shortfall of about US$57.30 (N = 9174.72) or 24.9% of income loss due to TB illness. Further analysis revealed that 9.7% of TB patients relied on children of school age or below to finance the costs of TB illness.

  16. Estimating the cost of TB and its social impact on TB patients and their households

    PubMed Central

    Onazi, O.; Gidado, M.; Onazi, M.; Daniel, O.; Kuye, J.; Obasanya, O.; Odusote, T.; Gande, S.

    2015-01-01

    Illness often poses a significant financial burden on individuals and their households, and tuberculosis (TB) is no exception. Although TB treatment is free in Nigeria, patients are likely to incur costs due to multiple visits during treatment. The purpose of this study was 1) to examine the health-seeking behaviour of TB patients and the costs borne by TB patients in Nigeria, and 2) to assess the social impact of TB disease on TB patients and their families/households. Of 260 TB patients surveyed, the majority (74.7%) were aged between 20 and 49 years. TB patients expended an average of US$52.02 (N = 8323.58, at the rate of US$1 = N = 160) per person on all visits associated with diagnosis and receipt of diagnostic test results. Overall, households experienced a shortfall of about US$57.30 (N = 9174.72) or 24.9% of income loss due to TB illness. Further analysis revealed that 9.7% of TB patients relied on children of school age or below to finance the costs of TB illness. PMID:26400384

  17. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis The most common species of fungus that causes ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Review Date 7/31/2016 Updated by: Jatin ...

  18. Pulmonary atresia

    MedlinePlus

    ... blood flow from the right ventricle (right side pumping chamber) to the lungs. In pulmonary atresia, a ... Reconstructing the heart as a single ventricle (1 pumping chamber instead of 2) Heart transplant Outlook (Prognosis) ...

  19. 'Z(S)-MDR-TB' versus 'Z(R)-MDR-TB': improving treatment of MDR-TB by identifying pyrazinamide susceptibility.

    PubMed

    Zhang, Ying; Chiu Chang, Kwok; Leung, Chi-Chiu; Wai Yew, Wing; Gicquel, Brigitte; Fallows, Dorothy; Kaplan, Gilla; Chaisson, Richard E; Zhang, Wenhong

    2012-07-01

    Indispensable for shortening treatment of drug-susceptible tuberculosis (TB), pyrazinamide (PZA, Z) is also essential in the treatment of multidrug-resistant (MDR)-TB. While resistance to PZA in MDR-TB is associated with poor treatment outcome, bacillary susceptibility to PZA along with the use of fluoroquinolone (FQ) and second-line injectable drugs (SLIDs) may predict improved treatment success in MDR-TB. Despite a high prevalence of PZA resistance among MDR-TB patients (10%-85%), PZA susceptibility testing is seldom performed because of technical challenges. To improve treatment of MDR-TB, we propose to: (i) classify MDR-TB into PZA-susceptible MDR-TB (Z(S)-MDR-TB) and PZA-resistant MDR-TB (Z(R)-MDR-TB); (ii) use molecular tests such as DNA sequencing (pncA, gyrA, rrs, etc.) to rapidly identify Z(S)-MDR-TB versus Z(R)-MDR-TB and susceptibility profile for FQ and SLID; (iii) refrain from using PZA in Z(R)-MDR-TB; and (iv) explore the feasibility of shortening the treatment duration of Z(S)-MDR-TB with a regimen comprising PZA plus at least two bactericidal agents especially new agents like TMC207 or PA-824 or delamanid which the bacilli are susceptible to, with one or two other agents. These measures may potentially shorten therapy, save costs, and reduce side effects of MDR-TB treatment.

  20. Magnetoresistance in nanostructured Tb/Ti and Tb/Si multilayers

    SciTech Connect

    Svalov, A. V.; Kurlyandskaya, G. V.; Vas'kovskiy, V. O.; Sorokin, A. N.; Diercks, D.

    2011-01-15

    Magnetic, magnetoresistive and structural properties were studied for [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers which were prepared by rf-sputtering. The thickness of the Tb layers varied from 1.5 to 12 nm. The thickness of 2 nm nonmagnetic spacers of Ti or Si was kept constant. Both anisotropic and isotropic magnetoresistance was observed in [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers. A decrease in the thickness of the terbium layers led to a decrease in the anisotropic contribution to the total magnetoresistance. The negative isotropic magnetoresistanse in [Tb/Ti]{sub n} and [Tb/Si]{sub n} multilayers can be attributed to the giant magnetoresistance (GMR) and/or high field isotropic magnetoresistance. The structure of the samples of both types enabled the existence of the GMR effect.

  1. Pulmonary Agenesis.

    PubMed

    Chawla, Rakesh K; Madan, Arun; Chawla, Aditya; Arora, Harsh Nandini; Chawla, Kiran

    2015-01-01

    Unilateral opaque lung with ipsilateral mediastinal shift is an uncommon cause of respiratory distress in newborn which can be found on simple radiograph of the chest. Pulmonary agenesis is a rare cause of unilateral opaque lung in the newborn. Nearly 50% cases of pulmonary agenesis are associated with other congenital defects including cardiovascular, skeletal, gastrointestinal or genitourinary systems. We report an infant with agenesis of the right lung associated with other congenital anomalies.

  2. Polymorphisms in the RANTES gene increase susceptibility to active tuberculosis in Tunisia.

    PubMed

    Ben-Selma, Walid; Harizi, Hedi; Bougmiza, Iheb; Ben Kahla, Imen; Letaief, Mahmoud; Boukadida, Jalel

    2011-10-01

    RANTES plays a pivotal role in attracting and activating various leukocyte populations that control Mycobacterium tuberculosis infection. The present study investigated the relationship between the RANTES polymorphisms (-28C/G; rs2280788, and -403G/A; rs2107538) and susceptibility to active tuberculosis (TB) in Tunisian populations. A total of 168 patients with pulmonary TB (pTB), 55 with extrapulmonary TB (epTB), and 150 control subjects were studied. Genotype analyses were carried out using polymerase chain reaction-restriction fragment length polymorphism method. We found that the -28 GG genotype was significantly associated with susceptibility to pTB (odds ratio [OR]=11.19; 95% confidence intervals [CI], 5.14-25; P corrected for the number of genotypes [Pc]=10(-8)) and epTB (OR=11.67; 95% CI, 4.74-29.33; Pc=10(-8)). However, the -28 CC genotype was found to be significantly associated with resistance to pTB (OR=0.08; 95% CI, 0.04-0.16; Pc=10(-8)) and epTB development (OR=0.11; 95% CI, 0.05-0.27; Pc=10(-8)). -403A allele was associated with increased risk development of epTB (OR=2.21; 95% CI, 1.18-4.14; p=0.007). G-G and A-C haplotypes and the AG/GC diplotype were associated with increase susceptibility to pTB (OR=7.88, 95% CI, 5.38-11.55; Pc=3.10(-8); OR=2.32, 95% CI, 1.32-4.11; Pc=3.10(-3); OR=13.26, 95% CI, 6.06-29.89; Pc=3.10(-8); respectively) and epTB (OR=6.64, 95% CI, 4-11.05; Pc=3.10(-8); OR=2.6, 95% CI, 1.26-5.35; Pc=12.10(-3); OR=11.26, 95% CI, 4.44-29.28; Pc=3.10(-8); respectively). Collectively, our findings suggested an association of the RANTES -28C/G and -403G/A functional polymorphisms with susceptibility to Mycobacterium tuberculosis infection in Tunisian populations.

  3. Sensitivity of the Quantiferon-Gold In-Tube Assay in Sputum Smear Positive TB Cases in Indonesia

    PubMed Central

    Rutherford, Merrin; Alisjahbana, Bachti; Maharani, Winni; Sampurno, Hedy; van Crevel, Reinout; Hill, Philip C.

    2010-01-01

    Background As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection. Methods and Findings We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results. Conclusions The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests. PMID:20711257

  4. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection.

    PubMed

    Hoff, Soren T; Peter, Jonathan G; Theron, Grant; Pascoe, Mellissa; Tingskov, Pernille N; Aggerbeck, Henrik; Kolbus, Daniel; Ruhwald, Morten; Andersen, Peter; Dheda, Keertan

    2016-03-01

    C-Tb, a novel Mycobacterium tuberculosis and 6-kDa early secretory antigenic target/10-kDa culture filtrate protein (ESAT-6/CFP-10)-specific skin test, has high specificity in bacille Calmette-Guerin-vaccinated healthy controls. However, the sensitivity of C-Tb has hitherto not been determined. The objective was to determine the sensitivity of C-Tb in patients with active tuberculosis (TB) in comparison with the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT).C-Tb and TST were randomly administered in a double-blinded fashion to one or the other forearm in 253 patients with active TB with or without HIV co-infection. QFT-GIT testing was performed prior to skin testing.Using a receiver operating characteristic curve-derived cut-point of 5 mm, C-Tb sensitivity was similar to QFT-GIT (73.9 (95% CI 67.8-79.3) versus 75.1 (95% CI 69.3-80.2)), and similar in HIV-infected and HIV-uninfected patients (76.7 (95% CI 69.0-83.3) versus 69.5 (95% CI 59.2-78.5)). However, sensitivity was significantly diminished in HIV-infected patients with CD4 counts <100 cells·mm(-3). C-Tb and QFT-GIT combined had significantly higher sensitivity than C-Tb alone (p<0.0001). C-Tb was safe with no significant adverse events. The 5 mm cut-point corresponded to that found in the previously published specificity study (TESEC-04).C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection. Sensitivity was reduced only in HIV-infected patients with severe immunosuppression. Further studies in different settings are required to validate the proposed 5 mm cut-point.

  5. Understanding social context on TB cases

    NASA Astrophysics Data System (ADS)

    Ariyanto, Y.; Wati, D. M.

    2017-01-01

    Tuberculosis (TB) nowadays still becomes one of the world’s deadliest communicable disease. More than half were in South-East Asia and Western Pacific Regions, including Indonesia. As developing country, Indonesia remains classic problems in overcoming TB, that is discontinuation on treatment. Most of discontinuation on treatment among TB patients are affected by diagnostic delay that caused by patient delay. These phenomena occur in many areas, rural to suburb, coastal to plantation, and so on, and they are related with social context among community that could be social capital for each community to deal with TB. Jember as one of county in East Java is known as plantation area. It also has a high prevalence of TB. This study focused on understanding about social context among community, especially on plantation area. This cross-sectional study involved in three districts of Jember, those are Tanggul, Pakusari, and Kalisat. The data were obtained directly from the TB patients, local community, and Primary Health Care (PHC) where the patients recorded. Spatial analysis and social network analysis (SNA) were applied to obtain health seeking behavior pattern among the TB patients coincide the community. Most of TB patients had already chosen health professionals to lead the treatment, although some of them remained to choose self-medication. Meanwhile, SNA showed that religious leader was considered as main part of countermeasures of TB. But they didn’t ever become central figures. So it can be concluded that there are other parts among community who can contribute due to combatting on TB.

  6. Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000–2012

    PubMed Central

    Delgado-Sánchez, Guadalupe; García-García, Lourdes; Castellanos-Joya, Martín; Cruz-Hervert, Pablo; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Hernández, Andrés; Ortega-Baeza, Victor Manuel; Montero-Campos, Rogelio; Sulca, José Antonio; Martínez-Olivares, Ma. de Lourdes; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; González-Roldán, Jesús Felipe; López-Gatell, Hugo; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; Jiménez-Corona, María Eugenia

    2015-01-01

    Background Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. Objective To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. Materials and Methods We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. Results In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p <0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p <0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11–1.61) p <0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. Conclusion Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure. PMID:26075393

  7. Waldenström's macroglobulinaemia in a bird breeder: a case history with pulmonary involvement and antibody activity of the monoclonal IgM to canary's droppings.

    PubMed Central

    James, J M; Brouet, J C; Orvoenfrija, E; Capron, F; Brechot, J; Danon, F; Diebold, J; Rochemaure, J; Zittoun, R

    1987-01-01

    A canary breeder with Waldenström's macroglobulinemia developed a pulmonary disease related to an interstitial infiltration by malignant B cells secreting a monoclonal IgM K. The serum monoclonal IgM was shown to possess an antibody activity to some canary's droppings antigen. This finding may help elucidate the natural course of lymphoid malignancies and the pathogenesis of rare visceral localizations. Images Fig. 1 Fig. 2 Fig. 3 PMID:3115646

  8. Clinical manifestations and outcomes of pulmonary aspergillosis: experience from Pakistan

    PubMed Central

    Iqbal, Nousheen; Irfan, Muhammad; Zubairi, Ali Bin Sarwar; Jabeen, Kauser; Awan, Safia; Khan, Javaid A

    2016-01-01

    Introduction Pulmonary aspergillosis has variable course of illness, severity and outcomes depending on underlying conditions. There is limited data available on the clinical manifestations and outcome of pulmonary aspergillosis from Pakistan. Methods To determine the clinical manifestations and outcome of pulmonary aspergillosis in a tertiary care hospital a retrospective study was conducted from 2004 to 2014 in patients admitted with pulmonary aspergillosis at the Aga Khan University Hospital Karachi, Pakistan. Results Of the 280 cases with provisional diagnosis of aspergillosis 69 met the inclusion criteria. The mean age was 45±15.7 years, 48 (69.6%) were men and 21 (30.4%) had diabetes mellitus (DM). The average length of hospital stay (LOS) was 10.61±9.08 days. Aspergillus fumigatus was the most common (42.0%), followed by Aspergillus flavus (28.9%). More than one-third of patients previously had tuberculosis (TB) (39.13%). The commonest pulmonary manifestation was chronic pulmonary aspergillosis (CPA) 47 (68.1%) followed by invasive pulmonary aspergillosis (IPA) 12 (17.4%) and subacute invasive aspergillosis (SAIA) 8 (11.6%). Surgical excision was performed in 28 patients (40.57%). Intensive care unit admission was required for 18 patients (26.08%). Case fatality rate was 14/69 (20.3%). DM, mean LOS and hypoxic respiratory failure were identified as independent risk factors of mortality on multivariate analysis. Conclusion A. fumigatus was the most frequent species found especially in patients with prior TB. CPA was the commonest pulmonary manifestation seen as post TB sequel. Diabetes, hypoxic respiratory failure and increased LOS were independent predictors of poor outcomes. Overall patients had good outcome with CPA compared with SAIA and IPA. PMID:28074136

  9. LUNG CANCER AND PULMONARY THROMBOEMBOLISM

    PubMed Central

    Cukic, Vesna; Ustamujic, Aida

    2015-01-01

    Introduction: Malignant diseases including lung cancer are the risk for development of pulmonary thromboembolism (PTE). Objective: To show the number of PTE in patients with lung cancer treated in Clinic for pulmonary diseases and TB “Podhrastovi” in three-year period: from 2012-2014. Material and methods: This is the retrospective study in which we present the number of various types of lung cancer treated in three-year period, number and per cent of PTE in different types of lung carcinoma, number and per cent of PTE of all diagnosed PTE in lung carcinoma according to the type of carcinoma. Results: In three-year period (from 2012 to 2014) 1609 patients with lung cancer were treated in Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Centre of Sarajevo University. 42 patients: 25 men middle –aged 64.4 years and 17 women middle- aged 66.7 or 2.61% of all patients with lung cancer had diagnosed PTE. That was the 16. 7% of all patients with PTE treated in Clinic “Podhrastovi “in that three-year period. Of all 42 patients with lung cancer and diagnosed PTE 3 patients (7.14%) had planocellular cancer, 4 patients (9.53%) had squamocellular cancer, 9 (21.43%) had adenocarcinoma, 1 (2.38%) had NSCLC, 3 (7.14 %) had microcellular cancer, 1 (2.38%) had neuroendocrine cancer, 2 (4.76%) had large cell-macrocellular and 19 (45.24%) had histological non-differentiated lung carcinoma. Conclusion: Malignant diseases, including lung cancer, are the risk factor for development of PTE. It is important to consider the including anticoagulant prophylaxis in these patients and so to slow down the course of diseases in these patients. PMID:26622205

  10. Hypoxia activates 15-PGDH and its metabolite 15-KETE to promote pulmonary artery endothelial cells proliferation via ERK1/2 signalling

    PubMed Central

    Ma, Cui; Liu, Yun; Wang, Yanyan; Zhang, Chen; Yao, Hongmin; Ma, Jun; Zhang, Lei; Zhang, Dandan; Shen, Tingting; Zhu, Daling

    2014-01-01

    BACKGROUND AND PURPOSE Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on the proliferation of pulmonary artery endothelial cells. EXPERIMENTAL APPROACH We used bromodeoxyuridine incorporation, cell-cycle analysis, immunohistochemistry and Western blot analysis to study the effects of hypoxia, induced 15-PGDH) activity and its product, 15-keto-6Z, 8Z, 11Z, 13E-eicosatetraenoic acid (15-KETE), on endothelial cell proliferation. Scratch-wound and tube formation assays were also used to study migration of endothelial cells. KEY RESULTS 15-KETE increased DNA synthesis and enhanced the transition from the G0/G1 phase to the S phase in hypoxia. Inhibition of 15-PGDH or siRNA for 15-PGDH reversed these effects. 15-KETE also activated the ERK1/2 signalling pathway. 15-KETE-induced cell migration and tube formation were reversed by blocking ERK1/2, but not the p38 MAPK pathway. CONCLUSIONS AND IMPLICATIONS Hypoxia-induced endothelial proliferation and migration, an important underlying mechanism contributing to hypoxic pulmonary vascular remodelling, appears to be mediated by 15-PGDH and 15-KETE, via the ERK1/2 signalling pathway. PMID:24467360

  11. The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis

    PubMed Central

    Cardona, Pere-Joan

    2015-01-01

    A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed. PMID:26136741

  12. Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation.

    PubMed

    Zhang, Yang; Liu, Gongjian; Dull, Randal O; Schwartz, David E; Hu, Guochang

    2014-07-15

    The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagy-related protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury.

  13. Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

    PubMed Central

    Efsen, Anne Marie W.; Schultze, Anna; Post, Frank A.; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F.; Losso, Marcelo H.; Toibaro, Javier; Skrahin, Aliaksandr; Miro, Jose M.; Caylà, Joan A.; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Podlekareva, Daria N.; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

    2015-01-01

    Objectives Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and Methods Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001). Conclusions In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART. PMID:26716686

  14. Spatial Alterations between CD4+ TFH, B and CD8+T cells during SIV infection: T/B cell homeostasis, activation and potential mechanism for viral escape

    PubMed Central

    Hong, Jung Joo; Amancha, Praveen K; Rogers, Kenneth; Ansari, Aftab A; Villinger, Francois

    2012-01-01

    HIV/SIV infections induce chronic immune activation with remodeling of lymphoid architecture and hypergammaglobulinemia, although the mechanisms leading to such symptoms remain to be fully elucidated. Moreover, lymph nodes have been highlighted as a predilection site for SIV escape in vivo. Following 20 rhesus macaques infected with SIVmac239, as they progress from pre to acute and chronic infection, we document for the first time the local dynamics T follicular helper (TFH) cells and B cells in situ. Progression of SIV infection was accompanied with increased numbers of well delineated follicles containing germinal centers (GCs) and TFH cells with a progressive increase in the density of PD-1 expression in lymph nodes. The rise in PD-1+ TFH cells was followed by a substantial accumulation of Ki67+ B cells within GCs. However, unlike in blood, major increases in the frequency of CD27+ memory B cells were observed in lymph nodes, indicating increased turnover of these cells, correlated with increases in total and SIV specific antibody levels. Of importance, compared to T cell zones, GCs seemed to exclude CD8+ T cells while harboring increasing numbers of CD4+ T cells, many of which are positive for SIVgag, providing an environment particularly beneficial for virus replication and reservoirs. Our data highlight for the first time important spatial interactions of GC cell subsets during SIV infection, the capacity of lymphoid tissues to maintain stable relative levels of circulating B cell subsets and a potential mechanism for viral reservoirs within GCs during SIV infection. PMID:22387550

  15. Soil Moisture Active Passive (SMAP) Project Algorithm Theoretical Basis Document SMAP L1B Radiometer Data Product: L1B_TB

    NASA Technical Reports Server (NTRS)

    Piepmeier, Jeffrey; Mohammed, Priscilla; De Amici, Giovanni; Kim, Edward; Peng, Jinzheng; Ruf, Christopher; Hanna, Maher; Yueh, Simon; Entekhabi, Dara

    2016-01-01

    The purpose of the Soil Moisture Active Passive (SMAP) radiometer calibration algorithm is to convert Level 0 (L0) radiometer digital counts data into calibrated estimates of brightness temperatures referenced to the Earth's surface within the main beam. The algorithm theory in most respects is similar to what has been developed and implemented for decades for other satellite radiometers; however, SMAP includes two key features heretofore absent from most satellite borne radiometers: radio frequency interference (RFI) detection and mitigation, and measurement of the third and fourth Stokes parameters using digital correlation. The purpose of this document is to describe the SMAP radiometer and forward model, explain the SMAP calibration algorithm, including approximations, errors, and biases, provide all necessary equations for implementing the calibration algorithm and detail the RFI detection and mitigation process. Section 2 provides a summary of algorithm objectives and driving requirements. Section 3 is a description of the instrument and Section 4 covers the forward models, upon which the algorithm is based. Section 5 gives the retrieval algorithm and theory. Section 6 describes the orbit simulator, which implements the forward model and is the key for deriving antenna pattern correction coefficients and testing the overall algorithm.

  16. The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

    PubMed Central

    Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

  17. The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

    PubMed

    Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

  18. Multidrug and extensively drug-resistant TB (M/XDR-TB): problems and solutions.

    PubMed

    Prasad, Rajendra

    2010-10-01

    Multi Drug Resistant Tuberculosis (MDR-TB) and Extensively Drug Resistant Tuberculosis (XDR-TB) are posing a threat to the control of tuberculosis. The first WHO-IUATLD antituberculosis drug resistance surveillance carried out in 1994 in 35 countries reported the median prevalence of primary and acquired multi drug resistance as 1.4% and 13% respectively. Subsequently, second, third and fourth WHO-IUATLD global drug resistance surveillances were carried out in 1996-99, 1999-2002 and 2002-2007 respectively. Based on drug resistance information from 114 countries, the proportion of MDR-TB among all cases was estimated for countries with no survey information. It was estimated that 4,89,139 cases of MDR-TB emerged in 2006. China and India carry approximately 50% of the global burden. 35 countries and two Special Administrative Regions (SARs) reported data on XDR-TB for the first time in 2006. Multidrug and extensively drug-resistant TB 2010 Global report on Surveillance and response estimated that 4,40,000 cases of MDR-TB emerged globally in 2008 and caused an estimated 1,50,000 deaths. 5.4% of MDR-TB cases were found to have XDR-TB. To date, a cumulative total of 58 countries have confirmed at least one case of XDR-TB. M/XDR-TB is a man-made problem and its emergence can be prevented by prompt diagnosis and effective use of first line drugs in every new patient. The DOTS Plus proposed by WHO highlights the comprehensive management strategy to control MDR-TB. Laboratory services for adequate and timely diagnosis of M/XDR-TB must be strengthened and programmatic management of M/XDR-TB must be scaled up as per target set by global plan. Proper use of second-line drugs must be ensured to cure existing MDR-TB, to reduce its transmission and to prevent XDR-TB. Sound infection control measures to avoid further transmission of M/XDR-TB and research towards development of new diagnostics, drugs and vaccines should be promoted to control M/XDR-TB.

  19. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in Hiv-positive adults

    PubMed Central

    Shah, Maunank; Hanrahan, Colleen; Wang, Zhuo Yu; Dendukuri, Nandini; Lawn, Stephen D; Denkinger, Claudia M; Steingart, Karen R

    2016-01-01

    -positive individuals with low CD4 counts who are seriously ill, LF-LAM may help with the diagnosis of TB. PLAIN LANGUAGE SUMMARY The lateral flow urine lipoarabinomannan (LF-LAM) test for diagnosis of tuberculosis in people living with human immunodeficiency virus (HIV) Background Tuberculosis (TB) is a common cause of death in people with human immunodeficiency virus (HIV) infection, but diagnosis is difficult, and depends on testing for TB in the sputum and other sites, which may take weeks to give results. A rapid and accurate point-of-care test could reduce delays in diagnosis, allow treatment to start promptly, and improve linkage between diagnosis and treatment. Test evaluated by this review The lateral flow urine lipoarabinomannan assay (LF-LAM, Alere Determine™ TB LAM Ag, Alere Inc, Waltham, MA, USA) is a commercially available point-of-care test for active TB (pulmonary and extrapulmonary TB). The test detects lipoarabinomannan (LAM), a component of the bacterial cell walls, which is present in some people with active TB. The test is performed by placing urine on one end of a test strip, with results appearing as a line (that is, a band) on the strip if TB is present. The test is simple, requires no special equipment, and shows results in 25 minutes. During the period we conducted the review, the manufacturer issued new recommendations for defining a positive test. We collected data based on both the original and the new recommendations Objectives We aimed to see how accurately LF-LAM diagnosed TB in people living with HIV with TB symptoms, and how accurately LF-LAM diagnosed TB in people living with HIV being screened for TB whether or not they had TB symptoms. Main results We examined evidence up to 5 February 2015 and included 12 studies: six studies evaluated LF-LAM for TB diagnosis and six studies evaluated the test for TB screening. All studies were conducted in low- or middle-income countries. Quality of the evidence We assessed quality by describing how participants

  20. Predictors and Timing of ATT Initiation among HIV-TB Patients at ART Centers of Karnataka, India: Two Year Follow-Up

    PubMed Central

    Shastri, Suresh; Nagaraja, Sharath Burugina; Tripathy, Jaya Prasad; Satyanarayana, Srinath; Rewari, Bharat Bhushan

    2015-01-01

    Background In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states. Objectives To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients. Methods Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011. Results A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome. Conclusions The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment. PMID:26394397

  1. Association between peripheral muscle strength, exercise performance, and physical activity in daily life in patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    2014-01-01

    Background Resistance training of peripheral muscles has been recommended in order to increase muscle strength in patients with Chronic Obstructive Pulmonary Disease (COPD). However, whether peripheral muscle strength is associated with exercise performance (EP) and physical activity in daily life (PADL) in these patients needs to be investigated. The aim of this study is to evaluate whether strength of the quadriceps muscle (QS) is associated with EP and daily PADL in patients with COPD. Methods We studied patients with COPD (GOLD A-D) and measured maximal isometric strength of the left QS. PADL was measured for 7 days with a SenseWear-Pro® accelerometer. EP was quantified by the 6-minute walk distance (6MWD), the number of stands in the Sit-to-Stand Test (STST), and the handgrip-strength. Univariate and multivariate analyses were used to examine possible associations between QS, PADL and EP. Results In 27 patients with COPD with a mean (SD) FEV1 of 37.6 (17.6)% predicted, QS was associated with 6MWD, STST, and handgrip-strength but not with PADL. Multiple linear regression analyses showed that QS was independently associated with the 6MWD (β = 0.42, 95% CI 0.09 to 0.84, p = 0.019), STST (β = 0.50, 95% CI 0.11 to 0.86, p = 0.014) and with handgrip-strength (β = 0.45, 95% CI 0.05 to 0.84, p = 0.038). Conclusions Peripheral muscle strength may be associated with exercise performance but not with physical activity in daily life. This may be due to the fact that EP tests evaluate patients’ true abilities while PADL accelerometers may not. PMID:25013723

  2. Pulmonary tuberculosis - An emerging risk factor for venous thromboembolism: A case series and review of literature

    PubMed Central

    Gupta, Amitesh; Mrigpuri, Parul; Faye, Abhishek; Bandyopadhyay, Debdutta; Singla, Rupak

    2017-01-01

    One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%–50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%–3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases. PMID:28144063

  3. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    SciTech Connect

    Kalayarasan, Srinivasan Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam

    2013-09-01

    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

  4. Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

    PubMed Central

    2013-01-01

    Background A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras. PMID:23497342

  5. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response

    SciTech Connect

    Zheng, Yi; Tao, Shasha; Lian, Fangru; Chau, Binh T.; Chen, Jie; Sun, Guifan; Fang, Deyu; Lantz, R. Clark; Zhang, Donna D.

    2012-12-15

    Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure. -- Highlights: ► Exposed to arsenic particles and/or SF have elevated Nrf2 and its target genes. ► Sulforaphane prevents pathological alterations, oxidative damage and cell death. ► Sulforaphane alleviates infiltration of inflammatory cells into the lungs. ► Sulforaphane suppresses arsenic-induced proinflammatory cytokine production.

  6. Enhanced luminescence of Tb3 + due to efficient energy transfer from Ce3 + in a nanocrystalline Lu2Si2O7 host lattice

    NASA Astrophysics Data System (ADS)

    Sokolnicki, J.

    2010-07-01

    Nanocrystalline lutetium pyrosilicate Lu2Si2O7 (LPS) doped with Tb3 + (LPS:Tb) or Ce3 + /Tb3 + (LPS:Ce, Tb) was obtained at 1250 °C by the reaction of nanostructured Lu2O3 and colloidal SiO2. X-ray diffraction analysis confirmed the crystallization of a single phase of LPS at the indicated temperature. Different concentrations of active ions allowed us to study the influence of Ce3 + co-doping on Tb3 + emission. Tb3 + -doped LPS yields both the blue emission ^{5}\\mathrm {D}_{3} \\to {}^{7}\\mathrm {F}_{J} (J = 3, 4, 5, 6) and the green emission ^{5}\\mathrm {D}_{4} \\to {}^{7}\\mathrm {F}_{J} (J = 3, 4, 5, 6) of Tb3 + . The green emission of Tb3 + is enhanced remarkably in both the cathodoluminescence and photoluminescence spectra because of energy transfer from Ce3 + to Tb3 + ions, both of which are present in the host lattice. Based on the optical luminescence and luminescence excitation spectra, the optimal Tb3 + doping level for maximum light output was established to be 9 mol% and the highest enhancement of Tb3 + luminescence by Ce3 + co-doping was detected using a 1:3 ratio of Ce3 + /Tb3 + concentration. Two different crystallographic sites of Tb3 + in the LPS lattice were detected in the luminescence and excitation spectra of samples with higher Tb3 + concentrations (6-9 mol%). The single-exponential decay profile of 5D4 emission for the less concentrated samples and the double-exponential decay for the higher doping level are in agreement with this observation. Calculation of colour coordinates shows that LPS:Ce(0.25%)Tb(3%) emits white light.

  7. Pulmonary Vascular Impedance in Chronic Pulmonary Hypertension.

    DTIC Science & Technology

    PULMONARY HYPERTENSION , *PULMONARY BLOOD CIRCULATION, BLOOD CIRCULATION, LUNG, PATHOLOGY, VASCULAR DISEASES, ARTERIES, OBSTRUCTION(PHYSIOLOGY...EMBOLISM, HISTOLOGY, DOGS, LABORATORY ANIMALS, BLOOD PRESSURE , EXPERIMENTAL DATA