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Sample records for active pulmonary tb

  1. An African woman with pulmonary cavities: TB or not TB?

    PubMed

    Delsing, C E; Ruesen, C; Boeree, M J; van Damme, P A; Kuipers, S; van Crevel, R

    2014-10-01

    Cavitary lung lesions in patients from developing countries are mostly caused by tuberculosis (TB). However, when TB cannot be confirmed, a primary lung abscess caused by anaerobic bacteria from the mouth should be considered, especially in patients with poor dentition. We present a case of a Sudanese woman with a cavitary lung lesion and severe gingivitis. Bulleidia extructa was isolated as a single pathogen from the pulmonary cavity. PMID:25387555

  2. Diagnostic Utility of QuantiFERON-TB Gold (QFT-G) in Active Pulmonary Tuberculosis

    PubMed Central

    Anwar, Ahmed; Hamdan, AL-Jahdali; Salim, Baharoon; Yosra, Ali; Hani, Mohamed; Abdullah, AL-Harbi

    2015-01-01

    Background: The utility of QuantiFERON-TB Gold In-Tube (QFT-G) test in the diagnosis of tuberculosis disease has been validated in high and low tuberculosis-prevalent (TB) countries. Aim: The aim of this study is to assess the performance of the QFT-G test in the diagnosis of tuberculosis disease among tuberculosis patients in an intermediate prevalent country. Setting and Design: A retrospective study at the King Abdulaziz Medical City-Riyadh (KAMC-R) Materials and Methods: We retrospectively reviewed all the patients with a diagnosis of pneumonia, including tuberculosis, admitted to KAMC-R between 1 January 2009 and 31 December 2013. We included only patients with an available result of the QFT-G test. A total of 142 tuberculosis cases and 226 pneumonia cases were studied, to assess the utility of the QFT-G test in diagnosing tuberculosis cases. Results: Among the tuberculosis (n = 142) cases, the QFT-G tested positive in 68.3%, negative in 23.2%, and indeterminate in 12 cases (8.5%). Of the 226 pneumonia cases, the QFT-G tested positive in only 20.4%, while a majority of 66.4% tested negative, with 30 cases (13.3%) being indeterminate. When we excluded 42 patients with indeterminate results, the QFT-G test achieved a sensitivity of 74.6% [95% CI: 66.09 to 81.65%] and specificity of 76.53 % [95% CI: 69.85 to 82.15%] in the diagnosis of tuberculosis cases. Conclusions: This study concludes that the QFT-G test is a useful tool for detecting tuberculosis disease when used as an adjunct tool for the diagnosis of active TB cases. It certainly cannot be used solely and indiscriminately, separate from other clinical and radiological information, in the diagnosis of active tuberculosis cases. PMID:26392718

  3. T-SPOT.TB in Detection of Active Tuberculosis During Pregnancy: A Retrospective Study in China

    PubMed Central

    Chen, Qiaopei; Guo, Xuxiao; Wang, Xinfeng; Wang, Maoshui

    2016-01-01

    Background Interferon-gamma release assays have not been validated in active TB among pregnant women. Therefore, the objective of this retrospective study was to estimate the diagnostic value of T-SPOT.TB in active TB among pregnant women. Material/Methods Between May 2012 and May 2015, 26 consecutive pregnant women with suspected TB were enrolled in our study. The clinicopathological characteristics and T-SPOT.TB results were reviewed and analyzed. Results Pregnant patients were divided into a TB group (n=21) and a Non-TB group (n=5). In the TB group, 5 patients had pulmonary TB, 5 had pulmonary TB+ extrapulmonary TB, and 11 had exclusively extrapulmonary TB. The most common site of extrapulmonary TB was pleural (n=11). Statistical analysis showed that the lymphocyte count in the TB group was lower than in the Non-TB group (P<0.05). For detection of active TB during pregnancy, T-SPOT.TB had a high sensitivity of 100.0% (84.5%–100.0%) and a specificity of 80.0% (37.6–96.4%). Conclusions T-SPOT.TB shows good performance in detection of active tuberculosis during pregnancy. Interferon gamma release assay for TB screening of pregnant women is recommended in clinical practice because it may be a more appropriate diagnostic tool than the tuberculin skin test. PMID:26732770

  4. Difference Between Latent TB Infection and Active TB Disease

    MedlinePlus

    ... ray, or positive sputum smear or culture • • Has active TB bacteria in his/her body • • Usually feels sick and may have symptoms such as coughing, fever, and weight loss • • May spread TB bacteria to others • • Needs treatment to treat ...

  5. Combination of Cytokine Responses Indicative of Latent TB and Active TB in Malawian Adults

    PubMed Central

    Hur, Yun-Gyoung; Gorak-Stolinska, Patricia; Ben-Smith, Anne; Lalor, Maeve K.; Chaguluka, Steven; Dacombe, Russell; Doherty, T. Mark; Ottenhoff, Tom H.; Dockrell, Hazel M.; Crampin, Amelia C.

    2013-01-01

    Background An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens may enable differentiation of latent TB from active disease. Methods Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with M. tuberculosis-derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested. Results Spouses with positive IFN-γ responses to M. tuberculosis ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to M. tuberculosis-derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses. Conclusions CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose M. tuberculosis infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB. PMID:24260295

  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. Socio-Demographic Predictors and Distribution of Pulmonary Tuberculosis (TB) in Xinjiang, China: A Spatial Analysis

    PubMed Central

    Wubuli, Atikaimu; Xue, Feng; Jiang, Daobin; Yao, Xuemei; Upur, Halmurat; Wushouer, Qimanguli

    2015-01-01

    Objectives Xinjiang is one of the high TB burden provinces of China. A spatial analysis was conducted using geographical information system (GIS) technology to improve the understanding of geographic variation of the pulmonary TB occurrence in Xinjiang, its predictors, and to search for targeted interventions. Methods Numbers of reported pulmonary TB cases were collected at county/district level from TB surveillance system database. Population data were extracted from Xinjiang Statistical Yearbook (2006~2014). Spatial autocorrelation (or dependency) was assessed using global Moran’s I statistic. Anselin’s local Moran’s I and local Getis-Ord statistics were used to detect local spatial clusters. Ordinary least squares (OLS) regression, spatial lag model (SLM) and geographically-weighted regression (GWR) models were used to explore the socio-demographic predictors of pulmonary TB incidence from global and local perspectives. SPSS17.0, ArcGIS10.2.2, and GeoDA software were used for data analysis. Results Incidence of sputum smear positive (SS+) TB and new SS+TB showed a declining trend from 2005 to 2013. Pulmonary TB incidence showed a declining trend from 2005 to 2010 and a rising trend since 2011 mainly caused by the rising trend of sputum smear negative (SS-) TB incidence (p<0.0001). Spatial autocorrelation analysis showed the presence of positive spatial autocorrelation for pulmonary TB incidence, SS+TB incidence and SS-TB incidence from 2005 to 2013 (P <0.0001). The Anselin’s Local Moran’s I identified the “hotspots” which were consistently located in the southwest regions composed of 20 to 28 districts, and the “coldspots” which were consistently located in the north central regions consisting of 21 to 27 districts. Analysis with the Getis-Ord Gi* statistic expanded the scope of “hotspots” and “coldspots” with different intensity; 30 county/districts clustered as “hotspots”, while 47 county/districts clustered as

  8. 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. PMID:21251883

  9. Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis.

    PubMed

    Souza de Lima, D; Ogusku, M M; Sadahiro, A; Pontillo, A

    2016-07-01

    Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection. PMID:27101784

  10. TB-SA antibody test for diagnosis and monitoring treatment outcome of sputum smear negative pulmonary tuberculosis patients.

    PubMed

    Li, Xinxu; Xu, Hancheng; Jiang, Shiwen; Jing, Kuanhe; Wang, Li; Liu, Xiaoqiu; Li, Weibin; Zhang, Hui; Wang, Lixia

    2011-09-01

    The objectives of this study were to evaluate the suitability of the TB-SA antibody test to diagnose tuberculosis in sputum smear negative (SS-) pulmonary tuberculosis (TB) patients and its applicability for monitoring treatment outcomes in these patients. This study was conducted in three counties/districts in Chongqing Municipality, Liaoning Province, China between June 2005 and June 2007. A total of 432 SS suspected pulmonary TB patients were recruited and their blood was collected prior to treatment, at the end of 1 month of treatment, 2 months of treatment and 6 months of treatment (E6MT). The serum samples were analyzed with a TB-SA antibody test kit. Of the 432 SS suspected pulmonary TB patients, serum samples were obtained at all time points in 316 patients and analyzed. The 316 patients were divided into three groups according to sputum smear and sputum culture results and the chest X-ray results before treatment and at E6MT. Ten point four percent were SS-/culture positive (C+), 73.1% were SS-/culture negative (C-) with X-rays abnormalities, and 16.5% were SS-/C- without X-rays abnormalities. The positive rates for TB-SA antibody in the three groups were 57.6, 44.6 and 44.2%, respectively, before treatment, and 18.2, 19.1 and 26.9%, respectively, at E6MT. There was a significant decrease in TB-SA antibody positivity with treatment for all 3 groups. The TB-SA antibody test may be a useful adjunct to diagnose tuberculosis in SS- pulmonary TB patients, and may be useful for monitoring treatment outcomes of SS- pulmonary TB patients. PMID:22299440

  11. 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

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

    PubMed Central

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

    2015-01-01

    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 multi-parametric 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. PMID:25956974

  13. Rapid Screening of MDR-TB in Cases of Extra Pulmonary Tuberculosis Using Geno Type MTBDRplus

    PubMed Central

    Kumari, Richa; Tripathi, Rajneesh; Pandey, Alok Prakash; Banerjee, Tuhina; Sinha, Pallavi; Anupurba, Shampa

    2016-01-01

    Background Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes. Methods A total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ) media. Phenotypic drug susceptibility testing (DST) was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method. Results Of 510 specimens cultured, the total culture positivity obtained was 11.8% (60) encompassing 54 (10.6%) Mycobacterium tuberculosis and 6 (1.2%) non-tubercular mycobacteria (NTM). DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB) in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours. Conclusion The problem of MDR in extra pulmonary tuberculosis (EPTB) cannot be overlooked and

  14. A comparison between passive and active case finding in TB control in the Arkhangelsk region

    PubMed Central

    Kuznetsov, Vladimir N.; Grjibovski, Andrej M.; Mariandyshev, Andrey O.; Johansson, Eva; Bjune, Gunnar A.

    2014-01-01

    Background In Russia, active case finding (ACF) for certain population groups has been practiced uninterruptedly for many decades, but no studies comparing ACF and passive case finding (PCF) approaches in Russia have been published. Objective The aim of this study was to describe the main differences in symptoms and diagnostic delay between patients who come to TB services through PCF and ACF strategies. Methods A cross-sectional study was conducted among 453 new pulmonary tuberculosis (PTB) patients, who met criteria of TB diagnostic delay in Arkhangelsk. Results ACF patients used self-treatment more often than PCF patients (90.1% vs. 24.6%) and 36.3% of them were alcohol abusers (as opposed to only 26.2% of PCF patients). The median patient delay (PD) in PCF was 4 weeks, IQR (1–8 weeks), and less than 1 week in ACF. Twenty-three per cent of the PCF patients were seen by a medical provider within the first week of their illness onset. Conclusion Patients diagnosed through ACF tended to under-report their TB symptoms and showed low attention to their own health. However, ACF allowed for discovering TB patients earlier than PCF, and this was also the case for alcohol abusing patients. PCF systems should be supplemented with ACF strategies. PMID:24563859

  15. Coincident Helminth Infection Modulates Systemic Inflammation and Immune Activation in Active Pulmonary Tuberculosis

    PubMed Central

    George, Parakkal Jovvian; Kumar, Nathella Pavan; Sridhar, Rathinam; Hanna, Luke E.; Nair, Dina; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

    2014-01-01

    Background Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity) in TB is not known. Methodology We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB) with co-incidental Strongyloides stercoralis (Ss) infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB) with or without Ss infection. Principal Findings Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection. Conclusions Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease. PMID:25375117

  16. Interleukin 17-Producing γδ T Cells Increased in Patients with Active Pulmonary Tuberculosis

    PubMed Central

    Peng, Meiyu; Wang, Zhaohua; Yao, Chunyan; Jiang, Lina; Jin, Qili; Wang, Jing; Li, Baiqing

    2008-01-01

    Although it has been known that γδ T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis (M. tb), the mechanisms by which the γδ T cells participate in the innate and/or acquired immunity to tuberculosis (TB) have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors (HD) were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of γδ T cells in IL-17-producing cells (59.2%) and IL-17-producing cells in γδ T cells (19.4%) in peripheral blood were markedly increased in TB patients when compared to those in HD (43.9% and 7.7%, respectively). In addition, the proportions of IFN-γ-producing γδ T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen (M. tb-HAg) in vitro, fewer IL-17-producing γδ T cells were generated from HD and TB patients, whereas IFN-γ-producing γδ T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17-producing γδ T cells were main source of IL-17 in mouse model of BCG infection, suggesting that γδ T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification. PMID:18582402

  17. 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

  18. 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

  19. Pulmonary Myeloperoxidase Activity

    PubMed Central

    Ozment, Tammy Regena

    2016-01-01

    Neutrophils are considered one of the first responders of the innate immune response. Their primary activities are to migrate to sites of infection by chemotaxis and trans-migration across the endothelium (Gaines et al., 2005). Once at the site of infection, they phagocytize microbes and kill them. Critical to the neutrophil's ability to kill microbes are the multiple degradative enzymes contained within granules. The activity of these enzymes is non-specific, and therefore, neutrophils also contribute to tissue damage at the site of infection (Gaines and Berliner, 2005). Measurement of neutrophil infiltration into tissues is one way to gauge the severity of infection, inflammation, and tissue damage (Ayala et al., 2002). Myeloperoxidase is found in the primary granules of neutrophils and is an effective measure of neutrophil infiltration into tissues (Gaines and Berliner, 2005).

  20. Pulmonary tuberculosis: clinical features and patient management.

    PubMed

    Gough, Andrea; Kaufman, Gerri

    Pulmonary tuberculosis (TB) is a common infectious disease and a major cause of illness and death throughout the world, particularly in developing countries. This article explores the difference between latent TB infection and active TB disease, and discusses the pharmacological management of TB and issues around adherence to medication. Although TB is usually managed by specialist teams it is essential that all practitioners have an understanding of the signs and symptoms of the disease to ensure early referral and accurate diagnosis. PMID:21888103

  1. Evaluation of the Rapid Scale-up of Collaborative TB/HIV Activities in TB Facilities in Rwanda, 2005-2009

    PubMed Central

    2011-01-01

    Background In 2005, Rwanda drafted a national TB/HIV policy and began scaling-up collaborative TB/HIV activities. Prior to the scale-up, we evaluated existing TB/HIV practices, possible barriers to policy and programmatic implementation, and patient treatment outcomes. We then used our evaluation data as a baseline for evaluating the national scale-up of collaborative TB/HIV activities from 2005 through 2009. Methods Our baseline evaluation included a cross-sectional evaluation of 23/161 TB clinics. We conducted structured interviews with patients and clinic staff and reviewed TB registers and patient records to assess HIV testing practices, provision of HIV care and treatment for people with TB that tested positive for HIV, and patients' TB treatment outcomes. Following our baseline evaluation, we used nationally representative TB/HIV surveillance data to monitor the scale-up of collaborative TB/HIV activities Results Of 207 patients interviewed, 76% were offered HIV testing, 99% accepted, and 49% reported positive test results. Of 40 staff interviewed, 68% reported offering HIV testing to >50% of patients. From 2005-2009, scaled-up TB/HIV activities resulted in increased HIV testing of patients with TB (69% to 97%) and provision of cotrimoxazole (15% to 92%) and antiretroviral therapy (13% to 49%) for patients with TB disease and HIV infection (TB/HIV). The risk of death among patients with TB/HIV relative to patients with TB not infected with HIV declined from 2005 (RR = 6.1, 95%CI 2.6, 14.0) to 2007 (RR = 1.8, 95%CI 1.68, 1.94). Conclusions Our baseline evaluation highlighted that staff and patients were receptive to HIV testing. However, expanded access to testing, care, and treatment was needed based on the proportion of patients with TB having unknown HIV status and the high rate of HIV infection and poorer TB treatment outcomes for patients with TB/HIV. Following our evaluation, scale-up of TB/HIV services resulted in almost all patients with TB knowing

  2. Role of QuantiFERON-TB Gold antigen-specific IL-1β in diagnosis of active tuberculosis.

    PubMed

    Prabhavathi, Maddineni; Kabeer, Basirudeen Syed Ahamed; Deenadayalan, Anbarasu; Raja, Alamelu

    2015-10-01

    The main objective of the study was to evaluate whether in vitro QuantiFERON-TB Gold In-Tube (QFT-GIT) assay antigen-specific IL-1β, TNF-α, IL-2, IL-6, IL-8 and IL-12 (p40) production is associated with active TB. In a cohort of 77 pulmonary TB patients (PTB), 67 healthy household contacts (HHC) and 83 healthy control subjects (HCS), the antigen-specific cytokines levels were determined in supernatants generated from QFT-GIT tubes. Antigen-specific IL-1β levels were significantly higher in PTB than HHC and HCS. At a fixed cutoff point (1,108 pg/ml), IL-1β showed positivity of 62.33% in PTB, 22.38% in HHC and 22.89% in HCS. Moreover, antigen-specific IL-1β assay can differentiate PTB and HHC (believed to be latently infected) (p < 0.0001). Like IL-1β, significantly higher levels of antigen-specific TNF-α were associated with PTB and displayed 43.63% positivity in PTB. The antigen-specific IL-2 levels were associated both with PTB (54.54%) and HHC (48.14%). Other cytokines levels did not differ among the groups. Our results suggest that antigen-specific IL-1β can be used as a biomarker for active TB diagnosis as well as for differential diagnosis of PTB and LTBI. PMID:25504009

  3. 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

  4. Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

    PubMed

    Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

    2016-01-01

    India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. PMID:27235937

  5. Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania

    PubMed Central

    Chigutsa, Emmanuel; Faurholt-Jepsen, Daniel; PrayGod, George; Range, Nyagosya; Castel, Sandra; Wiesner, Lubbe; Hagen, Christian Munch; Christiansen, Michael; Changalucha, John; McIlleron, Helen; Friis, Henrik; Andersen, Aase Bengaard

    2015-01-01

    Exposure to lower-than-therapeutic levels of anti-tuberculosis drugs is likely to cause selection of resistant strains of Mycobacterium tuberculosis and treatment failure. The first-line anti-tuberculosis (TB) regimen consists of rifampicin, isoniazid, pyrazinamide, and ethambutol, and correct management reduces risk of TB relapse and development of drug resistance. In this study we aimed to investigate the effect of standard of care plus nutritional supplementation versus standard care on the pharmacokinetics of isoniazid, pyrazinamide and ethambutol among sputum smear positive TB patients with and without HIV. In a clinical trial in 100 Tanzanian TB patients, with or without HIV infection, drug concentrations were determined at 1 week and 2 months post initiation of anti-TB medication. Data was analysed using population pharmacokinetic modelling. The effect of body size was described using allometric scaling, and the effects of nutritional supplementation, HIV, age, sex, CD4+ count, weight-adjusted dose, NAT2 genotype, and time on TB treatment were investigated. The kinetics of all drugs was well characterised using first-order elimination and transit compartment absorption, with isoniazid and ethambutol described by two-compartment disposition models, and pyrazinamide by a one-compartment model. Patients with a slow NAT2 genotype had higher isoniazid exposure and a lower estimate of oral clearance (15.5 L/h) than rapid/intermediate NAT2 genotype (26.1 L/h). Pyrazinamide clearance had an estimated typical value of 3.32 L/h, and it was found to increase with time on treatment, with a 16.3% increase after the first 2 months of anti-TB treatment. The typical clearance of ethambutol was estimated to be 40.7 L/h, and was found to decrease with age, at a rate of 1.41% per year. Neither HIV status nor nutritional supplementations were found to affect the pharmacokinetics of these drugs in our cohort of patients. PMID:26501782

  6. The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

    PubMed

    Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

    2016-01-01

    Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. PMID:26631832

  7. IL-10 Dependent Suppression of Type 1, Type 2 and Type 17 Cytokines in Active Pulmonary Tuberculosis

    PubMed Central

    Kumar, Nathella Pavan; Gopinath, Venugopal; Sridhar, Rathinam; Hanna, Luke E.; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

    2013-01-01

    Background Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB), their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL) and latent tuberculosis (LTB) have not been well studied. Aim and Methods To identify cytokine responses associated with pulmonary tuberculosis (TB), TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA. Results PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2); Type 2 (IL-4) and Type 17 (IL-17A and IL-17F) cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially) the suppression of cytokine responses in PTB. Conclusion Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB. PMID:23544075

  8. Microwave synthesis and photocatalytic activity of Tb(3+) doped BiVO4 microcrystals.

    PubMed

    Wang, Ying; Liu, Fuyang; Hua, Yingjie; Wang, Chongtai; Zhao, Xudong; Liu, Xiaoyang; Li, Hongdong

    2016-12-01

    Tb(3+) doped BiVO4 has been successfully synthesized by a simple microwave-assisted hydrothermal method at 140°C for 30min. The structure, morphology and optical property of the Tb(3+) doped BiVO4 products have been systematically investigated. This study indicates that the incorporation of Tb(3+) could induce the conversion of structure from monoclinic to tetragonal for BiVO4. Furthermore, the as-obtained Tb(3+) doped BiVO4 samples showed an obvious morphological change: the hollow square rod-like BiVO4 crystal gradually changed to spindle-like crystal. The Tb(3+) doped BiVO4 products exhibited extraordinary photocatalytic activity for Methylene Blue (MB) degradation under visible light irradiation. The doped BiVO4 at a molar ratio of 2at% (Tb and Bi) with a mixture of monoclinic and tetragonal phases showed and prominent photocatalytic degradation rate, which reached 99.9% in 120min. The results suggest that the differences in the photocatalytic activity of these BiVO4 crystals with different Tb(3+) doping concentrations can be attributed to the change of crystalline phases, and the coexistence of the monoclinic/tetragonal phases in BiVO4 products, which improve the efficient charge separation and transportation. PMID:27565962

  9. NF-κB Repressing Factor Inhibits Chemokine Synthesis by Peripheral Blood Mononuclear Cells and Alveolar Macrophages in Active Pulmonary Tuberculosis

    PubMed Central

    Huang, Kuo-Hsiung; Wang, Chun-Hua; Lee, Kang-Yun; Lin, Shu-Min

    2013-01-01

    NF-κB repressing factor (NRF) is a transcriptional silencer implicated in the basal silencing of specific NF-κB targeting genes, including iNOS, IFN-β and IL-8/CXCL8. IP-10/CXCL10 and IL-8/CXCL8 are involved in neutrophil and lymphocyte recruitment against M. tuberculosis (MTb) and disease progression of pulmonary tuberculosis (TB). Alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) were used to study the regulatory role of NRF in pulmonary TB. AM and PBMC were purified from 19 TB patients and 15 normal subjects. To study the underlying mechanism, PBMC were exposed to heated TB bacilli. The regulation role of NRF in IP-10/CXCL10 and IL-8/CXCL8 was determined by NRF knock-down or over-expression. NRF binding capabilities in promoter sites were measured by chromatin immunoprecipitation (ChIP) assay. The levels of IP-10/CXCL10, IL-8/CXCL8 and NRF were significantly higher in AM and PBMC in patients with active TB. NRF played an inhibitory role in IP-10/CXCL10 and IL-8/CXCL8 inductions. We delineate the role of NRF in pulmonary TB, which inhibits the expressions of IP-10/CXCL10 and IL-8/CXCL8 in AM and PBMC of patients with high bacterial load. NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high. PMID:24223729

  10. A prospective cohort study of latent tuberculosis in adult close contacts of active pulmonary tuberculosis patients in Korea

    PubMed Central

    Park, Sun Hyo; Lee, Seung Jun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Hee Jin; Menzies, Dick

    2016-01-01

    Background/Aims: The objective of this prospective study was to evaluate the diagnosis and treatment of latent tuberculosis infection (LTBI) in adult close contacts of active pulmonary tuberculosis (TB) patients in Korea. Methods: Adult close contacts of active pulmonary TB patients were recruited at a regional tertiary hospital in Korea. The participants were tested for LTBI using the tuberculin skin test (TST) and/or QuantiFERON-TB Gold (QFT-G) test. LTBI patients, who consented to treatment, were randomly assigned to receive isoniazid for 9 months (9INH) or rifampin for 4 months (4RIF). Results: We examined 189 adult close contacts (> 18 years) of 107 active pulmonary TB patients. The TST and QFT-G were positive (≥ 10 mm) in 75/183 (39.7%) and 45/118 (38.1%) tested participants, respectively. Among 88 TST or QFT-G positive LTBI participants, 45 participants were randomly assigned to receive 4RIF (n = 21) or 9INH (n = 24), respectively. The average treatment duration for the 4RIF and 9INH groups was 3.3 ± 1.3 and 6.1 ± 2.7 months, respectively. Treatment was completed in 25 participants (4RIF, n = 16; 9INH, n = 9). LTBI participants who accepted treatment were more likely to be women and have more cavitary lesions on the chest radiographs of index cases and positive TST and QFT-G results compared to those who refused treatment. Conclusions: About 40% of adult close contacts of active pulmonary TB patients had LTBI; about 50% of these LTBI participants agreed to treatment. PMID:27052266

  11. The Mycobacterium tuberculosis PPE protein Rv1168c induces stronger B cell response than Rv0256c in active TB patients.

    PubMed

    Abraham, Philip Raj; Udgata, Atul; Latha, Gaddam Suman; Mukhopadhyay, Sangita

    2016-06-01

    Tuberculosis (TB) caused by Mycobacterium tuberculosis is a serious global health problem and is responsible for millions of deaths every year. For effective control of this dreadful disease, it is necessary to diagnose TB cases at the initial stages of infection. The serodiagnosis of disease represents simple, rapid and inexpensive method that can be used at the primary health care levels. In this study we have compared sensitivity of two PPE proteins of M. tuberculosis, i.e., Rv0256c and Rv1168c for their use as serodiagnostic markers in active tuberculosis patients. Employing a standardized enzyme immunoassay with these PPE proteins as candidate antigens we were able to successfully discriminate the TB patients' sera from the BCG-vaccinated healthy controls. Further, we observed that Rv1168c displayed higher sensitivity in detecting extrapulmonary and smear negative pulmonary TB cases which are difficult to diagnose by available diagnostic methods. Overall the study highlights that Rv1168c can be used as a potential serodiagnostic marker for the diagnosis of active tuberculosis disease. PMID:26364913

  12. Promoting regular physical activity in pulmonary rehabilitation.

    PubMed

    Garcia-Aymerich, Judith; Pitta, Fabio

    2014-06-01

    Patients with chronic respiratory diseases are usually physically inactive, which is an important negative prognostic factor. Therefore, promoting regular physical activity is of key importance in reducing morbidity and mortality and improving the quality of life in this population. A current challenge to pulmonary rehabilitation is the need to develop strategies that induce or facilitate the enhancement of daily levels of physical activity. Because exercise training alone, despite improving exercise capacity, does not consistently generate similar improvements in physical activity in daily life, there is also a need to develop behavioral interventions that help to promote activity. PMID:24874131

  13. 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

  14. 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.

  15. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa.

    PubMed

    Lebina, Limakatso; Fuller, Nigel; Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Abraham, Pattamukkil; Variava, Ebrahim; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62-3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52-2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield. PMID:27493800

  16. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa

    PubMed Central

    Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62–3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52–2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield. PMID:27493800

  17. 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 ...

  18. Respiratory infections: pulmonary tuberculosis.

    PubMed

    Choby, Beth A; Hunter, Paul

    2015-02-01

    Family physicians can prevent mortality and disability due to pulmonary tuberculosis (TB) by identifying high-risk patients. Recognition of symptoms (eg, cough for 3 weeks or longer) helps prevent overlooked diagnoses because results of tuberculin skin tests and interferon-gamma release assays are negative in up to 25% and 21%, respectively, of severe acute cases. The typical x-ray findings of cavities, infiltrates, and lymphadenopathy are minimal among immunosuppressed patients. Cases of active TB must be reported to local or state health departments within 24 hours of diagnosis. Sputum acid-fast bacillus tests provide results within hours and help quantify bacterial load but are not highly sensitive, and infection with nontuberculous mycobacteria can cause positive test results. Sputum cultures are adequately sensitive, identify mycobacterial species, and provide organisms for antibiotic susceptibility testing but require weeks for results. Molecular detection of Mycobacterium tuberculosis and of antibiotic-resistant mutations can expedite diagnosis and management of drug-resistant TB. Management of active TB should include directly observed therapy. Standard 6-month therapy with rifampin, isoniazid, pyrazinamide, and ethambutol resolves infection in nearly all immunocompetent adults with pansensitive TB. Multidrug-resistant TB requires second-line antibiotics (eg, fluoroquinolones, linezolid) in individualized regimens lasting 2 years. Management of latent TB infection prevents progression to active TB disease, particularly if management is completed within 2 years of infection. PMID:25685923

  19. 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.

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

    PubMed

    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

  1. 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

  2. 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. PMID:26234295

  3. Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB

    PubMed Central

    Shenai, Shubhada; Ronacher, Katharina; Malherbe, Stefanus; Stanley, Kim; Kriel, Magdalena; Winter, Jill; Peppard, Thomas; Barry, Charles E.; Wang, Jing; Dodd, Lori E.; Via, Laura E.; Barry, Clifton E.; Walzl, Gerhard; Alland, David

    2016-01-01

    Introduction Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy. Methods Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the Ct (delta Ct), or a novel “percent closing of baseline Ct deficit” (percent closing) were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes. Results Xpert was positive in 29/95 (30.5%) of subjects at week 24; and positive one year after treatment in 8/64 (12.5%) successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity. Conclusions Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy. PMID:27508390

  4. Decreased Frequencies of Circulating CD4+ T Follicular Helper Cells Associated with Diminished Plasma IL-21 in Active Pulmonary Tuberculosis

    PubMed Central

    Kumar, Nathella Pavan; Sridhar, Rathinam; Hanna, Luke E.; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

    2014-01-01

    Background Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored. Aims/Methodology To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS. Results We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro. Conclusions Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets. PMID:25343703

  5. IMMUNOSUPPRESSION OF PULMONARY NATURAL KILLER ACTIVITY BY EXPOSURE TO OZONE

    EPA Science Inventory

    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. ulmonary atural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity...

  6. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26185484

  8. Activation of Calpain-2 by Mediators in Pulmonary Vascular Remodeling of Pulmonary Arterial Hypertension.

    PubMed

    Kovacs, Laszlo; Han, Weihong; Rafikov, Ruslan; Bagi, Zsolt; Offermanns, Stefan; Saido, Takaomi C; Black, Stephen M; Su, Yunchao

    2016-03-01

    Calpain mediates collagen synthesis and cell proliferation and plays an important role in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). In the present study, we investigated whether and how calpain is activated by PAH mediators in pulmonary artery smooth muscle cells (PASMCs). These data show that smooth muscle-specific knockout of calpain attenuated and knockout of calpastatin potentiated pulmonary vascular remodeling and pulmonary hypertension. Treatment of PASMCs with the PAH mediators platelet-derived growth factor (PDGF), serotonin, H2O2, endothelin-1, and IL-6 caused significant increases in calpain activity, cell proliferation, and collagen-I protein level without changes in protein levels of calpain-1 and -2. The calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA/AM) did not affect calpain activation, but the extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 and knocking down of calpain-2 prevented calpain activation in PAH mediator-treated PASMCs. Mass spectrometry data showed that the phosphorylation of calpain-2 at serine (Ser) 50 was increased and the phosphorylation of calpain-2 at Ser369 was decreased in PDGF-treated PASMCs. The PDGF-induced increase in Ser50 phosphorylation of calpain-2 was prevented by PD98059, whereas dephosphorylation of calpain-2 at Ser369 was blocked by the protein phosphatase 2A inhibitor fostriecin. Furthermore, smooth muscle of pulmonary arteries in PAH animal models and patients with PAH showed higher levels of phospho-Ser50-calpain-2 (P-Ser50) and lower levels of phospho-Ser369-calpain-2 (P-Ser369). These data support that calpain modulates pulmonary vascular remodeling in PAH. PAH mediator-induced activation of calpain is caused by ERK1/2-dependent phosphorylation of calpain-2 at Ser50 and protein phosphatase 2A-dependent dephosphorylation of calpain-2 at Ser369 in pulmonary vascular remodeling of PAH. PMID:26248159

  9. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Overview In developed countries, such as the ... thought to be infected with TB bacteria, Mycobacterium tuberculosis ( Mtb ). TB is a chronic bacterial infection. It ...

  10. 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

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

    PubMed

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

    2016-05-01

    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

  12. Risk of Active Tuberculosis in HIV-Infected Patients in Taiwan with Free Access to HIV Care and a Positive T-Spot.TB Test

    PubMed Central

    Sun, Hsin-Yun; Hsueh, Po-Ren; Liu, Wen-Chun; Su, Yi-Ching; Chang, Sui-Yuan; Hung, Chien-Ching; Chang, Shan-Chwen

    2015-01-01

    Background Interferon-gamma release assays (IGRAs) have been used to identify individuals at risk for developing active tuberculosis (TB). However, data regarding the risk of TB development in HIV-infected patients testing positive for IGRAs remain sparse in the era of combination antiretroviral therapy. Methods Between 2011 and 2013, 608 HIV-infected patients without active TB undergoing T-Spot.TB testing were enrolled in this prospective observational study at a university hospital designated for HIV care in Taiwan with a declining TB incidence from 72 per 100,000 population in 2005 to 53 per 100,000 population in 2012. All of the subjects were followed until September 30, 2014. The national TB registry was accessed to identify any TB cases among those lost to follow-up. Results T-Spot.TB tested negative in 534 patients (87.8%), positive in 64 patients (10.5%), and indeterminate in 10 patients (1.6%). In multivariate analysis, positive T-Spot.TB was significantly associated with older age (adjusted odds ratio [AOR], 1.172 per 10-year increase; 95% confidence interval [CI], 1.022-1.344, P=0.023), past history of TB (AOR, 13.412; 95% CI, 6.106-29.460, P<0.001), and higher CD4 counts at enrollment (AOR, per 50-cell/μl increase, 1.062; 95% CI, 1.017-1.109, P=0.007). Of the 64 patients testing positive for T-Spot.TB, none received isoniazid preventive therapy and all but 5 received combination antiretroviral therapy at the end of follow-up with the latest CD4 count and plasma HIV RNA load being 592.8 cells/μL and 1.85 log10 copies/mL, respectively. One patient (1.6%) developed active TB after 167 person-years of follow-up (PYFU), resulting in an incidence rate of 0.599 per 100 PFYU. None of the 534 patients testing negative for T-Spot.TB developed TB after 1380 PYFU, nor did the 24 patients with old TB and positive T-Spot.TB tests develop TB after 62.33 PYFU. Conclusions The risk of developing active TB in HIV-infected patients with positive T-Spot.TB receiving

  13. Cytokine and Antibody Based Diagnostic Algorithms for Sputum Culture-Positive Pulmonary Tuberculosis

    PubMed Central

    Fleming, Joy; Chen, Liang; Wang, Yunxia; Li, Haicheng; Guo, Huixin; Zhou, Jie; Chen, Xunxun; Chen, Yuhui; Liao, Qinghua; Shu, Yang; Tan, Yaoju; Yu, Meiling; Li, Guozhou; Zhou, Lin; Zhong, Qiu; Bi, Lijun; Guo, Lina; Zhao, Meigui

    2015-01-01

    Background Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples. Methods TB-related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods. Results Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%). Conclusions Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical

  14. Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

    PubMed

    Nyhan, D P; Clougherty, P W; Goll, H M; Murray, P A

    1987-07-01

    Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3114215

  15. Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4+ and CD8+ T Cell Responses in a Process Dependent on IL-10

    PubMed Central

    George, Parakkal Jovvian; Anuradha, Rajamanickam; Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

    2014-01-01

    Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4+ and CD8+ T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections—Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4+ and CD8+ T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial–specific frequencies of mono- and multi–functional CD4+ Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4+ and CD8+ T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4+ T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4+ Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4+ T cell responses as well as protective systemic cytokine responses in active pulmonary TB. PMID:25211342

  16. 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

  17. 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. PMID:26161676

  18. Notch Activation of Ca(2+) Signaling in the Development of Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension.

    PubMed

    Smith, Kimberly A; Voiriot, Guillaume; Tang, Haiyang; Fraidenburg, Dustin R; Song, Shanshan; Yamamura, Hisao; Yamamura, Aya; Guo, Qiang; Wan, Jun; Pohl, Nicole M; Tauseef, Mohammad; Bodmer, Rolf; Ocorr, Karen; Thistlethwaite, Patricia A; Haddad, Gabriel G; Powell, Frank L; Makino, Ayako; Mehta, Dolly; Yuan, Jason X-J

    2015-09-01

    Hypoxic pulmonary vasoconstriction (HPV) is an important physiological response that optimizes the ventilation/perfusion ratio. Chronic hypoxia causes vascular remodeling, which is central to the pathogenesis of hypoxia-induced pulmonary hypertension (HPH). We have previously shown that Notch3 is up-regulated in HPH and that activation of Notch signaling enhances store-operated Ca(2+) entry (SOCE), an important mechanism that contributes to pulmonary arterial smooth muscle cell (PASMC) proliferation and contraction. Here, we investigate the role of Notch signaling in HPV and hypoxia-induced enhancement of SOCE. We examined SOCE in human PASMCs exposed to hypoxia and pulmonary arterial pressure in mice using the isolated perfused/ventilated lung method. Wild-type and canonical transient receptor potential (TRPC) 6(-/-) mice were exposed to chronic hypoxia to induce HPH. Inhibition of Notch signaling with a γ-secretase inhibitor attenuates hypoxia-enhanced SOCE in PASMCs and hypoxia-induced increase in pulmonary arterial pressure. Our results demonstrate that hypoxia activates Notch signaling and up-regulates TRPC6 channels. Additionally, treatment with a Notch ligand can mimic hypoxic responses. Finally, inhibition of TRPC6, either pharmacologically or genetically, attenuates HPV, hypoxia-enhanced SOCE, and the development of HPH. These results demonstrate that hypoxia-induced activation of Notch signaling mediates HPV and the development of HPH via functional activation and up-regulation of TRPC6 channels. Understanding the molecular mechanisms that regulate cytosolic free Ca(2+) concentration and PASMC proliferation is critical to elucidation of the pathogenesis of HPH. Targeting Notch regulation of TRPC6 will be beneficial in the development of novel therapies for pulmonary hypertension associated with hypoxia. PMID:25569851

  19. Diagnostics for pulmonary tuberculosis.

    PubMed

    Cudahy, Patrick; Shenoi, Sheela V

    2016-04-01

    Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID:27005271

  20. Diagnostics for pulmonary tuberculosis

    PubMed Central

    Cudahy, Patrick

    2016-01-01

    Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID:27005271

  1. Stereochemical Analysis of Leubethanol, an Anti-TB Active Serrulatane, from Leucophyllum frutescens

    PubMed Central

    Molina-Salinas, Gloria M.; Rivas-Galindo, Verónica M.; Said-Fernández, Salvador; Lankin, David C.; Muñoz, Marcelo A.; Joseph-Nathan, Pedro; Pauli, Guido F.; Waksman, Noemí

    2013-01-01

    Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens (Berl.) I.M. Johnst. led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25–12.50 µg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, 1H-NMR full spin analysis, as well as by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers. PMID:21859082

  2. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Research The New Challenge for TB Research NIAID ... HIV/AIDS Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Research Agenda (PDF) TB Research at NIAID Research ...

  3. Photoluminescence of Tb 3+ and Mn 2+ activated Ca 8MgGd(PO 4) 7 under vacuum ultraviolet excitation

    NASA Astrophysics Data System (ADS)

    Zhang, Jia; Wang, Yuhua; Huang, Yan

    2011-06-01

    Novel Tb 3+ and Mn 2+ activated Ca 8MgGd(PO 4) 7 phosphors were synthesized by solid-state reaction and their photoluminescence properties in vacuum ultraviolet region were investigated for the first time. It can be observed from the excitation spectra that the host-related absorption band is located around 170 nm, and it overlaps the O 2- → Tb 3+ charge transfer band of Ca 8MgGd(PO 4) 7:Tb 3+ around 161 nm and the 3d 5 → 3d 44s transition band of Ca 8MgGd(PO 4) 7:Mn 2+ near 200 nm. The 4f-4f 5d spin-allowed and spin-forbidden transitions of Tb 3+ are verified to be located at 170-250 and 257-271 nm, respectively. Upon 147 nm excitation, the dominant emission peak intensity of the Ca 8MgGd 0.1(PO 4) 7:0.9Tb 3+ phosphor is about 2.7 times stronger than that of the commercial Zn 2SiO 4:Mn 2+ green phosphor, and the brightness of the former with a short decay time of 2.5 ms is about 98% of the latter's. The Ca 8MgGd(PO 4):Mn 2+ phosphor excited at 147 nm exhibits a deep red emission around 650 nm, which could be attributed to the 4T 1 → 6A 1 transition of Mn 2+, with the CIE index (0.679, 0.321). In a word, the results above indicate that both Tb 3+ and Mn 2+ activated Ca 8MgGd(PO 4) 7 phosphors could be promising for PDP or Hg-free lamp applications.

  4. Association of the FCN2 Gene Single Nucleotide Polymorphisms with Susceptibility to Pulmonary Tuberculosis

    PubMed Central

    Jiang, Feng; Wei, Li-Liang; Shi, Li-Ying; Yu, Xiao-Mei; Liu, Chang-Ming; Liu, Xue-Hong; Feng, Xian-Min; Ping, Ze-Peng; Jiang, Ting-Ting; Chen, Zhong-Liang; Li, Zhong-Jie; Li, Ji-Cheng

    2015-01-01

    Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r2 > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective. PMID:26379154

  5. Mechanoelectrical feedback regulates the arrhythmogenic activity of pulmonary veins

    PubMed Central

    Chang, S‐L; Chen, Y‐C; Chen, Y‐J; Wangcharoen, W; Lee, S‐H; Lin, C‐I; Chen, S‐A

    2007-01-01

    Background Atrial fibrillation is commonly associated with dilated pulmonary veins. Stretch has been shown to have mechano‐electrical effects. Objective To investigate whether stretch can increase the arrhythmogenic activity of the pulmonary veins. Methods The transmembrane action potentials were recorded from rabbit pulmonary veins before and after stretch (100 and 300 mg). Gadolinium and streptomycin (stretch‐activated ion channel blockers) were each perfused into the pulmonary veins under a 300‐mg stretch. Results Stretch (0, 100 and 300 mg) force dependently increased the incidence of spontaneous activity (22%, 48% and 83%; p<0.05), mean (standard deviation (SD)) firing rates of spontaneous activity (1.7 (0.2), 2.1 (0.3) and 3 (0.2) Hz; p<0.05) and incidence of early post‐depolarisations (9%, 26% and 61%; p<0.05) and delayed post‐depolarisations (0%, 4% and 30%; p<0.05) in 23 pulmonary veins. In the seven preparations with spontaneous activity after the 300‐mg stretch, gadolinium (1, 3 and 10 μmol/l) decreased the incidence of spontaneous activity by 43%, 29% and 14%, respectively (p<0.05), and decreased the firing rate from 2.9 (0.1) Hz to 0.8 (0.4), 0.3 (0.1) and 0.1 (0.1) Hz, respectively (p<0.05). Streptomycin (10 and 40 μmol/l) decreased the incidence of spontaneous activity by 71% and 29%, respectively (p<0.05), and decreased the firing rate from 2.9 (0.1) Hz to 1.6 (0.4) and 0.5 (0.3) Hz, respectively (p<0.05). Conclusion Stretch is an important factor in the electrical activity of the pulmonary vein. Stretch‐induced arrhythmogenic activity of the pulmonary vein may contribute to the genesis of atrial fibrillation. PMID:16905626

  6. HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide.

    PubMed

    Montales, Maria Theresa; Chaudhury, Arun; Beebe, Alexandria; Patil, Sowmya; Patil, Naveen

    2015-01-01

    The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV-Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority. PMID:26779470

  7. HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide

    PubMed Central

    Montales, Maria Theresa; Chaudhury, Arun; Beebe, Alexandria; Patil, Sowmya; Patil, Naveen

    2015-01-01

    The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV–Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority. PMID:26779470

  8. The in vivo expressed Mycobacterium tuberculosis (IVE-TB) antigen Rv2034 induces CD4⁺ T-cells that protect against pulmonary infection in HLA-DR transgenic mice and guinea pigs.

    PubMed

    Commandeur, Susanna; van den Eeden, Susan J F; Dijkman, Karin; Clark, Simon O; van Meijgaarden, Krista E; Wilson, Louis; Franken, Kees L M C; Williams, Ann; Christensen, Dennis; Ottenhoff, Tom H M; Geluk, Annemieke

    2014-06-17

    Tuberculosis (TB) remains a life-threatening infectious disease of global proportions with serious negative health and economic consequences. The lack of sufficient protection induced by Mycobacterium bovis BCG, the current vaccine for TB, as well as the impact of HIV co-infection and the emergence of drug resistant Mycobacterium tuberculosis (Mtb) strains all urge for improved vaccines against TB. A minimal requirement for Mtb vaccine antigens is their in vivo expression during Mtb infection and ability to trigger significant immune responses. Recently we identified a new class of Mtb antigens, designated IVE-TB (in vivo expressed) antigens. These included Rv2034, a protein that was expressed during pulmonary infection and strongly recognized by human T-cells. Here, the in vivo immunogenicity and protective efficacy of Rv2034 was further analyzed using HLA-DR transgenic mice that lack endogenous murine MHC class II molecules. The Rv2034 protein indeed was highly immunogenic in HLA-DR3 transgenic mice and induced HLA-DR3 restricted IFN-γ(+)/TNF(+) and IFN-γ(+) CD4(+) T-cells, specific for an epitope encoded in peptide 31-50. CD4(+) T-cell responses were optimally induced when using TLR9- and TLR3-ligand-adjuvants or CAF09. Rv2034-specific antibodies were observed following immunization with either TLR2-, TLR3-, TLR4-, TLR5-, TLR7- or TLR9-ligands or CAF09. Importantly, immunization with Rv2034 or the hybrid-protein Ag85B-ESAT6-Rv2034 adjuvanted with CpG or CAF09, induced over one log reduction, relative to unvaccinated controls, in the number of bacilli in the lungs of Mtb challenged HLA-DR3 transgenic mice and guinea pigs. These data demonstrate the potential of Rv2034 as a novel, IVE-TB antigen for future TB vaccination. PMID:24837764

  9. 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.

  10. Discordance of Tuberculin Skin Test and Interferon Gamma Release Assay in Recently Exposed Household Contacts of Pulmonary TB Cases in Brazil

    PubMed Central

    Ribeiro-Rodrigues, Rodrigo; Kim, Soyeon; Coelho da Silva, Flávia Dias; Uzelac, Aleksandra; Collins, Lauren; Palaci, Moíses; Alland, David; Dietze, Reynaldo; Ellner, Jerrold J.; Jones-López, Edward; Salgame, Padmini

    2014-01-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8–12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion. PMID:24819060

  11. 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

  12. 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. PMID:25755701

  13. Luminescence properties of Ce3+ and Tb3+ co-activated ZnAl2O4 phosphor

    NASA Astrophysics Data System (ADS)

    Tshabalala, K. G.; Cho, S.-H.; Park, J.-K.; Pitale, Shreyas S.; Nagpure, I. M.; Kroon, R. E.; Swart, H. C.; Ntwaeaborwa, O. M.

    2012-05-01

    In this study, a solution combustion method was used to prepare green emitting Ce3+-Tb3+ co-activated ZnAl2O4 phosphor. The samples were annealed at 700 °C in air or hydrogen atmosphere to improve their crystallinity and optical properties. X-ray diffraction study confirmed that both as-prepared and post-preparation annealed samples crystallized in the well known cubic spinel structure of ZnAl2O4. An agglomeration of irregular platelet-like particles whose surfaces were encrusted with smaller spheroidal particles was confirmed by scanning electron microscopy (SEM). The fluorescence data collected from the annealed samples with different concentrations of Ce3+ and Tb3+ show the enhanced green emission at 543 nm associated with 5D4→7F5 transitions of Tb3+. The enhancement was attributed to energy transfer from Ce3+ to Tb3+. Possible mechanism of energy transfer via a down conversion process is discussed. Furthermore, cathodoluminescence (CL) intensity degradation of this phosphor was also investigated and the degradation data suggest that the material was chemically stable and the CL intensity was also stable after 10 h of irradiation by a beam of high energy electrons.

  14. 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

  15. Outcomes of a clinical diagnostic algorithm for management of ambulatory smear and Xpert MTB/Rif negative HIV infected patients with presumptive pulmonary TB in Uganda: a prospective study

    PubMed Central

    Walusimbi, Simon; Semitala, Fred; Bwanga, Freddie; Haile, Melles; De Costa, Ayesha; Davis, Lucian; Joloba, Moses; Hoffner, Sven; Kamya, Moses

    2016-01-01

    Introduction Diagnostic guidelines for Tuberculosis (TB) in HIV infected patients previously relied on microscopy where the value of initial antibiotic treatment for exclusion of pulmonary TB (PTB) was limited. New guidelines rely on the Xpert MTB Rif test (Xpert). However, the value of the antibiotic treatment remains unclear particularly in individuals who are smear-negative and Xpert-negative-given Xpert has only moderate sensitivity for smear-negative PTB. We assessed an algorithm involving initial treatment with antibiotics prior empiric TB treatment in HIV patients with presumptive PTB who were both smear and Xpert negative. Methods We performed a prospective study with six month follow-up to establish patient response to a course of broad spectrum antibiotics prior empiric TB treatment between March 2012 and June 2013. We calculated the proportion of patients who responded to the antibiotic treatment and those who did not. We computed the crude and adjusted odds ratios with their 95% confidence intervals, for response to the antibiotic treatment on various patient characteristics. We report treatment outcomes for patients who received broad spectrum antibiotics only or who were initiated empiric TB treatment. Results Our cohort comprised 162 smear-negative and Xpert-negative patients, of whom 59% (96 of 162) were female, 81% (131 of 162) were on antiretroviral therapy (ART) for a median of 8.7 months. Overall, 88% (141 of 160) responded to the antibiotic treatment, 8% (12 of 160) got empiric TB treatment and 4% (7 out of 160) were treated for other respiratory disease. The odds of improvement on antibiotics were lower in patients with advanced HIV disease than in patients with early HIV disease. Adjusted odds ratios were significant for HIV clinical stage (AOR; 0.038,) and duration on ART (AOR; 1.038,). Conclusion The majority of HIV patients with presumptive PTB with smear-negative and Xpert negative results improved on the antibiotic treatment and did not

  16. Cytotoxic activity of dendritic cells as a possible mechanism of negative regulation of T lymphocytes in pulmonary tuberculosis.

    PubMed

    Sakhno, Ludmila V; Tikhonova, Marina A; Tyrinova, Tamara V; Leplina, Olga Yu; Shevela, Ekaterina Ya; Nikonov, Sergey D; Zhdanov, Oleg A; Ostanin, Alexander A; Chernykh, Elena R

    2012-01-01

    The PD-1/B7-H1-mediated induction of T cell apoptosis/anergy as a possible mechanism of immune response failure was studied in 76 patients with pulmonary tuberculosis (TB) with normal and low-proliferative response to antigens of M. tuberculosis (purified protein derivative (PPD)). It was revealed that dendritic cells (DCs), generated in vitro from patient blood monocytes with GM-CSF + IFN-α, were characterized by increased B7-H1 expression, upproduction of IL-10, and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). Moreover, DCs of patients with TB were able to enhance T cell apoptosis and to block T-cell division in MLC. It was shown that neutralizing anti-PD1 antibodies significantly decreased the proapoptogenic/tolerogenic effect of DCs. Correlation analysis revealed a direct relationship between IL-10 production and level of B7-H1 expression in the general group of investigated patients. It was demonstrated that generation of healthy donor DCs in the presence of IL-10 led to an increase in the number of DCs-expressed B7-H1 molecule, DC proapoptogenic activity, and a decrease in their allostimulatory activity. Obviously, the revealed phenomenon of the PD-1/B7-H1-mediated pro-apoptogenic activity of DCs is clinically significant since the cytotoxic/tolerogenic potential of DCs is more pronounced in patients with PPD anergy. PMID:23056139

  17. Towards new TB vaccines: What are the challenges?

    PubMed

    Dockrell, Hazel M

    2016-06-01

    New and effective tuberculosis (TB) vaccines are urgently needed to control pulmonary TB, and in particular to prevent the spread of drug-resistant strains of Mycobacterium tuberculosis. These drug-resistant strains can range from those resistant to first-line drugs to those that are almost impossible to treat. To develop new and effective vaccines for HIV and malaria has been difficult and it is proving to be just as challenging for TB. TB is a complicated disease with a spectrum from apparently controlled latent infection to active clinical disease and so different types of preventive or post-exposure vaccine may be needed. Identifying the most promising vaccine candidates to move into clinical trials is difficult, as we lack biomarker signatures that can predict protective efficacy. There is a risk that the failure of the MVA-85A vaccine to show efficacy when given to previously BCG-vaccinated South African infants will impact on the resources available for the development and trials of other candidate TB vaccines. Continued support for the development of new TB vaccines should remain a priority as an effective vaccine would bring huge public health benefits. PMID:26960944

  18. Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

    PubMed Central

    Kassa, Desta; Ran, Leonie; Geberemeskel, Wudneh; Tebeje, Mekashaw; Alemu, Amelewerk; Selase, Alemayehu; Tegbaru, Belete; Franken, Kees L. M. C.; Friggen, Annemieke H.; van Meijgaarden, Krista E.; Ottenhoff, Tom H. M.; Wolday, Dawit; Messele, Tsehaynesh

    2012-01-01

    Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n = 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics

  19. Peroxynitrite has potent pulmonary vasodilator activity in the rat.

    PubMed

    Casey, David B; Pankey, Edward A; Badejo, Adeleke M; Bueno, Franklin R; Bhartiya, Manish; Murthy, Subramanyam N; Uppu, Rao M; Nossaman, Bobby D; Kadowitz, Philip J

    2012-04-01

    Peroxynitrite (PN) worsens pathological conditions associated with oxidative stress. However, beneficial effects have also been reported. PN has been shown to demonstrate vasodilator as well as vasoconstrictor properties that are dependent upon the experimental conditions and the vascular bed studied. PN-induced vascular smooth muscle relaxation may involve the formation of nitric oxide (NO) donors. The present results show that PN has significant vasodilator activity in the pulmonary and systemic vascular beds, and that responses to PN were not attenuated by L-penicillamine (L-PEN), a PN scavenger, whereas responses to sodium nitroprusside (SNP) were decreased. PN had a small inhibitory effect on decreases in arterial pressure in response to the NO donors diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) and S-nitrosoglutathione (GSNO). PN partially reversed hypoxic pulmonary vasoconstriction. PN responses were attenuated by the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and responses to PN and the PN precursor, 3-morpholinosydnonimine (SIN-1), were different. These data show that PN has potent pulmonary vasodilator activity in the rat, and provide evidence that a PN interaction with S-nitrosothiols is not the major mechanism mediating the response. These data suggest that responses to PN are mediated by the activation of sGC, and that PN has a small inhibitory effect on NO responses. PMID:22452357

  20. Health system barriers to implementation of collaborative TB and HIV activities including prevention of mother to child transmission in South Africa.

    PubMed

    Uwimana, J; Jackson, D; Hausler, H; Zarowsky, C

    2012-05-01

    In South Africa, the control of TB and HIV co-infection remains a major challenge despite the availability of international and national guidelines for integration of TB and HIV services. This study was undertaken in KwaZulu-Natal, one of the provinces most affected by both TB and HIV, to identify and understand managers' and community care workers' (CCWs) perceptions of health systems barriers related to the implementation of collaborative TB/HIV activities, including prevention of mother to child transmission of HIV (PMTCT). We conducted 29 in-depth interviews with health managers at provincial, district and facility level and with managers of NGOs involved in TB and HIV care, as well as six focus group discussions with CCWs. Thematic analysis of transcripts revealed a convergence of perspectives on the process and the level of the implementation of policy directives on collaborative TB and HIV activities across all categories of respondents (i.e. province-, district-, facility- and community-based organizations). The majority of participants felt that the implementation of the policy was insufficiently consultative and that leadership and political will were lacking. The predominant themes related to health systems barriers include challenges related to structure and organisational culture; management, planning and power issues; unequal financing; and human resource capacity and regulatory problems notably relating to scope of practice of nurses and CCWs. Accelerated implementation of collaborative TB/HIV activities including PMTCT will require political will and leadership to address these health systems barriers. PMID:22394016

  1. Pechini synthesis of lanthanide (Eu3+/Tb3+or Dy3+) ions activated BaGd2O4 nanostructured phosphors: an approach for tunable emissions.

    PubMed

    Seeta Rama Raju, G; Pavitra, E; Yu, Jae Su

    2014-09-14

    Trivalent lanthanide (Eu(3+), Tb(3+) and Dy(3+)) ions activated tunable color emitting BaGd2O4 (BG) phosphors were synthesized by a facile Pechini-type sol-gel process. The X-ray diffraction pattern confirmed the orthorhombic phase after annealing at 1300 °C for 5 h. Morphological studies were performed based on the analysis of transmission electron microscopy images, which showed needle type nanorods. The BG phosphor exhibited good photoluminescence (PL) properties in the respective regions when doped with Eu(3+), Tb(3+) and Dy(3+) ions. The Eu(3+) co-activated BG:Tb(3+) phosphor yielded tunable emissions including tri-band established white light emission based on the co-activator concentration and excitation wavelength. The energy transfer from Tb(3+) to Eu(3+) ions was controlled by selecting a suitable excitation wavelength and the decay measurements were carried out for analyzing the energy transfer efficiency. The cathodoluminescence properties of these phosphors were almost similar to PL properties when doped with individual Eu(3+), Tb(3+), and Dy(3+) ions, but were different when co-doped with Eu(3+)/Tb(3+) or Eu(3+)/Dy(3+) ions. In the case of Eu(3+)/Tb(3+) doped samples, the energy transfer process occurred unlike the PL channel. The calculated Commission International de l'Eclairage chromaticity coordinates of individual ion doped BG phosphors confirmed red, green, and white emissions and for co-doped samples they showed tunable emission. PMID:25052006

  2. Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

    PubMed Central

    Sathyamoorthy, Tarangini; Sandhu, Gurjinder; Tezera, Liku B.; Thomas, Richard; Singhania, Akul; Woelk, Christopher H.; Dimitrov, Borislav D.; Agranoff, Dan; Evans, Carlton A. W.; Friedland, Jon S.; Elkington, Paul T.

    2015-01-01

    Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers. PMID:25635689

  3. Blunted activation of Rho-kinase in yak pulmonary circulation.

    PubMed

    Ishizaki, Takeshi; Mizuno, Shiro; Sakai, Akio; Matsukawa, Shigeru; Kojonazarov, Baktybek; Zamirbek, Baiserkeev; Umeda, Yukihiro; Morikawa, Miwa; Anzai, Masaki; Ishizuka, Tamotsu; Aldashev, Almaz

    2015-01-01

    Yaks have adapted to high altitude and they do not develop hypoxic pulmonary hypertension. Although we previously identified the important role of augmented nitric oxide synthase activity in the yak pulmonary circulatory system, evidence of the direct involvement of Rho-kinase as a basal vascular tone regulator is lacking. Four domesticated male pure-bred yaks and four bulls that were born and raised at an altitude of 3000 m in the Tien-Shan mountains were studied at an altitude of 3,100 m. Mean pulmonary artery pressure (mPAP) was measured before and after fasudil (60 mg in 20 mL of saline) was intravenously administered using a Swan-Ganz catheter at a rate of 3.3 mL/min for 30 min. Fasudil decreased mPAP in bulls from 67.8±14.9 to 32.3±5.3 mmHg (P < 0.05) after 15 min and the level was maintained for 30 min, but it merely blunted mPAP in yaks from 28.2±4.5 to 25.1±11.1 and 23.2±2.7 mmHg after 5 and 30 min, respectively. These findings comprise the first evidence of a modest role of Rho-kinase in the maintenance of pulmonary artery pressure in the yak. PMID:25654121

  4. Blunted Activation of Rho-Kinase in Yak Pulmonary Circulation

    PubMed Central

    Sakai, Akio; Matsukawa, Shigeru; Zamirbek, Baiserkeev; Umeda, Yukihiro; Morikawa, Miwa; Anzai, Masaki; Ishizuka, Tamotsu; Aldashev, Almaz

    2015-01-01

    Yaks have adapted to high altitude and they do not develop hypoxic pulmonary hypertension. Although we previously identified the important role of augmented nitric oxide synthase activity in the yak pulmonary circulatory system, evidence of the direct involvement of Rho-kinase as a basal vascular tone regulator is lacking. Four domesticated male pure-bred yaks and four bulls that were born and raised at an altitude of 3000 m in the Tien-Shan mountains were studied at an altitude of 3,100 m. Mean pulmonary artery pressure (mPAP) was measured before and after fasudil (60 mg in 20 mL of saline) was intravenously administered using a Swan-Ganz catheter at a rate of 3.3 mL/min for 30 min. Fasudil decreased mPAP in bulls from 67.8±14.9 to 32.3±5.3 mmHg (P < 0.05) after 15 min and the level was maintained for 30 min, but it merely blunted mPAP in yaks from 28.2±4.5 to 25.1±11.1 and 23.2±2.7 mmHg after 5 and 30 min, respectively. These findings comprise the first evidence of a modest role of Rho-kinase in the maintenance of pulmonary artery pressure in the yak. PMID:25654121

  5. 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. PMID:27196627

  6. 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

  7. Alteration of biophysical activity of pulmonary surfactant by aluminosilicate nanoparticles.

    PubMed

    Kondej, Dorota; Sosnowski, Tomasz R

    2013-02-01

    The influence of five different types of aluminosilicate nanoparticles (NPs) on the dynamic surface activity of model pulmonary surfactant (PS) (Survanta) was studied experimentally using oscillating bubble tensiometry. Bentonite, halloysite and montmorillonite (MM) NPs, which are used as fillers of polymer composites, were characterized regarding the size distribution, morphology and surface area. Particle doses applied in the studies were estimated based on the inhalation rate and duration, taking into account the expected aerosol concentration and deposition efficiency after penetration of NPs into the alveolar region. The results indicate that aluminosilicate NPs at concentrations in the pulmonary liquid above 0.1 mg cm(-3) are capable of promoting alterations of the original dynamic biophysical activity of the PS. This effect is indicated by deviation of the minimum surface tension, stability index and the size of surface tension hysteresis. Such response is dependent on the type of NPs present in the system and is stronger when particle concentration increases. It is suggested that interactions between NPs and the PS must be related to the surfactant adsorption on the suspended particles, while in the case of surface-modified clay NPs the additional washout of surface-active components may be expected. It is speculated that observed changes in surface properties of the surfactant may be associated with undesired health effects following extensive inhalation of aluminosilicate NPs in the workplace. PMID:23363039

  8. 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 ...

  9. Modulation of pulmonary macrophage superoxide release and tumoricidal activity following activation by biological response modifiers.

    PubMed

    Drath, D B

    1986-10-01

    Following immunologic activation, pulmonary macrophages may prevent or cause regression of lung metastases by mechanisms which remain largely unknown. The studies described here were designed to determine if enhanced oxygen metabolite release was related to postactivation tumoricidal activity. We have shown that in vitro activation of Fischer 344 rat pulmonary macrophages by either free or liposome-encapsulated muramyl dipeptide leads to both enhanced release of superoxide anions and marked tumoricidal activity against syngenic (Fischer 13762), allogeneic (Schmidt-Ruppin RR 1022) and xenogeneic (Fibrosarcoma MCA-F) 125I-deoxyuridine-labeled target cells. This immune modulator did not, however, metabolically activate pulmonary macrophages as effectively as liposome-encapsulated lipopolysaccharide. A 24-h in vitro incubation with either 150 U or 300 U of interferon-gamma (3 X 10(6) U/mg) or 30 U, 150 U or 300 U of interferon-alpha (6 X 10(5) U/mg) caused a significant elevation in superoxide release above controls, whereas short-term exposure (2 or 4 h) had little or no effect. Free or encapsulated 6-O-stearoyl muramyl dipeptide, on the other hand, did increase superoxide levels at all 3 time periods. When either interferon-gamma or free or encapsulated muramyl dipeptide derivative were administered to intact rats by either i.v. injection, intratracheal instillation or osmotic minipump infusion, pulmonary macrophage tumoricidal activity was observed 96 h after cell harvesting. Zymosan-stimulated superoxide release, however, was not consistently elevated above control or empty liposome treatment following this course of in vivo activation. The data collectively suggest that in vivo pulmonary macrophage activation to a tumoricidal state and metabolic activation resulting in enhanced superoxide may be separable events. PMID:3021650

  10. 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. PMID:20478515

  11. 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

  12. A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients

    PubMed Central

    Hölscher, Christoph; Heitmann, Lisa; Owusu-Dabo, Ellis; Horstmann, Rolf D.; Meyer, Christian G.; Ehlers, Stefan; Thye, Thorsten

    2016-01-01

    The contribution of interleukin- (IL-) 4 receptor-alpha- (Rα-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent Mtb replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4Rα completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the IL4, IL13, IL4RA, IL13RA1, and IL13RA2 genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB. In fact, the structural variant of the IL4RA I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of IL13RA2 was associated with disease in females. To evaluate whether the human-like TB pathology in IL-13-overexpressing mice is specifically mediated through the IL-4Rα subunit, we analyzed IL-13 transgenic mice with a genetic ablation of the IL-4Rα. In these mice, the IL-13-mediated increased susceptibility, human-like pathology of collagen deposition around centrally necrotizing granulomas, and alternative macrophage activation were abolished. Together, our genetic association study in human TB patients further supports the assumption that IL-13/IL-4Rα-dependent mechanisms are involved in mediating tissue pathology of human TB. PMID:26977119

  13. Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

    PubMed

    Gupta, S; Granich, R; Date, A; Lepere, P; Hersh, B; Gouws, E; Samb, B

    2014-10-01

    Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count ⩿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries. PMID:25216827

  14. Multicolored, Tb³⁺-Based Antibody-Free Detection of Multiple Tyrosine Kinase Activities.

    PubMed

    Lipchik, Andrew M; Perez, Minervo; Cui, Wei; Parker, Laurie L

    2015-08-01

    Kinase signaling is a major mechanism driving many cancers. While many inhibitors have been developed and are employed in the clinic, resistance due to crosstalk and pathway reprogramming is an emerging problem. High-throughput assays to detect multiple pathway kinases simultaneously could better model these complex relationships and enable drug development to combat this type of resistance. We developed a strategy to take advantage of time-resolved luminescence of Tb(3+)-chelated phosphotyrosine-containing peptides, which facilitated efficient energy transfer to small molecule fluorophores conjugated to the peptides to produce orthogonally colored biosensors for two different kinases. This enabled multiplexed detection with high signal-to-noise in a high-throughput-compatible format. This proof-of-concept study provides a platform that could be applied to other lanthanide metal and fluorophore combinations to achieve even greater multiplexing without the need for phosphospecific antibodies. PMID:26207839

  15. ACTIVATION OF GATA-4 BY SEROTONIN IN PULMONARY ARTERY SMOOTH MUSCLE CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serotonin (5-HT) is a mitogen of pulmonary artery smooth muscle cells (PASMC) and plays an important role in the development of pulmonary hypertension. Signal transduction initiated by 5-HT involves serotonin transporter (SERT)-dependent generation of reactive oxygen species (ROS) and activation of...

  16. 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

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

    PubMed

    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

  18. Diaphragm activation during exercise in chronic obstructive pulmonary disease.

    PubMed

    Sinderby, C; Spahija, J; Beck, J; Kaminski, D; Yan, S; Comtois, N; Sliwinski, P

    2001-06-01

    Although it has been postulated that central inhibition of respiratory drive may prevent development of diaphragm fatigue in patients with chronic obstructive pulmonary disease (COPD) during exercise, this premise has not been validated. We evaluated diaphragm electrical activation (EAdi) relative to maximum in 10 patients with moderately severe COPD at rest and during incremental exhaustive bicycle exercise. Flow was measured with a pneumotachograph and volume by integration of flow. EAdi and transdiaphragmatic pressures (Pdi) were measured using an esophageal catheter. End-expiratory lung volume (EELV) was assessed by inspiratory capacity (IC) maneuvers, and maximal voluntary EAdi was obtained during these maneuvers. Minute ventilation (V E) was 12.2 +/- 1.9 L/min (mean +/- SD) at rest, and increased progressively (p < 0.001) to 31.0 +/- 7.8 L/min at end-exercise. EELV increased during exercise (p < 0.001) causing end-inspiratory lung volume to attain 97 +/- 3% of TLC at end-exercise. Pdi at rest was 9.4 +/- 3.2 cm H(2)O and increased during the first two thirds of exercise (p < 0.001) to plateau at about 13 cm H(2)O. EAdi was 24 +/- 6% of voluntary maximal at rest and increased progressively during exercise (p < 0.001) to reach 81 +/- 7% at end-exercise. In conclusion, dynamic hyperinflation during exhaustive exercise in patients with COPD reduces diaphragm pressure-generating capacity, promoting high levels of diaphragm activation. PMID:11401887

  19. Generation and application of ssDNA aptamers against glycolipid antigen ManLAM of Mycobacterium tuberculosis for TB diagnosis.

    PubMed

    Tang, Xiao-Lei; Wu, Shi-Min; Xie, Yan; Song, Neng; Guan, Qing; Yuan, Chunhui; Zhou, Xiang; Zhang, Xiao-Lian

    2016-05-01

    The development of effective Mycobacterial antigen diagnostic reagents remains a high priority. Mannose-capped lipoarabinomannan (ManLAM) is a lipoglycan serving as a major cell wall component. ManLAM is also an early released antigen in the blood circulation system during Mycobacteria tuberculosis (M.tb) infection and is a perfect target antigen for TB diagnosis. In this study, ssDNA aptamers "antibodies" against ManLAM of the predominant clinical epidemic M.tb Beijing genotype strains were generated by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technique. The selected single aptamer T9 demonstrated the highest specificity and binding affinity, with an equilibrium dissociation constant (Kd) of 668 ± 159 nmol/L. We further detected ManLAM antigens in serum and sputum samples from active pulmonary tuberculosis (aPTB) patients, extrapulmonary TB (EPTB) patients and healthy donors by using a T9 based enzyme-linked oligonucleotide assay (ELONA). The results showed that the specificity and sensitivity were 95.31% and 83.00% (for 100 aPTB serum samples), 98.70% and 92.71% (for 96 aPTB sputum samples), and 94.44% and 88.71% (for 62 EPTB serum samples), respectively. A good correlation was observed between the T9 aptamer-based ELONA and the clinical T-SPOT.TB. Thus, T9 based ELONA has potentials for diagnosis of TB, including inactive TB, smear-negative TB, EPTB, and TB with immunodeficiency, and assist the diagnosis of LTBI albeit it could not distinguish LTBI and active TB. PMID:26850356

  20. 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

  1. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia.

    PubMed

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

    2015-10-01

    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 (10(6) 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

  2. Daily activities are sufficient to induce dynamic pulmonary hyperinflation and dyspnea in chronic obstructive pulmonary disease patients

    PubMed Central

    Castro, Antonio A.M.; Kümpel, Claudia; Rangueri, Rosana Chaves; Oliveira, Maurício Dalcin; Dornelles, Rodrigo Alves; Brito, Emerson Roberto; Seki, Tânia Maria; Porto, Elias F

    2012-01-01

    OBJECTIVE: The aim of this study was to measure dynamic lung hyperinflation and its influence on dyspnea perception in moderate and severe chronic obstructive pulmonary disease patients after performing activities of daily living. METHODS: We measured inspiratory capacity, sensation of dyspnea, peripheral oxygen saturation, heart rate and respiratory rate in 19 chronic obstructive pulmonary disease patients. These measurements were taken at rest and after performing activities of daily living (e.g., going up and down a set of stairs, going up and down a ramp and sweeping and mopping a room). RESULT: The inspiratory capacity of patients at rest was significantly decreased compared to the capacity of patients after performing activities. The change in inspiratory capacity was -0.67 L after going up and down a ramp, -0.46 L after sweeping and mopping a room, and -0.55 L after climbing up and down a set of stairs. Dyspnea perception increased significantly between rest, sweeping and mopping, and going up and down a set of stairs. Dyspnea perception correlated positively with inspiratory capacity variation (r = 0.85) and respiratory rate (r = 0.37) and negatively with peripheral oxygen saturation (r = -0.28). CONCLUSION: Chronic obstructive pulmonary disease patients exhibited reductions in inspiratory capacity and increases in dyspnea perception during commonly performed activities of daily living, which may limit physical performance in these patients. PMID:22522756

  3. The contribution of the sympathetic nervous system to the immunopathology of experimental pulmonary tuberculosis.

    PubMed

    Barrios-Payán, Jorge; Revuelta, Alberto; Mata-Espinosa, Dulce; Marquina-Castillo, Brenda; Villanueva, Enrique Becerril; Gutiérrez, María Eugenia Hernández; Pérez-Sánchez, Gilberto; Pavón, Lenin; Hernandez-Pando, Rogelio

    2016-09-15

    The role of norepinephrine (NE) in the immunopathology of experimental tuberculosis (TB) was studied by measuring pulmonary NE and determining its cellular sources and targets. Functional studies were performed administrating adrenergic and anti-adrenergic drugs at different TB phases. Results showed high production of NE during early infection by adrenergic nerve terminals and lymphocytes located in the lungs and mediastinal lymph nodes, these cells highly expressed β2 adreno-receptors (β2AR) which by an autocrine mechanism promote Th-1 cell differentiation favoring protection. During advanced infection, the production of NE and β2AR sharply decreased, suggesting that adrenergic activity is less important during late TB. PMID:27609282

  4. Oxidative stress-dependent activation of collagen synthesis is induced in human pulmonary smooth muscle cells by sera from patients with scleroderma-associated pulmonary hypertension

    PubMed Central

    2014-01-01

    Pulmonary arterial hypertension is a major complication of systemic sclerosis. Although oxidative stress, intima hyperplasia and a progressive vessel occlusion appear to be clearly involved, the fine molecular mechanisms underpinning the onset and progression of systemic sclerosis-associated pulmonary arterial hypertension remain largely unknown. Here we shows for the first time that an increase of NADPH-derived reactive oxygen species production induced by sera from systemic sclerosis patients with pulmonary arterial hypertension drives collagen type I promoter activity in primary human pulmonary artery smooth muscle cells, suggesting that antioxidant-based therapies should be considered in the treatment of systemic sclerosis-associated vascular diseases. PMID:25085432

  5. Detection of Mycobacterium tuberculosis (MTB) in Fecal Specimens From Adults Diagnosed With Pulmonary Tuberculosis Using the Xpert MTB/Rifampicin Test

    PubMed Central

    Kokuto, Hiroyuki; Sasaki, Yuka; Yoshimatsu, Shoji; Mizuno, Kazue; Yi, Lina; Mitarai, Satoshi

    2015-01-01

    Background. The Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) is a fully automated diagnostic test that allows for the detection of MTB including its RIF resistance. Although the test is used for the diagnosis of tuberculosis (TB) in sputum samples worldwide, studies using fecal specimens are scarce. We therefore evaluated the efficacy of the Xpert MTB/RIF test for detection of MTB in fecal specimens obtained from adult pulmonary TB patients, confirmed by culture and/or molecular diagnostic methods. Methods. We conducted a retrospective case-control study to provide proof-of-concept regarding the efficacy of the Xpert MTB/RIF test using fecal samples for diagnosing pulmonary TB via detection of MTB in adult patients (≥20 years) at the Fukujuji Hospital in Tokyo, Japan. Results. Fecal specimens were obtained from 56 active pulmonary TB patients (including 48 sputum smear-positive and 8 sputum smear-negative patients), 10 non-TB patients (including 4 Myocobacterium avium complex infections), and 27 healthy individuals who were exposed to active pulmonary TB patients. The sensitivity of the fecal Xpert MTB/RIF was 100% (81.7%–100%) for detection of MTB in specimens from sputum smear-positive (1+ to 3+) patients, 81.0% (58.1%–94.6%) in specimens from sputum smear scanty positive patients, and 50.0% (15.7%–84.3%) in specimens from sputum smear-negative patients. Meanwhile, each of the fecal specimens from the non-TB group was negative for MTB (specificity 100%; 95% confidence interval, 86.2–100). Conclusions. The fecal Xpert MTB/RIF test could detect MTB in a large proportion of smear-positive pulmonary TB patients, without frequent false-positive results at a TB referral hospital in Japan. PMID:26125035

  6. Dextromethorphan Mediated Bitter Taste Receptor Activation in the Pulmonary Circuit Causes Vasoconstriction

    PubMed Central

    Upadhyaya, Jasbir D.; Chakraborty, Raja; Pydi, Sai P.; Bhullar, Rajinder P.; Dakshinamurti, Shyamala; Chelikani, Prashen

    2014-01-01

    Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways. PMID:25340739

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Physical Activity Counselling during Pulmonary Rehabilitation in Patients with COPD: A Randomised Controlled Trial

    PubMed Central

    Burtin, Chris; Langer, Daniel; van Remoortel, Hans; Demeyer, Heleen; Gosselink, Rik; Decramer, Marc; Dobbels, Fabienne; Janssens, Wim; Troosters, Thierry

    2015-01-01

    Background Pulmonary rehabilitation programs only modestly enhance daily physical activity levels in patients with chronic obstructive pulmonary disease (COPD). This randomised controlled trial investigates the additional effect of an individual activity counselling program during pulmonary rehabilitation on physical activity levels in patients with moderate to very severe COPD. Methods Eighty patients (66±7 years, 81% male, forced expiratory volume in 1 second 45±16% of predicted) referred for a six‐month multidisciplinary pulmonary rehabilitation program were randomised. The intervention group was offered an additional eight-session activity counselling program. The primary outcomes were daily walking time and time spent in at least moderate intense activities. Results Baseline daily walking time was similar in the intervention and control group (median 33 [interquartile range 16–47] vs 29 [17–44]) whereas daily time spent in at least moderate intensity was somewhat higher in the intervention group (17[4–50] vs 12[2–26] min). No significant intervention*time interaction effects were observed in daily physical activity levels. In the whole group, daily walking time and time spent in at least moderate intense activities did not significantly change over time. Conclusions The present study identified no additional effect of eight individual activity counselling sessions during pulmonary rehabilitation to enhance physical activity levels in patients with COPD. Trial Registration clinicaltrials.gov NCT00948623 PMID:26697853

  12. Activated STING in a Vascular and Pulmonary Syndrome

    PubMed Central

    Yang, D.; Ramsey, S.E.; Sanchez, G.A. Montealegre; Tenbrock, K.; Wittkowski, H.; Jones, O.Y.; Kuehn, H.S.; Lee, C.-C.R.; DiMattia, M.A.; Cowen, E.W.; Gonzalez, B.; Palmer, I.; DiGiovanna, J.J.; Biancotto, A.; Kim, H.; Tsai, W.L.; Trier, A.M.; Huang, Y.; Stone, D.L.; Hill, S.; Kim, H.J.; Hilaire, C. St.; Gurprasad, S.; Plass, N.; Chapelle, D.; Horkayne-Szakaly, I.; Foell, D.; Barysenka, A.; Candotti, F.; Holland, S.M.; Hughes, J.D.; Mehmet, H.; Issekutz, A.C.; Raffeld, M.; McElwee, J.; Fontana, J.R.; Minniti, C.P.; Moir, S.; Kastner, D.L.; Gadina, M.; Steven, A.C.; Wingfield, P.T.; Brooks, S.R.; Rosenzweig, S.D.; Fleisher, T.A.; Goldbach-Mansky, R.

    2014-01-01

    BACKGROUND The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-β, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mono-nuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibro-blasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients’ lymphocytes was

  13. Enhanced visible light photocatalytic activity of ZnO doped with down-conversion NaSrBO3:Tb(3+) phosphors.

    PubMed

    Liu, Xinjuan; Wang, Xiaojun; Li, Huili; Li, Jinliang; Pan, Likun; Zhang, Jing; Min, Guoquan; Sun, Zhuo; Sun, Changqing

    2015-01-01

    ZnO-NaSrBO3:Tb(3+) (ZNT) composites were successfully synthesized via microwave-assisted reaction of the ZnO precursor with a NaSrBO3:Tb(3+) suspension using a microwave synthesis system. The morphology, structure and photocatalytic performance in the degradation of methylene blue (MB) were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, UV-vis absorption spectroscopy, fluorescence spectrophotometry and electrochemical impedance spectroscopy, respectively. The results show that the ZNT composites exhibit enhanced photocatalytic activity in the degradation of MB with a maximum degradation rate of 97% under visible light irradiation compared with pure ZnO (12%), which is ascribed to the increased light absorption and the reduction of photoelectron-hole pair recombination in ZnO with the introduction of NaSrBO3:Tb(3+), as well as the light down-converting effect of NaSrBO3:Tb(3+), which facilitates the self-sensitized degradation of MB. PMID:25366251

  14. The effect of dextran to restore the activity of pulmonary surfactant inhibited by albumin.

    PubMed

    Lu, J J; Cheung, W W Y; Yu, L M Y; Policova, Z; Li, D; Hair, M L; Neumann, A W

    2002-04-01

    Pulmonary surfactant is crucial to maintain the proper functioning of the respiration system. Certain types of blood proteins (e.g. albumin) were found to inhibit the activity of pulmonary surfactant. Axisymmetric Drop Shape Analysis (ADSA) was used to study the effect of dextran to restore the activity of an albumin-inhibited pulmonary surfactant. It was found that dextran could effectively restore surface tension properties of the inhibited surfactant in vitro. Furthermore, dextran improved the performance of pulmonary surfactants when albumin was absent. It was found that when a surfactant film was under high compression (e.g. above 70% surface area reduction), the presence of dextran increased film stability, so that the film could sustain high surface pressures without being collapsing. PMID:12380007

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

    PubMed Central

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

    2015-01-01

    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. PMID:25363329

  16. Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb.

    PubMed

    Ibe, B O; Hibler, S; Raj, J U

    1998-09-01

    Eight near-term fetal lambs were studied acutely in utero to determine role of platelet-activating factor (PAF) in the regulation of vasomotor tone in systemic and pulmonary circulations in the immediate perinatal period. Four fetal lambs were studied predelivery and 2 h postdelivery to determine circulating PAF levels. Aortic and pulmonary arterial pressures and cardiac output were measured continuously, and systemic and pulmonary vascular resistances were calculated. Left pulmonary arterial blood flow was also measured in four fetal lambs. After delivery and oxygenation, circulating PAF levels fell significantly. When WEB-2170, a specific PAF-receptor antagonist, was infused to block effect of endogenous PAF in the eight near-term fetal lambs, systemic vascular resistance fell 30% but pulmonary vascular resistance fell dramatically by 68%. Specificity of WEB-2170 was tested in juvenile lambs and was found to be very specific in lowering vasomotor tone only when tone was elevated by action of PAF. Our data show that endogenous PAF levels in the fetus contribute to maintain a high basal systemic and pulmonary vasomotor tone and that a normal fall in circulating PAF levels after birth and oxygenation may facilitate fall in pulmonary vascular resistance at birth. PMID:9729586

  17. Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α1- and β1-adrenoceptors

    PubMed Central

    Maupoil, V; Bronquard, C; Freslon, J-L; Cosnay, P; Findlay, I

    2007-01-01

    Background and purpose: Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic activity in the pulmonary vein. Experimental approach: Mechanical activity of strips of pulmonary vein isolated from male Wistar rats was recorded via an isometric tension meter. Twitch contractions of cardiac myocytes were evoked by electrical field stimulation in a tissue bath through which flowed Krebs-Heinseleit solution warmed to 36-37°C and gassed with 95% O2 5% CO2. Key results: The superfusion of noradrenaline induced ectopic contractions in 71 of 76 different isolated pulmonary veins. Ectopic contractions in the pulmonary vein were not associated with electrically evoked twitch contractions. The effect of noradrenaline on the pulmonary vein could be replicated by the simultaneous, but not separate, application of the α adrenoceptor agonist phenylephrine and the β adrenoceptor agonist isoprenaline. The use of selective agonists and antagonists for adrenoceptor subtypes showed that ectopic activity in the pulmonary vein arose from the simultaneous stimulation of α1 and β1 adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n=10). Conclusions: These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both α and β adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF. PMID:17325650

  18. Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

    PubMed Central

    Cheung, A K; Parker, C J; Wilcox, L

    1989-01-01

    Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement. PMID:12412765

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

    PubMed

    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

  20. 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

  1. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  2. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  3. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  4. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  5. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  6. Activation Dynamics and Signaling Properties of Notch3 Receptor in the Developing Pulmonary Artery*

    PubMed Central

    Ghosh, Shamik; Paez-Cortez, Jesus R.; Boppidi, Karthik; Vasconcelos, Michelle; Roy, Monideepa; Cardoso, Wellington; Ai, Xingbin; Fine, Alan

    2011-01-01

    Notch3 signaling is fundamental for arterial specification of systemic vascular smooth muscle cells (VSMCs). However, the developmental role and signaling properties of the Notch3 receptor in the mouse pulmonary artery remain unknown. Here, we demonstrate that Notch3 is expressed selectively in pulmonary artery VSMCs, is activated from late fetal to early postnatal life, and is required to maintain the morphological characteristics and smooth muscle gene expression profile of the pulmonary artery after birth. Using a conditional knock-out mouse model, we show that Notch3 receptor activation in VSMCs is Jagged1-dependent. In vitro VSMC lentivirus-mediated Jagged1 knockdown, confocal localization analysis, and co-culture experiments revealed that Notch3 activation is cell-autonomous and occurs through the physical engagement of Notch3 and VSMC-derived Jagged1 in the interior of the same cell. Although the current models of mammalian Notch signaling involve a two-cell system composed of a signal-receiving cell that expresses a Notch receptor on its surface and a neighboring signal-sending cell that provides membrane-bound activating ligand, our data suggest that pulmonary artery VSMC Notch3 activation is cell-autonomous. This unique mechanism of Notch activation may play an important role in the maturation of the pulmonary artery during the transition to air breathing. PMID:21536678

  7. The Role of Activator-Activator Interactions In Reducing in Low-Voltage-Cathodoluminescence Efficiency in Eu and Tb Doped Phosphors

    SciTech Connect

    SEAGER,CARLETON H.; TALLANT,DAVID R.

    1999-12-08

    High resolution measurements of spectrally resolved cathodoluminescence (CL) decay have been made in several commercial and experimental phosphors doped with Eu and Tb at beam energies ranging from 0.8 to 4 keV. CL emission from the lowest two excited states of both rare earth activators was compared to the decay of photoluminescence (PL) after pulsed laser excitation. We find that, at long times after the cessation of electron excitation, the CL decay rates are comparable to those measured in PL, at short times, the decay process is considerably faster and has a noticeable dependence on the energy of the electron beam. These beam energy effects are largest for the higher excited states and for phosphors with larger activator concentrations. Measurements of the experimental phosphors over a range of activator fractions from 0.1 to 0.002 show that the beam energy dependence of the steady-state CL efficiency is larger for higher excited states and weakens as the activator concentration is reduced. The latter effect is strongest for Y{sub 2}SiO{sub 5}:Tb, but also quite evident in Y{sub 2}O{sub 3}:Eu. We suggest that the electron beam dependence of both the decay lifetimes and the steady state CL efficiency may be due to interaction of nearby excited states which occurs as a result of the large energy deposition rate for low energy electrons. This picture-for non-radiative quenching of rare earth emission is an excited state analog of the well-known (ground state-excited state) concentration quenching mechanism.

  8. Photoluminescence, energy transfer and tunable color of Ce(3+), Tb(3+) and Eu(2+) activated oxynitride phosphors with high brightness.

    PubMed

    Lü, Wei; Huo, Jiansheng; Feng, Yang; Zhao, Shuang; You, Hongpeng

    2016-06-21

    New tuneable light-emitting Ca3Al8Si4O17N4:Ce(3+)/Tb(3+)/Eu(2+) oxynitride phosphors with high brightness have been prepared. When doped with trivalent cerium or divalent europium they present blue luminescence under UV excitation. The energy transfer from Ce(3+) to Tb(3+) and Ce(3+) to Eu(2+) ions is deduced from the spectral overlap between Ce(3+) emission and Tb(3+)/Eu(2+) excitation spectra. The energy-transfer efficiencies and corresponding mechanisms are discussed in detail, and the mechanisms of energy transfer from the Ce(3+) to Tb(3+) and Ce(3+) to Eu(2+) ions are demonstrated to be a dipole-quadrupole and dipole-dipole mechanism, respectively, by the Inokuti-Hirayama model. The International Commission on Illumination value of color tuneable emission as well as luminescence quantum yield (23.8-80.6%) can be tuned by controlling the content of Ce(3+), Tb(3+) and Eu(2+). All results suggest that they are suitable for UV light-emitting diode excitation. PMID:27226201

  9. Effects of collagen deposition on passive and active mechanical properties of large pulmonary arteries in hypoxic pulmonary hypertension.

    PubMed

    Wang, Zhijie; Lakes, Roderic S; Eickhoff, Jens C; Chesler, Naomi C

    2013-11-01

    Proximal pulmonary artery (PA) stiffening is a strong predictor of mortality in pulmonary hypertension. Collagen accumulation is mainly responsible for PA stiffening in hypoxia-induced pulmonary hypertension (HPH) in mouse models. We hypothesized that collagen cross-linking and the type I isoform are the main determinants of large PA mechanical changes during HPH, which we tested by exposing mice that resist type I collagen degradation (Col1a1[Formula: see text] and littermate controls (Col1a1[Formula: see text] to hypoxia for 10 days with or without [Formula: see text]-aminopropionitrile (BAPN) treatment to prevent cross-link formation. Static and dynamic mechanical tests were performed on isolated PAs with smooth muscle cells (SMC) in passive and active states. Percentages of type I and III collagen were quantified by histology; total collagen content and cross-linking were measured biochemically. In the SMC passive state, for both genotypes, hypoxia tended to increase PA stiffness and damping capacity, and BAPN treatment limited these increases. These changes were correlated with collagen cross-linking ([Formula: see text]). In the SMC active state, hypoxia increased PA dynamic stiffness and BAPN had no effect in Col1a1[Formula: see text] mice ([Formula: see text]). PA stiffness did not change in Col1a1[Formula: see text] mice. Similarly, damping capacity did not change for either genotype. Type I collagen accumulated more in Col1a1[Formula: see text] mice, whereas type III collagen increased more in Col1a1[Formula: see text] mice during HPH. In summary, PA passive mechanical properties (both static and dynamic) are related to collagen cross-linking. Type I collagen turnover is critical to large PA remodeling during HPH when collagen metabolism is not mutated and type III collagen may serve as a reserve. PMID:23377784

  10. 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. PMID:25278009

  11. 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 ...

  12. Pulmonary hypertension

    MedlinePlus

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

  13. Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

    PubMed Central

    Li, Shaojun; Han, Dong; Zhang, Yonghong; Xie, Xinming; Ke, Rui; Zhu, Yanting; Liu, Lu; Song, Yang; Yang, Lan; Li, Manxiang

    2016-01-01

    Background The current study was performed to investigate the effect of adenosine monophosphate (AMP) – activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms. Material/Methods PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9. Results Activation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression. Conclusions This study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH. PMID:26978596

  14. Circulating Biomarkers of Pulmonary and Extrapulmonary Tuberculosis in Children

    PubMed Central

    Pavan Kumar, Nathella; Anuradha, R.; Andrade, Bruno B.; Suresh, N.; Ganesh, R.; Shankar, Janani; Kumaraswami, V.; Nutman, Thomas B.

    2013-01-01

    Tuberculosis (TB) in children is not only more likely to cause more severe disease than that seen in adults, it is also more likely to be extrapulmonary. Moreover, pediatric TB is very difficult to diagnose and suffers from a lack of understanding of host biomarkers for monitoring the progression of disease. Hence, we sought to identify the expression patterns of a variety of biomarkers in the plasma of children with pulmonary TB (PTB) and extrapulmonary TB (ETB), as well as in healthy control (HC) children. Thus, we examined a variety of circulating markers reflecting tissue inflammation, oxidative stress, innate immune activation, fibrosis, and the cytokine response. Children with active TB, compared to HC children, showed markedly elevated plasma levels of matrix metalloproteinases and their endogenous inhibitors. In addition, children with active TB had significantly elevated levels of C-reactive protein, α-2 macroglobulin, and haptoglobin, as well as hemoxygenase 1. Markers of innate immune activation (lipopolysaccharide [LPS] and lipopolysaccharide-binding protein [LBP]) were significantly lower in ETB than in PTB children. Although there were no significant differences between the two groups in their levels of cytokines (type 1 [gamma interferon (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 2 (IL-2), and IL-12], type 2 [IL-4, IL-5, IL-13, and IL-33], and most type 17 [IL-17A, IL-22, IL-1β, and IL-6] and type 1 interferons [IFN-α and IFN-β]) or most of the cytokines associated with immune modulation (IL-10 and IL-20), pediatric TB was associated with elevated plasma transforming growth factor β (TGF-β), IL-21, and IL-23 levels. Thus, pediatric TB is characterized by elevated levels of a variety of biomarkers at homeostasis, suggesting that these responses may play a crucial role in disease pathogenesis. PMID:23486418

  15. 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

  16. 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 ...

  17. 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. PMID:26853124

  18. Latent cytomegalovirus infection exacerbates experimental pulmonary fibrosis by activating TGF-β1.

    PubMed

    Li, Yonghuai; Gao, Jian; Wang, Guoliang; Fei, Guanghe

    2016-08-01

    The aim of the present study was to investigate the hypotheses that cytomegalovirus (CMV) may trigger idiopathic pulmonary fibrosis (IPF) in a susceptible host and/or that the presence of CMV may alter IPF in response to a well-defined trigger of pulmonary fibrosis. A mouse model of murine CMV (MCMV) infection was established, and the mice were divided into a control group, bleomycin group and an MCMV+bleomycin group. Changes in the weights of the mice were determined in the three groups. Pulmonary fibrosis was detected using a histopathological method. The activity of transforming growth factor (TGF)‑β1 was measured, and the levels of E‑cadherin, Vimentin and phosphorylated (phospho)‑small mothers against decapentaplegic (SMAD)2 were determined using western blot analysis. MCMV was found to invade the lungs, however, it did not cause pulmonary fibrosis. The progression of fibrosis in the mice treated with MCMV+bleomycin was more rapid, compared with that in the control mice. The protein levels of Vimentin and phospho-SMAD2 were upregulated, whereas the level of E‑cadherin was downregulated in the MCMV+bleomycin group,. The results suggested that latent MCMV infection aggravated pulmonary fibrosis in the mouse model, possibly through the activation of TGF-β1. PMID:27279470

  19. Electrical activity of the pulmonary vein and its interaction with the right atrium in the guinea-pig.

    PubMed Central

    Cheung, D W

    1981-01-01

    1. The tunica media of the proximal segments of the pulmonary vein is made up of cardiac muscle cells. The electrical activity of this cardiac portion of the pulmonary vein was studied with intracellular micro-electrodes in isolated preparations. 2. All-or-none action potentials were recorded in all cardiac muscle cells in response to electrical stimulation. These action potentials did not propagate into the adjoining smooth muscle cells. 3. There were differences in properties between cells at the distal end of the cardiac pulmonary vein close to the smooth muscle and those close to the heart. In quiescent preparations, cells at the distal end had resting potentials which averaged 66 mV compared with 71 mV at proximal sites. Action potentials were also smaller and shorter in duration in cells at the distal end. 4. In spontaneously active preparations, pace-making potentials were observed in cells at the distal end while cells close to the heart showed a stable diastolic potential between action potentials. The spontaneous activity of the pulmonary vein was influenced by both inhibitory and excitatory nerves. 5. The interaction between the pulmonary vein and atrial activities was studied in spontaneously active atrial-pulmonary vein preparations. Action potentials recorded from the pulmonary vein always followed those from the right atrium. Electrical stimulation at the pulmonary vein generated action potentials that propagated back into the right atrium. 6. This study demonstrated that isolated pulmonary veins were capable of independent pace-making activity. However the activity of the pulmonary vein was dominated by the SA node in atrial-pulmonary vein preparations under normal conditions. PMID:7310698

  20. 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. PMID:27307558

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Ulinastatin attenuates pulmonary endothelial glycocalyx damage and inhibits endothelial heparanase activity in LPS-induced ARDS.

    PubMed

    Wang, Lipeng; Huang, Xiao; Kong, Guiqing; Xu, Haixiao; Li, Jiankui; Hao, Dong; Wang, Tao; Han, Shasha; Han, Chunlei; Sun, Yeying; Liu, Xiangyong; Wang, Xiaozhi

    2016-09-16

    Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure characterized by major pathologic mechanisms of increased microvascular permeability and inflammation. The glycocalyx lines on the endothelial surface, which determines the vascular permeability, and heparanase play pivotal roles in the degradation of heparan sulfate (HS). HS is the major component of the glycocalyx. The aim of this study is to examine the effects of Ulinastatin (UTI) on vascular permeability and pulmonary endothelial glycocalyx dysfunction induced by lipopolysaccharide (LPS). In our study, C57BL/6 mice and human umbilical vein endothelial cells were stimulated with LPS to induce injury models. After 6 h of LPS stimulation, pulmonary pathological changes, pulmonary edema, and vascular permeability were notably attenuated by UTI. UTI inhibited LPS-induced endothelial glycocalyx destruction and significantly decreased the production of HS as determined by ELISA and immunofluorescence. UTI also reduced the active form of heparanase (50 kDa) expression and heparanase activity. Moreover, lysosome pH was investigated because heparanase (65 kDa) can be reduced easily in its active form at 50 kDa in a low pH environment within lysosome. Results showed that UTI could inhibit LPS-induced pH elevation in lysosome. In conclusion, UTI protects pulmonary endothelial glycocalyx integrity and inhibits heparanase activity during LPS-induced ARDS. PMID:27498004

  7. Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study.

    PubMed

    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

  8. Development of the chronic obstructive pulmonary disease activity rating scale: reliability, validity and factorial structure.

    PubMed

    Morimoto, Michiko; Takai, Kenichi; Nakajima, Kazuo; Kagawa, Koujiro

    2003-03-01

    The purpose of the present study was to develop the Chronic Obstructive Pulmonary Disease (COPD) Activity Rating Scale (CARS) to measure life-related activity in patients with COPD, and to confirm its reliability and constructive validity in a factorial structure model. The subjects consisted of 114 patients with COPD. An 88-item life-related activity list, generated previously from a literature review, was administered. The secondary structural model consisted of four factors with 12 items. The results of the confirmatory factor analysis by structural equation modeling showed the fit criteria to be statistically significant. The internal consistency of the 12 items was highly reliable (Cronbach's alpha = 0.924). The CARS score was correlated with pulmonary function tests, breathlessness, and the health-related quality of life (QOL) scales in Pearson correlation coefficient. The results suggest that the COPD Activity Rating Scale is a valid scale for the assessment of life-related activity in patients with COPD. PMID:12603718

  9. 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

  10. 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. PMID:25990643

  11. 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

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

    SciTech Connect

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

    2014-06-15

    The measurement of the Maxwellian-Averaged Cross-Section (MACS) of the {sup 159}Tb(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. Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension.

    PubMed

    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; Leblanc, Normand

    2012-12-15

    Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca(2+) levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca(2+)-activated Cl- channels (Cl(Ca)), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of Cl(Ca) 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 Ca(2+)-activated Cl(-) current [I(Cl(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 I(Cl(Ca)) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for Cl(Ca) 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 Ca(2+) channel blocker, and NFA (30 or 100 μM, with or without 10 μM indomethacin to inhibit cyclooxygenases) or T16A(Inh)-A01 (10 μM), TMEM16A/Cl(Ca) channel inhibitors, than that of control animals. In conclusion, augmented Cl(Ca)/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

  14. Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

    SciTech Connect

    Jacobs, M.P.; Baughman, R.P.; Hughes, J.; Fernandez-Ulloa, M.

    1985-05-01

    Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (including 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).

  15. 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

  16. 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

  17. Design, Syntheses, and Anti-TB Activity of 1,3-Benzothiazinone Azide and Click Chemistry Products Inspired by BTZ043.

    PubMed

    Tiwari, Rohit; Miller, Patricia A; Chiarelli, Laurent R; Mori, Giorgia; Šarkan, Michal; Centárová, Ivana; Cho, Sanghyun; Mikušová, Katarína; Franzblau, Scott G; Oliver, Allen G; Miller, Marvin J

    2016-03-10

    Electron deficient nitroaromatic compounds such as BTZ043 and its closest congener, PBTZ169, and related agents are a promising new class of anti-TB compounds. Herein we report the design and syntheses of 1,3-benzothiazinone azide (BTZ-N3) and related click chemistry products based on the molecular mode of activation of BTZ043. Our computational docking studies indicate that BTZ-N3 binds in the essentially same pocket as that of BTZ043. Detailed biochemical studies with cell envelope enzyme fractions of Mycobacterium smegmatis combined with our model biochemical reactivity studies with nucleophiles indicated that, in contrast to BTZ043, the azide analogue may have a different mode of activation for anti-TB activity. Subsequent enzymatic studies with recombinant DprE1 from Mtb followed by MIC determination in NTB1 strain of Mtb (harboring Cys387Ser mutation in DprE1 and is BTZ043 resistant) unequivocally indicated that BTZ-N3 is an effective reversible and noncovalent inhibitor of DprE1. PMID:26985313

  18. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

    PubMed Central

    2012-01-01

    Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection. PMID:23272999

  19. 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. PMID:26888428

  20. 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. PMID:26677868

  1. Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers.

    PubMed

    Drath, D B; Do, C; Burd, T; Hong, L L

    1994-03-01

    A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers. PMID:8194852

  2. 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

  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. 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. PMID:27419193

  5. 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. PMID:25490411

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

    PubMed

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

    2015-01-15

    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

  7. 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

  8. Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation

    PubMed Central

    Simarro, Maria; Giannattasio, Giorgio; De la Fuente, Miguel A; Benarafa, Charaf; Subramanian, Kulandayan K.; Ishizawar, Rumey; Balestrieri, Barbara; Andersson, Emma M; Luo, Hongbo R.; Orduña, Antonio; Boyce, Joshua; Anderson, Paul

    2010-01-01

    We have generated Fas activated serine threonine phosphoprotein-deficient mice (FAST−/−) to study the in vivo role of FAST in immune system function. In a model of house dust mite (HDM)-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes and neutrophils. FAST−/− mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in FAST−/− mice compared to wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-α, IL-6 and IL-23) and chemoattractants (MIP-2 and KC) in bronchoalveolar lavage fluids. As FAST−/− neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g. pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a pro-inflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation. PMID:20363972

  9. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis

    PubMed Central

    Ip, Margaret; Chu, Yi Jun; Yung, Irene M. H.; Cheung, Catherine S. K.; Zheng, Lin; Lam, Judy S. Y.; Wong, Ka Tak; Sin, Winnie W. Y.; Choi, Kin Wing; Lee, Nelson

    2016-01-01

    Background We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). Methods A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. Results In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) vs 3.6(3.6–3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001), severity-score (rs +0.317, P = 0.004), and fever and hospitalization durations (rs +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02–1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08–1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2−2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan. Conclusion In patients with active PTB, HMGB1/RAGE

  10. Impact of Educational Intervention on Patients Behavior with Smear-positive Pulmonary Tuberculosis: A Study Using the Health Belief Model

    PubMed Central

    Jadgal, Khair Mohammad; Nakhaei-Moghadam, Tayebeh; Alizadeh-Seiouki, Hadi; Zareban, Iraj; Sharifi-Rad, Javad

    2015-01-01

    Introduction: Tuberculosis is a single-agent infectious disease, which is the major cause of death around the world. Approximately one third of the world’s population is infected with tuberculosis (TB) bacilli and at risk of developing active TB. The purpose of this study was determined the impact of education based on health belief model in promoting behavior of smear-positive pulmonary TB among patients in Chabahar city, Iran. Material and methods: Of the 80 smear-positive pulmonary TB who referred to health centers in Chabahar voluntarily participated in this interventional study. The data collected using questionnaire based on health belief model. The data were analyzed by using paired t-test, independent t-test, pearson correlation and chi-square test with SPSS 16. Results: The cognitive skills were increased significantly from 6.10 to 6.88 after intervention. All behavioral skills were increased significantly from 2.08 to 2.88 after implementing the intervention. Perceived severity was increased from11.08to12.19 significantly. Percepted benefits were enhanced significantly from 11.48 to 12.23. Mean percepted barrier was decreased significantly from 17.52 to 16.68. Conclusion: Findings demonstrated that implementing educational intervention programs can increase the level of knowledge and behavior of patients regarding smear- positive pulmonary TB initiatives. PMID:26543411

  11. Role of thromboxane A₂-activated nonselective cation channels in hypoxic pulmonary vasoconstriction of rat.

    PubMed

    Yoo, Hae Young; Park, Su Jung; Seo, Eun-Young; Park, Kyung Sun; Han, Jung-A; Kim, Kyung Soo; Shin, Dong Hoon; Earm, Yung E; Zhang, Yin-Hua; Kim, Sung Joon

    2012-01-01

    Hypoxia-induced pulmonary vasoconstriction (HPV) is critical for matching of ventilation/perfusion in lungs. Although hypoxic inhibition of K(+) channels has been a leading hypothesis for depolarization of pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, pharmacological inhibition of K(+) channels does not induce significant contraction in rat pulmonary arteries. Because a partial contraction by thromboxane A(2) (TXA(2)) is required for induction of HPV, we hypothesize that TXA(2) receptor (TP) stimulation might activate depolarizing nonselective cation channels (NSCs). Consistently, we found that 5-10 nM U46619, a stable agonist for TP, was indispensible for contraction of rat pulmonary arteries by 4-aminopyridine, a blocker of voltage-gated K(+) channel (K(v)). Whole cell voltage clamp with rat PASMC revealed that U46619 induced a NSC current (I(NSC,TXA2)) with weakly outward rectifying current-voltage relation. I(NSC,TXA2) was blocked by ruthenium red (RR), an antagonist of the transient receptor potential vanilloid-related channel (TRPV) subfamily. 2-Aminoethoxydiphenyl borate, an agonist for TRPV1-3, consistently activated NSC channels in PASMCs. In contrast, agonists for TRPV1 (capsaicin), TRPV3 (camphor), or TRPV4 (α-PDD) rarely induced an increase in the membrane conductance of PASMCs. RT-PCR analysis showed the expression of transcripts for TRPV2 and -4 in rat PASMCs. Finally, it was confirmed that pretreatment with RR largely inhibited HPV in the presence of U46619. The pretreatment with agonists for TRPV1 (capsaicin) and TRPV4 (α-PDD) was ineffective as pretone agents for HPV. Taken together, it is suggested that the concerted effects of I(NSC,TXA2) activation and K(v) inhibition under hypoxia induce membrane depolarization sufficient for HPV. TRPV2 is carefully suggested as the TXA(2)-activated NSC in rat PASMC. PMID:21998141

  12. 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

  13. Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat.

    PubMed

    Yao, Rong; Cao, Yu; He, Ya-rong; Lau, Wayne Bond; Zeng, Zhi; Liang, Zong-an

    2015-01-01

    -dependent manner, via suppression of lung fibroblast activation. Functional AdipoR1 are expressed by human WI-38 lung fibroblasts, suggesting potential future clinical applicability of APN against pulmonary fibrosis. PMID:25945502

  14. Adiponectin Attenuates Lung Fibroblasts Activation and Pulmonary Fibrosis Induced by Paraquat

    PubMed Central

    He, Ya-rong; Lau, Wayne Bond; Zeng, Zhi; Liang, Zong-an

    2015-01-01

    -dependent manner, via suppression of lung fibroblast activation. Functional AdipoR1 are expressed by human WI-38 lung fibroblasts, suggesting potential future clinical applicability of APN against pulmonary fibrosis. PMID:25945502

  15. Influence of structural distortions upon photoluminescence properties of Eu{sup 3+} and Tb{sup 3+} activated Na{sub 3}Ln(BO{sub 3}){sub 2} (Ln=Y, Gd) borates

    SciTech Connect

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

    2012-06-15

    The comparative study of the structure and photoluminescence (PL) properties of the Eu{sup 3+} and Tb{sup 3+} activated Na{sub 3}Ln(BO{sub 3}){sub 2}, with Ln=Y, Gd, showed the important role of the host lattice structure upon PL. Higher emission intensities of Eu{sup 3+} and Tb{sup 3+} are observed for Na{sub 3}Gd(BO{sub 3}){sub 2} than for Na{sub 3}Y(BO{sub 3}){sub 2}, through direct Eu{sup 3+} excitation at 395 nm for Eu{sup 3+} doped borates, and through Gd{sup 3+} excitation around 280 nm for Tb{sup 3+} doped borates. This higher performance for Na{sub 3}Gd(BO{sub 3}){sub 2} is due to the less regular environment of Eu{sup 3+} (Tb{sup 3+}) in the Gd sites than in the Y sites and to energy transfer from Gd{sup 3+} to Eu{sup 3+}(Tb{sup 3+}). The smaller critical concentration in Na{sub 3}Ln{sub 1-x}Tb{sub x}(BO{sub 3}){sub 2} observed for Ln=Gd, x=0.5, compared to x=0.6 for Ln=Y, is explained by shorter Ln-Ln distances (4.11 A for Gd-Gd vs. 4.59 A for Y-Y). Both Na{sub 3}Y{sub 0.4}Tb{sub 0.6}(BO{sub 3}){sub 2} and Na{sub 3}Gd{sub 0.5}Tb{sub 0.5}(BO{sub 3}){sub 2} show intense green emission under UV excitation. - Graphical abstract: The PL properties of Eu{sup 3+} and Tb{sup 3+} are studied in Na{sub 3}Ln(BO{sub 3}){sub 2} (Ln=Y, Gd) borates. Eu{sup 3+} and Tb{sup 3+}exhibits higher emission intensity in Na{sub 3}Gd(BO{sub 3}){sub 2} compared to Na{sub 3}Y(BO{sub 3}){sub 2} due to the less regular environment of the Gd{sup 3+} ion. Energy transfer from Gd{sup 3+} to Tb{sup 3+} is observed. Highlights: Black-Right-Pointing-Pointer Crystal structure of Na{sub 3}Gd(BO{sub 3}){sub 2} by X-ray powder diffraction. Black-Right-Pointing-Pointer Photoluminescence properties of Eu{sup 3+} and Tb{sup 3+} doped Na{sub 3}Ln(BO{sub 3}){sub 2} (Ln=Y, Gd). Black-Right-Pointing-Pointer Higher Eu{sup 3+} and Tb{sup 3+} emission for Na{sub 3}Gd(BO{sub 3}){sub 2} due to an irregular environment of Gd{sup 3+}. Black-Right-Pointing-Pointer Higher Eu{sup 3+} and Tb{sup 3+} emission

  16. 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.

  17. 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

  18. 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…

  19. 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 ...

  20. Elucidating Novel Serum Biomarkers Associated with Pulmonary Tuberculosis Treatment

    PubMed Central

    De Groote, Mary A.; Nahid, Payam; Jarlsberg, Leah; Johnson, John L.; Weiner, Marc; Muzanyi, Grace; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2013-01-01

    In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO) to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Prevention’s Tuberculosis Trials Consortium (TBTC) Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB). We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy. PMID:23637781

  1. A Novel Telomerase Activator Suppresses Lung Damage in a Murine Model of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Le Saux, Claude Jourdan; Davy, Philip; Brampton, Christopher; Ahuja, Seema S.; Fauce, Steven; Shivshankar, Pooja; Nguyen, Hieu; Ramaseshan, Mahesh; Tressler, Robert; Pirot, Zhu; Harley, Calvin B.; Allsopp, Richard

    2013-01-01

    The emergence of diseases associated with telomere dysfunction, including AIDS, aplastic anemia and pulmonary fibrosis, has bolstered interest in telomerase activators. We report identification of a new small molecule activator, GRN510, with activity ex vivo and in vivo. Using a novel mouse model, we tested the potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous mice. Treatment with GRN510 at 10 mg/kg/day activated telomerase 2–4 fold both in hematopoietic progenitors ex vivo and in bone marrow and lung tissue in vivo, respectively. Telomerase activation was countered by co-treatment with Imetelstat (GRN163L), a potent telomerase inhibitor. In this model of bleomycin-induced fibrosis, treatment with GRN510 suppressed the development of fibrosis and accumulation of senescent cells in the lung via a mechanism dependent upon telomerase activation. Treatment of small airway epithelial cells (SAEC) or lung fibroblasts ex vivo with GRN510 revealed telomerase activating and replicative lifespan promoting effects only in the SAEC, suggesting that the mechanism accounting for the protective effects of GRN510 against induced lung fibrosis involves specific types of lung cells. Together, these results support the use of small molecule activators of telomerase in therapies to treat idiopathic pulmonary fibrosis. PMID:23516479

  2. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis.

    PubMed

    Le Saux, Claude Jourdan; Davy, Philip; Brampton, Christopher; Ahuja, Seema S; Fauce, Steven; Shivshankar, Pooja; Nguyen, Hieu; Ramaseshan, Mahesh; Tressler, Robert; Pirot, Zhu; Harley, Calvin B; Allsopp, Richard

    2013-01-01

    The emergence of diseases associated with telomere dysfunction, including AIDS, aplastic anemia and pulmonary fibrosis, has bolstered interest in telomerase activators. We report identification of a new small molecule activator, GRN510, with activity ex vivo and in vivo. Using a novel mouse model, we tested the potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous mice. Treatment with GRN510 at 10 mg/kg/day activated telomerase 2-4 fold both in hematopoietic progenitors ex vivo and in bone marrow and lung tissue in vivo, respectively. Telomerase activation was countered by co-treatment with Imetelstat (GRN163L), a potent telomerase inhibitor. In this model of bleomycin-induced fibrosis, treatment with GRN510 suppressed the development of fibrosis and accumulation of senescent cells in the lung via a mechanism dependent upon telomerase activation. Treatment of small airway epithelial cells (SAEC) or lung fibroblasts ex vivo with GRN510 revealed telomerase activating and replicative lifespan promoting effects only in the SAEC, suggesting that the mechanism accounting for the protective effects of GRN510 against induced lung fibrosis involves specific types of lung cells. Together, these results support the use of small molecule activators of telomerase in therapies to treat idiopathic pulmonary fibrosis. PMID:23516479

  3. MicroRNA-365 in macrophages regulates Mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6.

    PubMed

    Song, Qingzhang; Li, Hui; Shao, Hua; Li, Chunling; Lu, Xiao

    2015-01-01

    The present study is to investigate the relationship between microRNA (miR)-365 expression and the levels of interleukin (IL)-6 mRNA and protein in patients with active tuberculosis. From June 2011 to June 2014, 48 patients with active pulmonary tuberculosis induced by Mycobacterium tuberculosis were included in the study. In addition, 23 healthy subjects were enrolled as control. Macrophages were collected by pulmonary alveolus lavage. In addition, serum and mononuclear cells were isolated from peripheral blood. The levels of miR-365 and IL-6 in macrophages, mononuclear cells and serum were determined using quantitative real-time polymerase chain reaction. The protein expression of IL-6 in macrophages and mononuclear cells was measured using Western blotting, while that in serum was detected by enzyme-linked immunoabsorbent assay. Expression of IL-6 mRNA and protein was significantly enhanced in patients with active pulmonary tuberculosis. Increase of IL-6 protein concentration in serum was probably due to the release of IL-6 protein from mononuclear cells in the blood. In addition, miR-365 levels were significantly lowered in patients with active pulmonary tuberculosis. Up-regulated IL-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of miR-365, suggesting that miR-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via IL-6. PMID:26629035

  4. MicroRNA-365 in macrophages regulates Mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6

    PubMed Central

    Song, Qingzhang; Li, Hui; Shao, Hua; Li, Chunling; Lu, Xiao

    2015-01-01

    The present study is to investigate the relationship between microRNA (miR)-365 expression and the levels of interleukin (IL)-6 mRNA and protein in patients with active tuberculosis. From June 2011 to June 2014, 48 patients with active pulmonary tuberculosis induced by Mycobacterium tuberculosis were included in the study. In addition, 23 healthy subjects were enrolled as control. Macrophages were collected by pulmonary alveolus lavage. In addition, serum and mononuclear cells were isolated from peripheral blood. The levels of miR-365 and IL-6 in macrophages, mononuclear cells and serum were determined using quantitative real-time polymerase chain reaction. The protein expression of IL-6 in macrophages and mononuclear cells was measured using Western blotting, while that in serum was detected by enzyme-linked immunoabsorbent assay. Expression of IL-6 mRNA and protein was significantly enhanced in patients with active pulmonary tuberculosis. Increase of IL-6 protein concentration in serum was probably due to the release of IL-6 protein from mononuclear cells in the blood. In addition, miR-365 levels were significantly lowered in patients with active pulmonary tuberculosis. Up-regulated IL-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of miR-365, suggesting that miR-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via IL-6. PMID:26629035

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

    PubMed

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

    2015-11-01

    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

  6. Possible role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis.

    PubMed

    Kaseda, M; Kadota, J; Mukae, H; Kawamoto, S; Shukuwa, T; Iwashita, T; Matsubara, Y; Ishimatsu, Y; Yoshinaga, M; Abe, K; Kohno, S

    2000-07-01

    A number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation, and selectins together with their ligands are important in the early transient adhesion phase. In this study, we evaluated the role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF) concentrations of soluble (s)L-selectin using an ELISA. Serum and BALF concentrations of sL-selectin were significantly elevated in patients with sarcoidosis compared with control healthy subjects and idiopathic pulmonary fibrosis (IPF) patients (P < 0.05 and P < 0. 01, respectively). The lymphocyte surface marker was also examined in peripheral blood and BALF by flow cytometric analysis. The percentage of CD3+CD62L+ cells (L-selectin-bearing T lymphocytes) was significantly lower in peripheral blood of sarcoidosis than in that of healthy subjects (P < 0.01). In contrast, the percentage of CD3+CD62L- cells (L-selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was significantly higher than in healthy subjects (P < 0.05) and IPF patients (P < 0.01). Furthermore, there was a significant correlation between serum concentrations of sL-selectin and the number of L-selectin-negative T lymphocytes in BALF (r = 0.535, P < 0.01). Our results suggest that L-selectin may be involved in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. PMID:10886252

  7. Possible role of l-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis

    PubMed Central

    Kaseda, M; Kadota, J; Mukae, H; Kawamoto, S; Shukuwa, T; Iwashita, T; Matsubara, Y; Ishimatsu, Y; Yoshinaga, M; Abe, K; Kohno, S

    2000-01-01

    A number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation, and selectins together with their ligands are important in the early transient adhesion phase. In this study, we evaluated the role of l-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF) concentrations of soluble (s)l-selectin using an ELISA. Serum and BALF concentrations of sl-selectin were significantly elevated in patients with sarcoidosis compared with control healthy subjects and idiopathic pulmonary fibrosis (IPF) patients (P < 0·05 and P < 0·01, respectively). The lymphocyte surface marker was also examined in peripheral blood and BALF by flow cytometric analysis. The percentage of CD3+CD62L+ cells (l-selectin-bearing T lymphocytes) was significantly lower in peripheral blood of sarcoidosis than in that of healthy subjects (P < 0·01). In contrast, the percentage of CD3+CD62L− cells (l-selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was significantly higher than in healthy subjects (P < 0·05) and IPF patients (P < 0·01). Furthermore, there was a significant correlation between serum concentrations of sl-selectin and the number of l-selectin-negative T lymphocytes in BALF (r = 0·535, P < 0·01). Our results suggest that l-selectin may be involved in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. PMID:10886252

  8. 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

  9. [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. PMID:19399389

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

    PubMed Central

    Manjaly Thomas, Zita-Rose; McShane, Helen

    2015-01-01

    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. PMID:25636950

  11. Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

    PubMed Central

    2009-01-01

    Background In settings with low background prevalence of tuberculosis (TB) infection, interferon-γ release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON®-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed. Methods From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed. Results Among 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 109/L vs. 8.8 × 109/L; P < 0.001) and a higher median body mass index (22.7 vs. 20.7; P = 0.043) as compared to QFT-G-negative TB patients. Conclusion The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is

  12. 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.

  13. Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity

    PubMed Central

    Schaaf, Bernhard; Liebau, Cornelia; Kurowski, Volkhard; Droemann, Daniel; Dalhoff, Klaus

    2008-01-01

    Background Neutrophil products like matrix metalloproteinases (MMP), involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP). In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S. aureus and pseudomonas species on pulmonary MMPconcentration in human pneumonia. Methods In 37 patients with HAP and 16 controls, MMP-8, MMP-9 and tissue inhibitors of MMP (TIMP) were analysed by ELISA and MMP-9 activity using zymography in bronchoalveolar lavage (BAL). Results MMP-9 activity in mini-BAL was increased in HAP patients versus controls (149 ± 41 vs. 34 ± 11, p < 0.0001). In subgroup analysis, the highest MMP concentrations and activity were seen in patients with high-risk bacteria: patients with high-risk bacteria MMP-9 1168 ± 266 vs. patients with low-risk bacteria 224 ± 119 ng/ml p < 0.0001, MMP-9 gelatinolytic activity 325 ± 106 vs. 67 ± 14, p < 0.0002. In addition, the MMP-8 and MMP-9 concentration was associated with the state of ventilation and systemic inflammatory marker like CRP. Conclusion Pulmonary MMP concentrations and MMP activity are elevated in patients with HAP. This effect is most pronounced in patients with high-risk bacteria. Artificial ventilation may play an additional role in protease activation. PMID:18700005

  14. Stretch-activated channels in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats.

    PubMed

    Ducret, Thomas; El Arrouchi, Jalila; Courtois, Arnaud; Quignard, Jean-François; Marthan, Roger; Savineau, Jean-Pierre

    2010-11-01

    Stretch-activated channels (SACs) act as membrane mechanotransducers since they convert physical forces into biological signals and hence into a cell response. Pulmonary arterial smooth muscle cells (PASMCs) are continuously exposed to mechanical stimulations e.g., compression and stretch, that are enhanced under conditions of pulmonary arterial hypertension (PAH). Using the patch-clamp technique (cell-attached configuration) in PASMCs, we showed that applying graded negative pressures (from 0 to -60 mmHg) to the back end of the patch pipette increases occurrence and activity of SACs. The current-voltage relationship (from -80 to +40 mV) was almost linear with a reversal potential of 1 mV and a slope conductance of 34 pS. SACs were inhibited in the presence of GsMTx-4, a specific SACs blocker. Using microspectrofluorimetry (indo-1), we found that hypotonic-induced cell swelling increases intracellular Ca(2+) concentration ([Ca(2+)](i)). This [Ca(2+)](i) increase was markedly inhibited in the absence of external Ca(2+) or in the presence of the following blockers of SACs: gadolinium, streptomycin, and GsMTx-4. Interestingly, in chronically hypoxic rats, an animal model of PAH, SACs were more active and hypotonic-induced calcium response in PASMCs was significantly higher (nearly a two-fold increase). Moreover, unlike in normoxic rats, intrapulmonary artery rings from hypoxic rats mounted in a Mulvany myograph, exhibited a myogenic tone sensitive to SAC blockers. In conclusion, this work demonstrates that SACs in rat PASMCs can be activated by membrane stretch as well as hypotonic stimulation and are responsible for [Ca(2+)](i) increase. The link between SACs activation-induced calcium response and myogenic tone in chronically hypoxic rats suggests that SACs are an important element for the increased pulmonary vascular tone in PAH and that they may represent a molecular target for PAH treatment. PMID:21035852

  15. VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations.

    PubMed

    Hervé, Virginie; Rabbe, Nathalie; Guilleminault, Laurent; Paul, Flora; Schlick, Laurène; Azzopardi, Nicolas; Duruisseaux, Michael; Fouquenet, Delphine; Montharu, Jérôme; Redini, Françoise; Paintaud, Gilles; Lemarié, Etienne; Cadranel, Jacques; Wislez, Marie; Heuzé-Vourc'h, Nathalie

    2014-01-01

    K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras(LA1) model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations. PMID:25484066

  16. Expression and kinetics of induced procoagulant activity in bovine pulmonary alveolar macrophages.

    PubMed

    Car, B D; Slauson, D O; Suyemoto, M M; Doré, M; Neilsen, N R

    1991-01-01

    Leukocytes, especially macrophages, are important cellular mediators of fibrin deposition and removal at tissue sites of inflammation. Pulmonary fibrin deposition is a prominent feature of bovine acute lung injury; therefore, we studied the resting and stimulated procoagulant responses of bovine pulmonary alveolar macrophages (PAM) and peripheral blood neutrophils (PMN). Freshly isolated normal PAM and PMN expressed negligible procoagulant activity. PAM stimulated with endotoxin lipopolysaccharide (LPS), 4 beta-phorbol 12-myristate 13-acetate (PMA) and bovine recombinant interleukin-1 beta (rBIL-1 beta) exhibited protein synthesis- and dose-dependent enhancement of procoagulant activity in 8-h cultures. Bovine recombinant granulocyte macrophage-colony stimulating factor (rBGM-CSF) and recombinant human gamma-interferon (rHIFN-gamma) did not induce procoagulant activity. The kinetics of LPS- and PMA-enhanced PAM procoagulant activity differed: LPS-induced enhancement developed earlier and more rapidly than PMA-induced enhancement. Pasteurella haemolytica LPS was more potent than Escherichia coli LPS in enhancing PAM procoagulant activity, while dexamethasone decreased both baseline and LPS- or PMA-stimulated activity by approximately 50%. PAM procoagulant activity resulted from tissue factor expression. Bovine PMN produced negligible procoagulant activity when stimulated, and are thus unlikely to be major contributors to procoagulant activity in bovine lung. Activity inhibitory to bovine tissue factor was present in both calf and adult sera, and was partly dependent on the presence of factor X for activity. Rapid induction of bovine PAM procoagulant activity by inflammatory mediators, and subsequent resistance to degradation, may thus combine to promote an alveolar microenvironment permissive to fibrin deposition in bovine acute lung injury. PMID:1959504

  17. Tuberculosis (TB): Treatment

    MedlinePlus

    ... Departments & Divisions Home Conditions Tuberculosis Treating Tuberculosis Treating Tuberculosis Make an Appointment Refer a Patient Ask a ... bones is treated longer. NEXT: Preventive Treatment Diagnosing Tuberculosis History of TB Our Specialists Charles L. Daley, ...

  18. TB Screening Tests

    MedlinePlus

    ... a risk that the first TST is a false-negative reaction, a second skin test is given ... species, for example Mycobacterium kansasii , will give a false-positive TST or IGRA result for TB. Positive ...

  19. Neuromyelitis Optica (NMO) with Abdominal Tuberculosis (TB).

    PubMed

    Bhatty, Shaheen A; Lal, Hari; Talib, Abu; Mahmood, Khalid; Naqvi, Iftekhar; Zaidi, Syeda Shaheera

    2015-10-01

    Neuromyelitis Optica (NMO), previously regarded as a form of multiple sclerosis, is defined by Gault and Devic, as a retrobulbar neuritis or papillitis accompanied by acute myelitis and occasionally other neurological symptom or signs not restricted to the spinal cord or optic nerves. With the diagnosis of specific antibodies, probable role of humoral immunity supports its pathogenesis. Only a few cases of NMO have been reported in association with pulmonary tuberculosis (TB). Here we report a case of young girl with acute onset paraplegia diagnosed to have NMO, who later on during hospital stay developed ascites which cultured positive for Mycobacterium tuberculosis. This association of abdominal TB with NMO is under-reported in literature. PMID:26522188

  20. 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

  1. 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

    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

  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. Haemodynamic response to myocardial ischaemia during unrestricted activity, exercise testing, and atrial pacing assessed by ambulatory pulmonary artery pressure monitoring.

    PubMed

    Levy, R D; Shapiro, L M; Wright, C; Mockus, L; Fox, K M

    1986-07-01

    Ambulatory pulmonary artery pressure monitoring by means of a transducer tipped catheter with a simultaneous frequency modulated electrocardiogram and a miniaturised tape recorder was used to study the haemodynamic implications of ST segment depression in patients with coronary artery disease. Nineteen male patients (mean (SD) age 58 (11) years) with clinical and angiographic evidence of coronary artery disease were studied together with six controls. Changes in the ST segment and pulmonary artery diastolic pressure during treadmill exercise, atrial pacing, and unrestricted ambulant activity were analysed. During exercise, pulmonary artery diastolic pressure rose significantly in patients with coronary artery disease but not in the controls. One patient with ST depression greater than 1 mm did not have a rise in pulmonary artery diastolic pressure on exercise; two had a rise in pulmonary artery diastolic pressure with no ST segment change despite severe angina. The pulmonary artery diastolic pressure tended to rise before or simultaneously with the onset of ST segment depression. The haemodynamic response to atrial pacing was similar in normal controls and patients with coronary artery disease. During ambulatory monitoring there were 29 episodes of ST segment depression all of which were associated with a rise in pulmonary artery diastolic pressure and chest pain. The onset of ST segment depression occurred before a rise in pulmonary artery diastolic pressure in 11 episodes, was simultaneous with it in 11, and followed it in seven episodes. During exercise and ambulatory monitoring there was a correlation between the magnitude of ST segment depression and the rise in pulmonary artery diastolic pressure. Pain was a late feature during exercise, atrial pacing, and anginal episodes. This technique for the first time allows the relation between ST segment changes and haemodynamic alterations in left ventricular function to be assessed in ambulant patients with coronary

  4. Effects of intravenously administered lidocaine on pulmonary vagal afferents and phrenic nerve activity in cats.

    PubMed

    Aoki, M; Harada, Y; Namiki, A; Ikeda, M; Shimizu, H

    1992-10-01

    The ability of lidocaine to suppress activity of single vagal afferent fiber and that of phrenic nerve was studied in 20 cats anesthetized with pentobarbital. Slowly adapting stretch receptors (SAR, n = 16) and rapidly adapting stretch receptors (RAR, n = 7) were identified by their discharge pattern to pulmonary inflation. Intravenous lidocaine (1 mg.kg(-1) or 2 mg.kg(-1)) produced a suppression of SAR activity but not of RAR activity. Suppression of phrenic nerve activity lasted much longer than that of SAR. These findings indicate that iv lidocaine acts more dominantly on CNS than on peripherals. We conclude that iv lidocaine prevents cough and hemodynamic changes caused by airway manipulation mainly through its action on CNS and not on peripherals (peripheral nerves or their receptor). PMID:15278511

  5. 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 ...

  6. 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 ...

  7. 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. PMID:24573542

  8. MEK-ERK Pathway Modulation Ameliorates Pulmonary Fibrosis Associated with Epidermal Growth Factor Receptor Activation

    PubMed Central

    Madala, Satish K.; Schmidt, Stephanie; Davidson, Cynthia; Ikegami, Machiko; Wert, Susan

    2012-01-01

    Pulmonary fibrosis remains a significant public health burden with no proven therapies. The mitogen-activated protein kinase (MAPK)/MAPK kinase (MEK)/extracellular signal–regulated kinase (ERK) signaling cascade is a major pathway controlling cellular processes associated with fibrogenesis, including growth, proliferation, and survival. Activation of the MAPK/ERK pathway is detected in the lungs of human fibrosis samples; however, the effect of modulating the pathway in vivo is unknown. Overexpression of transforming growth factor (TGF)-α in the lung epithelium of transgenic mice causes a progressive pulmonary fibrosis associated with increased MEK/ERK activation localized primarily in mesenchymal cells. To determine the role of the MEK pathway in the induction of TGF-α–induced lung fibrosis, TGF-α was overexpressed for 4 weeks while mice were simultaneously treated with the specific MEK inhibitor, ARRY-142886 (ARRY). Treatment with ARRY prevented increases in lung cell proliferation and total lung collagen, attenuated production of extracellular matrix genes, and protected mice from changes in lung function. ARRY administered as a rescue treatment after fibrosis was already established inhibited fibrosis progression, as assessed by lung histology, changes in body weights, extracellular matrix gene expression, and lung mechanics. These findings demonstrate that MEK inhibition prevents progression of established fibrosis in the TGF-α model, and provides proof of concept of targeting the MEK pathway in fibrotic lung disease. PMID:22021337

  9. Protease activated receptor-1 regulates macrophage-mediated cellular senescence: a risk for idiopathic pulmonary fibrosis

    PubMed Central

    Lin, Cong; Rezaee, Farhad; Waasdorp, Maaike; Shi, Kun; van der Poll, Tom

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a destructive disease in part resulting from premature or mature cellular aging. Protease-activated receptor-1 (PAR-1) recently emerged as a critical component in the context of fibrotic lung diseases. Therefore, we aimed to study the role of macrophages in PAR-1-mediated idiopathic pulmonary fibrosis. The number of macrophages were significantly reduced in lungs of PAR-1 antagonist (P1pal-12) treated animals upon bleomycin instillation. In line with these data, PAR-1 stimulation increased monocyte/macrophage recruitment in response to epithelium injury in in vitro trans-well assays. Moreover, macrophages induced fibroblasts migration, differentiation and secretion of collagen, which were inhibited in the presence of TGF-β receptor inhibitors. Interestingly, these profibrotic effects were partially inhibited by treatment with the PAR-1 inhibitor P1pal-12. Using shRNA mediated PAR-1 knock down in fibroblasts, we demonstrate that fibroblast PAR-1 contributes to TGF-β activation and production. Finally, we show that the macrophage-dependent induction of PAR-1 driven TGF-β activation was mediated by FXa. Our data identify novel mechanisms by which PAR-1 stimulation on different cell types can contribute to IPF and identify macrophages as key players in PAR-1 dependent development of this devastating disease. IPF may result from cellular senescence mediated by macrophages in the lung. PMID:26474459

  10. 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

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

    PubMed

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

    2016-07-01

    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

  12. 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

  13. [Pulmonary rehabilitation].

    PubMed

    Senjyu, Hideaki

    2016-05-01

    Pulmonary rehabilitation commenced in Japan in 1957. However, the development of pulmonary rehabilitation took a long time due to the lack of the necessary health and medical services. Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors. The benefits of pulmonary rehabilitation include a decrease in breathlessness and an improvement in exercise tolerance. It is important that the gains in exercise tolerance lead to an increase in daily physical activity. PMID:27254948

  14. Activation of endothelial and epithelial KCa2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles

    PubMed Central

    Kroigaard, Christel; Dalsgaard, Thomas; Nielsen, Gorm; Laursen, Britt E; Pilegaard, Hans; Köhler, Ralf; Simonsen, Ulf

    2012-01-01

    BACKGROUND AND PURPOSE Small (KCa2) and intermediate (KCa3.1) conductance calcium-activated potassium channels (KCa) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of KCa2.3 and KCa3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries. EXPERIMENTAL APPROACH Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. KCa2 and KCa3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole-cell patch clamp techniques. RESULTS While KCa2.3 expression was similar, KCa3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive KCa2.3 and KCa3.1 proteins were found in both endothelium and epithelium. KCa currents were present in HSAEpi cells and sensitive to the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM-34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the KCa2.3/ KCa3.1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the KCa2 channel blocker apamin, while the KCa3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01–1 µM). CONCLUSIONS AND IMPLICATIONS KCa2.3 and KCa3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. KCa2.3 channels contributed to endo- and epithelium-dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease. PMID:22506557

  15. 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.

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

    PubMed Central

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

    2014-01-01

    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 Ca2+ 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. PMID:25414245

  17. Piloting Upfront Xpert MTB/RIF Testing on Various Specimens under Programmatic Conditions for Diagnosis of TB & DR-TB in Paediatric Population

    PubMed Central

    Raizada, Neeraj; Sachdeva, Kuldeep Singh; Swaminathan, Soumya; Kulsange, Shubhangi; Khaparde, Sunil D.; Nair, Sreenivas Achuthan; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, Mahmud; Sethi, Gulshan Rai; Umadevi, K. R.; Keshav Chander, G.; Saha, Brojakishore; Shah, Amar; Parmar, Malik; Ghediya, Mayank; Jaju, Jyoti; Boehme, Catharina; Paramasivan, Chinnambedu Nainarappan

    2015-01-01

    Background India accounts for one-fifth of the global TB incidence. While the exact burden of childhood TB is not known, TB remains one of the leading causes of childhood mortality in India. Bacteriological confirmation of TB in children is challenging due to difficulty in obtaining quality specimens, in the absence of which diagnosis is largely based on clinical judgement. While testing multiple specimens can potentially contribute to higher proportion of laboratory confirmed paediatric TB cases, lack of high sensitivity tests adds to the diagnostic challenge. We describe here our experiences in piloting upfront Xpert MTB/RIF testing, for diagnosis of TB in paediatric population in respiratory and extra pulmonary specimens, as recently recommended by WHO. Method Xpert MTB/RIF testing was offered to all paediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities in the project areas covering 4 cities of India. Results Under this pilot project, 8,370 paediatric presumptive TB & presumptive DR-TB cases were tested between April and–November 2014. Overall, 9,149 specimens were tested, of which 4,445 (48.6%) were non-sputum specimens. Xpert MTB/RIF gave 9,083 (99.2%, CI 99.0–99.4) valid results. Of the 8,143 presumptive TB cases enrolled, 517 (6.3%, CI 5.8–6.9) were bacteriologically confirmed. TB detection rates were two fold higher with Xpert MTB/RIF as compared to smear microscopy. Further, a total of 60 rifampicin resistant TB cases were detected, of which 38 were detected among 512 presumptive TB cases while 22 were detected amongst 227 presumptive DR-TB cases tested under the project. Conclusion Xpert MTB/RIF with advantages of quick turnaround testing-time, high proportion of interpretable results and feasibility of rapid rollout, substantially improved the diagnosis of bacteriologically confirmed TB in children, while simultaneously detecting rifampicin resistance. PMID:26469691

  18. Australian perspective regarding recommendations for physical activity and exercise rehabilitation in pulmonary arterial hypertension

    PubMed Central

    Fowler, Robin; Jenkins, Sue; Maiorana, Andrew; Gain, Kevin; O’Driscoll, Gerry; Gabbay, Eli

    2011-01-01

    Aim To determine the opinion of health care professionals within Australia, regarding acceptable levels of exertion and symptoms, and referral for exercise rehabilitation in patients with pulmonary arterial hypertension (PAH). Method In 2010, 76 health care professionals at a specialist pulmonary hypertension meeting in Australia were surveyed using a self-administered questionnaire. The questionnaire included case studies of patients with PAH in World Health Organization (WHO) functional classes II–IV. For each case study, respondents were asked to report their opinion regarding the acceptable level of exertion and symptoms during daily activities, and whether they would refer the patient for exercise rehabilitation. Three additional questions asked about advice in relation to four specific physical activities. Results The response rate was 70% (n = 53). Overall, 58% of respondents recommended patients undertake daily activities ‘as tolerated’. There was no consensus regarding acceptable levels of breathlessness or fatigue, but the majority of respondents considered patients should have no chest pain (73%) and no more than mild light-headedness (92%) during daily activities. Overall, 63% of respondents would have referred patients for exercise rehabilitation. There was little difference in opinion regarding the acceptable level of exertion or symptoms, or referral for exercise rehabilitation, according to functional class. However, the patients’ functional class did influence the advice given regarding the specific physical activities. Conclusion In 2010, there were inconsistencies between individual health care professionals within Australia regarding appropriate levels of physical exertion and acceptable symptoms during daily activities. Almost two-thirds of the respondents reported they would refer patients for exercise rehabilitation. PMID:22247620

  19. 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.

  20. Physical Activity and Exertional Desaturation Are Associated with Mortality in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Vainshelboim, Baruch; Kramer, Mordechai Reuven; Izhakian, Shimon; Lima, Ricardo M.; Oliveira, Jose

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA) and exertional desaturation (ED) with mortality in IPF. At baseline, 34 IPF patients (68 (50–81) years) were interviewed using the International Physical Activity Questionnaire (IPAQ), and SpO2 was assessed pre to post 6-min walking test (∆SpO2). Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR) were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS)-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3–71.9), p = 0.027), and ∆SpO2 ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5–365), p = 0.025). This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100–105 min/week were associated with a reduced mortality risk and better survival in IPF. PMID:27548238

  1. Physical Activity and Exertional Desaturation Are Associated with Mortality in Idiopathic Pulmonary Fibrosis.

    PubMed

    Vainshelboim, Baruch; Kramer, Mordechai Reuven; Izhakian, Shimon; Lima, Ricardo M; Oliveira, Jose

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA) and exertional desaturation (ED) with mortality in IPF. At baseline, 34 IPF patients (68 (50-81) years) were interviewed using the International Physical Activity Questionnaire (IPAQ), and SpO₂ was assessed pre to post 6-min walking test (∆SpO₂). Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR) were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS)-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3-71.9), p = 0.027), and ∆SpO₂ ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5-365), p = 0.025). This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100-105 min/week were associated with a reduced mortality risk and better survival in IPF. PMID:27548238

  2. 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.

  3. 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

  4. 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…

  5. 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. PMID:26438324

  6. 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.

  7. Dietary Vitamin D3 Suppresses Pulmonary Immunopathology Associated with Late-Stage Tuberculosis in C3HeB/FeJ Mice.

    PubMed

    Reeme, Allison E; Robinson, Richard T

    2016-02-01

    Tuberculosis (TB) is a significant human disease caused by inhalation of Mycobacterium tuberculosis. Left untreated, TB mortality is associated with a failure to resolve pulmonary immunopathology. There is currently widespread interest in using vitamin D3 (VitD3) as an adjunct therapy for TB because numerous in vitro studies have shown that VitD3 has direct and indirect mycobactericidal activities. However, to date, there have been no in vivo studies addressing whether VitD3 affects experimental TB outcome. In this study, we used C3HeB/FeJ mice to determine whether dietary VitD3 influences the outcome of experimental TB. We observed that although M. tuberculosis burdens did not differ between mice on a VitD3-replete diet (VitD(HI) mice) and mice on a VitD3-deficient diet (VitD(LO) mice), the inflammatory response in VitD(HI) mice was significantly attenuated relative to VitD(LO) controls. Specifically, the expression of multiple inflammatory pathways was reduced in the lungs at later disease stages as were splenocyte IL12/23p40 and IFN-γ levels following ex vivo restimulation. Dietary VitD3 also suppressed the accumulation of T cells in the mediastinal lymph nodes and lung granulomatous regions while concomitantly accelerating the accumulation of F4/80(+) and Ly6C/Ly6G(+) lineages. The altered inflammatory profile of VitD(HI) mice also associated with reductions in pulmonary immunopathology. VitD receptor-deficient (vdr(-/-)) radiation bone marrow chimeras demonstrate that reductions in pulmonary TB immunopathology are dependent on hematopoietic VitD responsiveness. Collectively, our data support a model wherein the in vivo role of VitD3 during TB is not to promote M. tuberculosis killing but rather to function through hematopoietic cells to reduce M. tuberculosis-elicited immunopathology. PMID:26729807

  8. 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.

  9. The Rho kinase inhibitor azaindole-1 has long-acting vasodilator activity in the pulmonary vascular bed of the intact chest rat.

    PubMed

    Pankey, Edward A; Byun, Ryuk J; Smith, William B; Bhartiya, Manish; Bueno, Franklin R; Badejo, Adeleke M; Stasch, Johannes-Peter; Murthy, Subramanyam N; Nossaman, Bobby D; Kadowitz, Philip J

    2012-07-01

    Responses to a selective azaindole-based Rho kinase (ROCK) inhibitor (azaindole-1) were investigated in the rat. Intravenous injections of azaindole-1 (10-300 µg/kg), produced small decreases in pulmonary arterial pressure and larger decreases in systemic arterial pressure without changing cardiac output. Responses to azaindole-1 were slow in onset and long in duration. When baseline pulmonary vascular tone was increased with U46619 or L-NAME, the decreases in pulmonary arterial pressure in response to the ROCK inhibitor were increased. The ROCK inhibitor attenuated the increase in pulmonary arterial pressure in response to ventilatory hypoxia. Azaindole-1 decreased pulmonary and systemic arterial pressures in rats with monocrotaline-induced pulmonary hypertension. These results show that azaindole-1 has significant vasodilator activity in the pulmonary and systemic vascular beds and that responses are larger, slower in onset, and longer in duration when compared with the prototypical agent fasudil. Azaindole-1 reversed hypoxic pulmonary vasoconstriction and decreased pulmonary and systemic arterial pressures in a similar manner in rats with monocrotaline-induced pulmonary hypertension. These data suggest that ROCK is involved in regulating baseline tone in the pulmonary and systemic vascular beds, and that ROCK inhibition will promote vasodilation when tone is increased by diverse stimuli including treatment with monocrotaline. PMID:22591047

  10. 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. PMID:25164319

  11. Factors Associated with Prevalent Tuberculosis Among Patients Receiving Highly Active Antiretroviral Therapy in a Nigerian Tertiary Hospital

    PubMed Central

    Iroezindu, MO; Ofondu, EO; Mbata, GC; van Wyk, B; Hausler, HP; DH, Au; Lynen, L; Hopewell, PC

    2016-01-01

    Background: Tuberculosis (TB) causes significant morbidity/mortality among human immunodeficiency virus-infected individuals in Africa. Reducing TB burden in the era of highly active antiretroviral therapy (HAART) is a public health priority. Aim: We determined the factors associated with prevalent TB among patients receiving HAART. Subjects and Methods: We conducted a cross-sectional study of adult patients who had received HAART for ≥12 weeks in a Nigerian tertiary hospital. Patients whose TB diagnosis predated HAART were excluded from the study. Pre-HAART data were collected from the clinic records, whereas post-HAART data were obtained through medical history, physical examination, and laboratory investigations. Standard TB screening/diagnostic algorithms as applicable in Nigeria were used. Logistic regression analysis was used to determine factors independently associated with prevalent TB. Results: about 65.8% (222/339) were women. The mean age was 41.1 (10.0) years and 23.6% (73/339) had past history of TB. The prevalence of active TB was 7.7% (26/339). Among these patients, 42.3% (11/26) had pulmonary TB, 34.6% (9/26) had disseminated TB, whereas 23.1% (6/26) had only extra-pulmonary disease. Only 45% (9/20) of patients with pulmonary involvement had positive sputum smear. Factors independently associated with prevalent TB were lower social class (adjusted odds ratio [aOR]: 31.7; 95% confidence interval [CI]: 1.1–1417.3), HAART non-adherence (aOR125.5; 95% CI: 9.6–1636.3), baseline CD4 <200cells/μl (aOR31.0; 95%CI: 1.6–590.6), previous TB (aOR13.8; 95% CI: 2.0–94.1), and current hemoglobin <10 g/dl (aOR10.3; 95% CI: 1.1–99.2). Conclusion: Factors associated with prevalent TB were a lower social class, HAART non-adherence, severe immunosuppression before HAART initiation, previous TB, and anemia post-HAART. TB case finding should be intensified in these high-risk groups. PMID:27213096

  12. Activation of the Wnt/Planar Cell Polarity Pathway Is Required for Pericyte Recruitment during Pulmonary Angiogenesis

    PubMed Central

    Yuan, Ke; Orcholski, Mark E.; Panaroni, Cristina; Shuffle, Eric M.; Huang, Ngan F.; Jiang, Xinguo; Tian, Wen; Vladar, Eszter K.; Wang, Lingli; Nicolls, Mark R.; Wu, Joy Y.; de Jesus Perez, Vinicio A.

    2016-01-01

    Pericytes are perivascular cells localized to capillaries that promote vessel maturation, and their absence can contribute to vessel loss. Whether impaired endothelial–pericyte interaction contributes to small vessel loss in pulmonary arterial hypertension (PAH) is unclear. Using 3G5-specific, immunoglobulin G–coated magnetic beads, we isolated pericytes from the lungs of healthy subjects and PAH patients, followed by lineage validation. PAH pericytes seeded with healthy pulmonary microvascular endothelial cells failed to associate with endothelial tubes, resulting in smaller vascular networks compared to those with healthy pericytes. After the demonstration of abnormal polarization toward endothelium via live-imaging and wound-healing studies, we screened PAH pericytes for abnormalities in the Wnt/planar cell polarity (PCP) pathway, which has been shown to regulate cell motility and polarity in the pulmonary vasculature. PAH pericytes had reduced expression of frizzled 7 (Fzd7) and cdc42, genes crucial for Wnt/PCP activation. With simultaneous knockdown of Fzd7 and cdc42 in healthy pericytes in vitro and in a murine model of angiogenesis, motility and polarization toward pulmonary microvascular endothelial cells were reduced, whereas with restoration of both genes in PAH pericytes, endothelial–pericyte association was improved, with larger vascular networks. These studies suggest that the motility and polarity of pericytes during pulmonary angiogenesis are regulated by Wnt/PCP activation, which can be targeted to prevent vessel loss in PAH. PMID:25447046

  13. 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 ...

  14. 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

  15. DFT calculations, spectroscopic, thermal analysis and biological activity of Sm(III) and Tb(III) complexes with 2-aminobenzoic and 2-amino-5-chloro-benzoic acids.

    PubMed

    Essawy, Amr A; Afifi, Manal A; Moustafa, H; El-Medani, S M

    2014-10-15

    The complexes of Sm(III) and Tb(III) with 2-aminobenzoic acid (anthranilic acid, AA) and 2-amino-5-chlorobenzoic acid (5-chloroanthranilic acid, AACl) were synthesized and characterized based on elemental analysis, IR and mass spectroscopy. The data are in accordance with 1:3 [Metal]:[Ligand] ratio. On the basis of the IR analysis, it was found that the metals were coordinated to bidentate anthranilic acid via the ionised oxygen of the carboxylate group and to the nitrogen of amino group. While in 5-chloroanthranilic acid, the metals were coordinated oxidatively to the bidentate carboxylate group without bonding to amino group; accordingly, a chlorine-affected coordination and reactivity-diversity was emphasized. Thermal analyses (TGA) and biological activity of the complexes were also investigated. Density Functional Theory (DFT) calculations at the B3LYP/6-311++G (d,p)_ level of theory have been carried out to investigate the equilibrium geometry of the ligand. The optimized geometry parameters of the complexes were evaluated using SDDALL basis set. Moreover, total energy, energy of HOMO and LUMO and Mullikan atomic charges were calculated. In addition, dipole moment and orientation have been performed and discussed. PMID:24835942

  16. Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals.

    PubMed

    Berghaus, L J; Giguère, S; Sturgill, T L; Bade, D; Malinski, T J; Huang, R

    2012-02-01

    The objectives of this study were to determine the plasma and pulmonary disposition of gamithromycin in foals and to investigate the in vitro activity of the drug against Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Rhodococcus equi. A single dose of gamithromycin (6 mg/kg of body weight) was administered intramuscularly. Concentrations of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection. The minimum inhibitory concentration of gamithromycin required for growth inhibition of 90% of R. equi and S. zooepidemicus isolates (MIC(90)) was determined. Additionally, the activity of gamithromycin against intracellular R. equi was measured. Mean peak gamithromycin concentrations were significantly higher in blood neutrophils (8.35±1.77 μg/mL) and BAL cells (8.91±1.65 μg/mL) compared with PELF (2.15±2.78 μg/mL) and plasma (0.33±0.12 μg/mL). Mean terminal half-lives in neutrophils (78.6 h), BAL cells (70.3 h), and PELF (63.6 h) were significantly longer than those in plasma (39.1 h). The MIC(90) for S. zooepidemicus isolates was 0.125 μg/mL. The MIC of gamithromycin for macrolide-resistant R. equi isolates (MIC(90)=128 μg/mL) was significantly higher than that for macrolide-susceptible isolates (1.0 μg/mL). The activity of gamithromycin against intracellular R. equi was similar to that of azithromycin and erythromycin. Intramuscular administration of gamithromycin at a dosage of 6 mg/kg would maintain PELF concentrations above the MIC(90) for S. zooepidemicus and phagocytic cell concentrations above the MIC(90) for R. equi for approximately 7 days. PMID:21443748

  17. Circulating Myeloid-Derived Suppressor Cells Are Increased and Activated in Pulmonary Hypertension

    PubMed Central

    Nguyen, Cecilia M.; Belchenko, Dmitry D.; Colvin, Kelley L.; Takatsuki, Shinichi; Ivy, D. Dunbar; Stenmark, Kurt R.

    2012-01-01

    Background: Myeloid-derived suppressor cells (MDSCs) are increased in inflammatory and autoimmune disorders and orchestrate immune cell responses therein. Pulmonary hypertension (PH) is associated with inflammation, autoimmunity, and lung vascular remodeling. Immature myeloid cells are found in the lungs of humans and animals with PH, and we hypothesized that they would be increased in the blood of patients with PH compared with control subjects. Methods: Twenty-six children with PH and 10 undergoing cardiac catheterization for arrhythmia ablation were studied. Five milliliters of fresh blood were analyzed using flow cytometry. Results were confirmed using magnetic bead sorting and immunofluorescence, while quantitative polymerase chain reaction and intracellular urea concentration assays were used as measures of MDSC arginase-1 activation. Results: Flow cytometry demonstrated enrichment of circulating MDSCs among patients with PH (n = 26; mean, 0.271 × 106 cells/mL ± 0.17; 1.86% of CD45+ population ± 1.51) compared with control subjects (n = 10; mean, 0.176 × 106 cells/mL ± 0.05; 0.57% of CD45+ population ± 0.29; P < .05). Higher numbers of circulating MDSCs correlated to increasing mean pulmonary artery pressure (r = 0.510, P < .05). Among patients with PH, female patients had a twofold increase in MDSCs compared with male patients. Immunofluorescence analysis confirmed the results of flow cytometry. Quantitative reverse transcription polymerase chain reaction assay results for arginase-1 and measurement of intracellular urea concentration revealed increased activity of MDSCs from patients with PH compared with control subjects. Conclusions: Circulating activated MDSCs are significantly increased in children with PH compared with control subjects. Further investigation of these cells is warranted, and we speculate that they might play significant immunomodulatory roles in the disease pathogenesis of PH. PMID:21940769

  18. Biofunctionalization of CeF3:Tb3+ nanoparticles

    NASA Astrophysics Data System (ADS)

    Kong, D. Y.; Wang, Z. L.; Lin, C. K.; Quan, Z. W.; Li, Y. Y.; Li, C. X.; Lin, J.

    2007-02-01

    CeF3:Tb3+ nanoparticles (short pillar-like morphology with an average length and width of 11 and 5 nm, respectively) were successfully prepared by a polyol process using diethyleneglycol (DEG) as solvent. After being functionalized with a SiO2-NH2 layer, these CeF3:Tb3+ nanoparticles can be conjugated with biotin molecules (activated by thionyl chloride) and further with avidin. The as-formed CeF3:Tb3+ nanoparticles, CeF3:Tb3+ nanoparticles functionalized with amino groups, biotin conjugated amino-functionalized CeF3:Tb3+ nanoparticles and biotinylated CeF3:Tb3+ nanoparticles bonded with avidin were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), UV/vis absorption spectra and luminescence spectra, respectively. The biofunctionalization of the CeF3:Tb3+ nanoparticles has less effect on their luminescence properties, i.e. they still show strong green emission (from Tb3+, with 5D4-7F5 at 543 nm as the most prominent group), indicative of the great potential for these CeF3:Tb3+ nanoparticles to be used as biological fluorescence probes.

  19. Biofunctionalization of CeF(3):Tb(3+) nanoparticles.

    PubMed

    Kong, D Y; Wang, Z L; Lin, C K; Quan, Z W; Li, Y Y; Li, C X; Lin, J

    2007-02-21

    CeF(3):Tb(3+) nanoparticles (short pillar-like morphology with an average length and width of 11 and 5 nm, respectively) were successfully prepared by a polyol process using diethyleneglycol (DEG) as solvent. After being functionalized with a SiO(2)-NH(2) layer, these CeF(3):Tb(3+) nanoparticles can be conjugated with biotin molecules (activated by thionyl chloride) and further with avidin. The as-formed CeF(3):Tb(3+) nanoparticles, CeF(3):Tb(3+) nanoparticles functionalized with amino groups, biotin conjugated amino-functionalized CeF(3):Tb(3+) nanoparticles and biotinylated CeF(3):Tb(3+) nanoparticles bonded with avidin were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), UV/vis absorption spectra and luminescence spectra, respectively. The biofunctionalization of the CeF(3):Tb(3+) nanoparticles has less effect on their luminescence properties, i.e. they still show strong green emission (from Tb(3+), with (5)D(4)-(7)F(5) at 543 nm as the most prominent group), indicative of the great potential for these CeF(3):Tb(3+) nanoparticles to be used as biological fluorescence probes. PMID:21730503

  20. 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

  1. Pulmonary embolus

    MedlinePlus

    ... blood clot; Blood clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... x-ray CT angiogram of the chest Pulmonary ventilation/perfusion scan, also called a V/Q scan ...

  2. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have it, the blood ... heart has to work harder to pump the blood through. Over time, your heart weakens and ... of PH include Shortness of breath during routine activity, such ...

  3. High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants.

    PubMed

    Cederqvist, Katariina; Haglund, Caj; Heikkilä, Päivi; Hollenberg, Morley D; Karikoski, Riitta; Andersson, Sture

    2005-06-01

    Proteinase-activated receptor 2 (PAR(2)), a G-protein-coupled receptor activated by serine proteinases such as trypsin, has been suggested to play an important role in inflammatory and fibroproliferative processes. In preterm infants, the development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation and subsequent interstitial fibrosis. High pulmonary trypsin-2 has been shown to be associated with the development of BPD. We studied the expression and distribution of PAR(2) and trypsin-2 by immunohistochemistry in autopsy lung specimens of fetuses (n = 10), of preterm infants who died of acute or prolonged respiratory distress syndrome (RDS) (n = 8 and n = 7, respectively) or BPD (n = 6), and of newborn infants without lung disease (n = 5) who served as controls. In prolonged RDS and BPD, PAR(2) immunoreactivity was significantly higher in bronchial epithelium when compared with infants without pulmonary pathology (p < 0.05 and p < 0.005, respectively). In alveolar epithelium, expression of PAR(2) was elevated in prolonged RDS when compared with newborn infants without pulmonary pathology (p < 0.05). Moreover, strong expression of PAR(2) was detected in myofibroblasts of thickened and fibrotic alveolar walls in prolonged RDS or BPD. Trypsin-2 was co-localized with PAR(2) in bronchoalveolar epithelium. These findings suggest that PAR(2), possibly activated by trypsin-2, may participate in inflammation and fibroproliferation associated with progression of RDS toward BPD in preterm infants. PMID:15879299

  4. The involvement of platelet activating factor in endotoxin-induced pulmonary platelet recruitment in the guinea-pig.

    PubMed Central

    Beijer, L.; Botting, J.; Crook, P.; Oyekan, A. O.; Page, C. P.; Rylander, R.

    1987-01-01

    1 Exposure of conscious guinea-pigs to an aerosol of endotoxin (25-100 micrograms ml-1) resulted in a dose-related, progressive accumulation of platelets in the thoracic region. Accumulation of 111indium oxine labelled erythrocytes was not observed following exposure to an aerosol of endotoxin (50 micrograms ml-1). 2 Pretreatment of guinea-pigs with the selective platelet activating factor (Paf)-antagonists. CV-3988 or brotizolam resulted in a dose-related inhibition of endotoxin-induced pulmonary platelet recruitment. Pretreatment of guinea-pigs with the selective Paf-antagonist BN 52021 resulted in significant inhibition of endotoxin-induced pulmonary platelet recruitment, although the effects of BN 52021 were not dose-related. 3 Pretreatment of guinea-pigs with indomethacin at doses known to inhibit cyclo-oxygenase did not inhibit endotoxin-induced pulmonary platelet recruitment, whereas higher doses of indomethacin produced a reduction in platelet recruitment in the lung. 4 Pretreatment of guinea-pigs with the anticoagulant heparin and the prostacyclin analogue ZK 36374 inhibited endotoxin-induced platelet recruitment. 5 These observations suggest that endotoxin-induced pulmonary platelet recruitment in the guinea-pig is secondary to the release of platelet activating factor, but not to cyclo-oxygenase products of arachidonic acid and may also involve activation of the coagulation cascade. PMID:2447993

  5. Making a timely diagnosis of pulmonary tuberculosis

    PubMed Central

    Long, Richard

    2015-01-01

    Making a timely diagnosis of adult-type pulmonary tuberculosis (TB) is critical to interrupting transmission and optimizing treatment outcomes. A hypothesis based on clinical experience is that a timely diagnosis may be made by addressing seven clinical rubrics: six related to history, one to the laboratory. Responses may be considered to be part of a clinical heuristic for making a timely diagnosis of pulmonary TB. The larger the number of affirmative responses, the more likely the diagnosis, although it is probable some questions carry more weight than others. The radiograph is key and may almost be considered to be confirmatory of the history. Collectively, the responses should prompt suspicion of pulmonary TB – submission of sputum for acid-fast bacilli smear and culture, and respiratory isolation. PMID:26469154

  6. Endothelin-1 activation of the endothelin B receptor modulates pulmonary endothelial CX3CL1 and contributes to pulmonary angiogenesis in experimental hepatopulmonary syndrome.

    PubMed

    Zhang, Junlan; Yang, Wenli; Hu, Bingqian; Wu, Wei; Fallon, Michael B

    2014-06-01

    Hepatic production and release of endothelin-1 (ET-1) binding to endothelin B (ETB) receptors, overexpressed in the lung microvasculature, is associated with accumulation of pro-angiogenic monocytes and vascular remodeling in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). We have recently found that lung vascular monocyte adhesion and angiogenesis in HPS involve interaction of endothelial C-X3-C motif ligand 1 (CX3CL1) with monocyte CX3C chemokine receptor 1 (CX3CR1), although whether ET-1/ETB receptor activation influences these events is unknown. Our aim was to define if ET-1/ETB receptor activation modulates CX3CL1/CX3CR1 signaling and lung angiogenesis in experimental HPS. A selective ETB receptor antagonist, BQ788, was given for 2 weeks to 1-week CBDL rats. ET-1 (±BQ788) was given to cultured rat pulmonary microvascular endothelial cells overexpressing ETB receptors. BQ788 treatment significantly decreased lung angiogenesis, monocyte accumulation, and CX3CL1 levels after CBDL. ET-1 treatment significantly induced CX3CL1 production in lung microvascular endothelial cells, which was blocked by inhibitors of Ca(2+) and mitogen-activated protein kinase (MEK)/ERK pathways. ET-1-induced ERK activation was Ca(2+) independent. ET-1 administration also increased endothelial tube formation in vitro, which was inhibited by BQ788 or by blocking Ca(2+) and MEK/ERK activation. CX3CR1 neutralizing antibody partially inhibited ET-1 effects on tube formation. These findings identify a novel mechanistic interaction between the ET-1/ETB receptor axis and CX3CL1/CX3CR1 in mediating pulmonary angiogenesis and vascular monocyte accumulation in experimental HPS. PMID:24731444

  7. Tissue Plasminogen Activator Use in Cardiac Arrest Secondary to Fulminant Pulmonary Embolism

    PubMed Central

    Yousuf, Tariq; Brinton, Taylor; Ahmed, Khansa; Iskander, Joy; Woznicka, Daniel; Kramer, Jason; Kopiec, Adam; Chadaga, Amar R.; Ortiz, Kathia

    2016-01-01

    Background Tissue plasminogen activator (tPA) is used emergently to dissolve thrombi in the treatment of fulminant pulmonary embolism. Currently, there is a relative contraindication to tPA in the setting of traumatic or prolonged cardiopulmonary resuscitation > 10 minutes because of the risk of massive hemorrhage. Methods Our single-center, retrospective study investigated patients experiencing cardiac arrest (CA) secondary to pulmonary embolus. We compared the effectiveness of advanced cardiac life support with the administration of tPA vs. the standard of care consisting of advanced cardiac life support without thrombolysis. The primary endpoint was survival to discharge. Secondary endpoints were return of spontaneous circulation (ROSC), major bleeding, and minor bleeding. Results We analyzed 42 patients, of whom 19 received tPA during CA. Patients who received tPA were not associated with a statistically significant increase in survival to discharge (10.5% vs. 8.7%, P = 1.00) or ROSC (47.4% vs. 47.8%, P = 0.98) compared to the control group. We observed no statistically significant difference between the groups in major bleeding events (5.3% in the tPA group vs. 4.3% in the control group, P = 1.00) and minor bleeding events (10.5% in the tPA group vs. 0.0% in the control group, P = 0.11). Conclusion This study did not find a statistically significant difference in survival to discharge or in ROSC in patients treated with tPA during CA compared to patients treated with standard therapy. However, because no significant difference was found in major or minor bleeding, we suggest that the potential therapeutic benefits of this medication should not be limited by the potential for massive hemorrhage. Larger prospective studies are warranted to define the efficacy and safety profile of thrombolytic use in this population. PMID:26858790

  8. Systemic administration of platelet-activating factor in rat reduces specific pulmonary uptake of circulating monoclonal antibody to angiotensin-converting enzyme.

    PubMed

    Atochina, E N; Hiemisch, H H; Muzykantov, V R; Danilov, S M

    1992-01-01

    The biodistribution of radiolabeled mouse monoclonal antibody (MoAb) to angiotensin-converting enzyme (ACE) and control, nonimmune mouse IgG in platelet activating factor (PAF)-treated rats was studied. The blood level of both preparations was slightly decreased (90% of the control) in PAF-treated rats. Specific pulmonary accumulation of anti-ACE MoAb was reduced to 50% of control in contrast to a doubling in nonspecific pulmonary uptake of non-immune IgG. The changes in anti-ACE MoAb biodistribution were lung-specific and were accompanied by decrease in the pulmonary ACE activity (to 60% of control) and increase in serum ACE activity (to 170% of control). Thus anti-ACE MoAb reveals PAF-induced changes in the status of the pulmonary ACE and therefore can be used for the studies of pathology of the pulmonary endothelium. PMID:1331624

  9. 1550 nm VCSEL-based 0.48 Tb/s transmission scheme employing PAM-4 and WDM for active optical cables

    NASA Astrophysics Data System (ADS)

    Markou, S.; Dris, S.; Kalavrouziotis, D.; Avramopoulos, H.; Pleros, N.; Tsiokos, Dimitris M.

    2014-05-01

    With this paper we investigate the system-level performance of VCSELs, parameterized with true experimental LI-VI data and dynamic characteristics of state-of-the-art VCSELs with 3 dB modulation bandwidth at 15 GHz, and propose their deployment as high-speed multi-level optical sources in a mid-range active optical cable (AOC) model for performance prediction of a rack-to-rack interconnection. The AOC architecture combines a 6-element 1550 nm VCSEL array, each directly modulated with 40 Gbaud PAM-4 data, with a wavelength division multiplexer (WDM), in order to implement a parallel link with aggregate traffic of 0.48 Tb/s. Transmission reach exceeded 300 m by deploying a two-tap feed forward equalizer filter at the electrical VCSEL driver. Bit Error Rate (BER) measurements and analysis were carried out in MATLAB. In practice, the thermal behavior and basic operational characteristics of the VCSELs fabricated by the Technische Universität München (TUM) were used to study the thermal performance and operational range of the complete AOC model. The VCSELs were initially operated at 20°C and BER measurements showed power penalties of 1.7 dB and 3.5 dB at 300 m and 500 m of transmission distance respectively for all 6 data channels. System performance was also investigated for elevated operating temperatures of the VCSEL module and the additional system degradation and BER penalties introduced by operation at 50°C and 65°C were also investigated for transmission distances of 300 m and 500 m.

  10. The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis.

    PubMed

    Pekovic-Vaughan, Vanja; Gibbs, Julie; Yoshitane, Hikari; Yang, Nan; Pathiranage, Dharshika; Guo, Baoqiang; Sagami, Aya; Taguchi, Keiko; Bechtold, David; Loudon, Andrew; Yamamoto, Masayuki; Chan, Jefferson; van der Horst, Gijsbertus T J; Fukada, Yoshitaka; Meng, Qing-Jun

    2014-03-15

    The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation upon oxidative stress has been widely investigated, little is known about the endogenous signals that regulate the NRF2 pathway in lung physiology and pathology. Here we show that an E-box-mediated circadian rhythm of NRF2 protein is essential in regulating the rhythmic expression of antioxidant genes involved in glutathione redox homeostasis in the mouse lung. Using an in vivo bleomycin-induced lung fibrosis model, we reveal a clock "gated" pulmonary response to oxidative injury, with a more severe fibrotic effect when bleomycin was applied at a circadian nadir in NRF2 levels. Timed administration of sulforaphane, an NRF2 activator, significantly blocked this phenotype. Moreover, in the lungs of the arrhythmic Clock(Δ19) mice, the levels of NRF2 and the reduced glutathione are constitutively low, associated with increased protein oxidative damage and a spontaneous fibrotic-like pulmonary phenotype. Our findings reveal a pivotal role for the circadian control of the NRF2/glutathione pathway in combating oxidative/fibrotic lung damage, which might prompt new chronotherapeutic strategies for the treatment of human lung diseases, including idiopathic pulmonary fibrosis. PMID:24637114

  11. The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis

    PubMed Central

    Pekovic-Vaughan, Vanja; Gibbs, Julie; Yoshitane, Hikari; Yang, Nan; Pathiranage, Dharshika; Guo, Baoqiang; Sagami, Aya; Taguchi, Keiko; Bechtold, David; Loudon, Andrew; Yamamoto, Masayuki; Chan, Jefferson; van der Horst, Gijsbertus T.J.; Fukada, Yoshitaka; Meng, Qing-Jun

    2014-01-01

    The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation upon oxidative stress has been widely investigated, little is known about the endogenous signals that regulate the NRF2 pathway in lung physiology and pathology. Here we show that an E-box-mediated circadian rhythm of NRF2 protein is essential in regulating the rhythmic expression of antioxidant genes involved in glutathione redox homeostasis in the mouse lung. Using an in vivo bleomycin-induced lung fibrosis model, we reveal a clock “gated” pulmonary response to oxidative injury, with a more severe fibrotic effect when bleomycin was applied at a circadian nadir in NRF2 levels. Timed administration of sulforaphane, an NRF2 activator, significantly blocked this phenotype. Moreover, in the lungs of the arrhythmic ClockΔ19 mice, the levels of NRF2 and the reduced glutathione are constitutively low, associated with increased protein oxidative damage and a spontaneous fibrotic-like pulmonary phenotype. Our findings reveal a pivotal role for the circadian control of the NRF2/glutathione pathway in combating oxidative/fibrotic lung damage, which might prompt new chronotherapeutic strategies for the treatment of human lung diseases, including idiopathic pulmonary fibrosis. PMID:24637114

  12. Contributions of the specialized conduction system to the activation sequence in the canine pulmonary conus.

    PubMed

    Pollard, A E; Spitzer, K W; Burgess, M J

    1997-07-01

    This study was designed to characterize the relative contributions of the specialized conduction system and the myocardial architecture to the ventricular activation sequence. In animal experiments, the activation sequence within a 14 x 14-mm region on each surface of the pulmonary conus from isolated canine hearts was determined from electrograms recorded during ventricular drives applied at the periphery of the measurement region. Recordings were obtained simultaneously from electrode arrays mounted on the endocardium and epicardium. Activation sequences were determined before and after the right ventricular cavity was bathed with a dilute Lugol-normal Tyrode (LNT) solution that selectively inhibited excitation of Purkinje cells. Simulations of action potential propagation in three-dimensional models (14.4 mm long x 7.2 mm wide x 3.6 mm thick) that included the major features of the midwall architecture were performed to aid in the interpretation of the experimental findings. During endocardial pacing (7 animals, 43 total drives), LNT application markedly prolonged the endocardial (13.7 +/- 1.3 ms) and epicardial (5.7 +/- 1.0 ms) activation sequences. However, epicardial isochrone maps constructed with electrograms recorded before LNT application showed no signs of multiple breakthrough sites and, with the exception of overall timing, closely resembled isochrone maps constructed with electrograms recorded after LNT application. During epicardial pacing (9 animals, 55 total drives), LNT application prolonged the endocardial (3.7 +/- 0.6 ms) and epicardial (1.9 +/- 0.6 ms) activation sequences much less dramatically than during endocardial pacing, suggesting a primary contribution of myocardial architecture. However, in those instances where nonuniform anisotropy slowed epicardial expansion of the depolarization wavefront, the specialized conduction system contributed to the activation sequence to a greater extent. PMID:9249520

  13. Reduced Denitration Activity in Peripheral Lung of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Osoata, Grace O.; Ito, Misako; Elliot, Mark; Hogg, James; Barnes, Peter J.

    2012-01-01

    Background Accumulation of nitrated protein is seen in peripheral lung and cells from patients with chronic obstructive pulmonary disease (COPD). Nitrated protein causes abnormal protein function, but the nitration was believed to be an irreversible process. However, there are accumulating evidences that this process is reversible by an active denitration pathway. The aim of this study is to detect denitration activity in protein extracts from peripheral lung tissue of COPD and to compare with those in healthy subjects. Materials and Methods Peripheral lung tissue from 4 healthy, 4 smokers without COPD, 4 GOLD stage 1 and 4 GOLD stage 2 were used for denitration assay. Denitration activity was determined as reduction of nitro-tyrosine level of nitrated histone protein after incubation with protein extracts from peripheral lung, which was determined by western blotting. In addition, RNA is extracted from peripheral lung of 8 healthy, 7 smoking control, 8 stage 1 and 2 COPD and 10 stage 3 and 4 COPD and nitrate reductase mRNA expression was determined by real time RT-PCR. Results Peripheral lung protein extracts from healthy subjects reduced nitro-tyrosine level of nitrated histone. Thus, we were able to show denitration activity in peripheral lungs. The denitration activity was slightly reduced in smoking controls, and significantly reduced in COPD patients. We also showed that the expression of the human homologue of nitrate reductase (chytochrome β2 reductase), a potential candidate of denitrase, was significanty reduced in COPD lung. Conclusion This study suggests that accumulation of nitrated protein in lung tissue of COPD may, at least in part, be induced by a reduction in denitration activity or nitrate reductase. PMID:25191434

  14. Pharmacologic reduction in tumor necrosis factor activity of pulmonary alveolar macrophages.

    PubMed

    Leeper-Woodford, S K; Fisher, B J; Sugerman, H J; Fowler, A A

    1993-02-01

    Tumor necrosis factor-alpha (TNF), an inflammatory cytokine released by macrophages, may be a mediator of lung injury during septicemia. We previously reported that the cyclooxygenase inhibitor ibuprofen and histamine receptor antagonists cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) attenuate lung injury and reduce circulating TNF surges during porcine sepsis. Since pulmonary alveolar macrophages (PAM) may participate in early sepsis by producing TNF, we hypothesized that the TNF activity of PAM is reduced by ibuprofen, cimetidine, and diphenhydramine. To test this, we examined changes in PAM-derived TNF bioactivity and cell viability of freshly isolated porcine PAM during exposure to bacterial endotoxin (LPS), ibuprofen, cimetidine, and diphenhydramine. The TNF activity (% L929 cytotoxicity of PAM conditioned medium) was elevated in LPS-stimulated PAM cultures (15 to 25% increase at 1 to 6 h and 40 to 43% increase at 6 to 48 h, compared with non-LPS-stimulated cultures), and ibuprofen (150 micrograms/ml) added with LPS decreased the TNF activity for 24 h (20 to 28% reduction at 1 to 24 h). Ibuprofen added 1 h after LPS was less effective in reducing the PAM-derived TNF activity (20 to 22% reduction at 2 to 6 h). Cimetidine (112 micrograms/ml) reduced the TNF activity of LPS-stimulated PAM cultures during the first 4 h of LPS exposure (15 to 24% decrease at 1 to 4 h). Diphenhydramine (150 micrograms/ml) attenuated the PAM-derived TNF activity but also decreased viability of PAM, indicating a toxic effect of this agent on PAM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8093999

  15. Pulmonary tuberculosis

    MedlinePlus

    ... unclean living conditions Have poor nutrition The following factors can increase the rate of TB infection in a population: Increase in HIV infections Increase in number of homeless people (poor environment and nutrition) Drug-resistant strains of TB

  16. FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population.

    PubMed

    Lu, Yanjun; Zhu, Yaowu; Wang, Xiong; Wang, Feng; Peng, Jing; Hou, Hongyan; Sun, Ziyong

    2016-02-01

    It is well known that the human innate immune and adaptive immune response play important role in tuberculosis (TB) infection and progress. Emerging evidence shows that FOXO3 plays an important role in the human immune system. Recent research has shown that the FOXO3 genetic variants are associated malaria infection. In this study, 268 confirmed TB patients, 321 patients with latent tuberculosis infection (LTBI), and 475 TB-free controls were recruited; the single-nucleotide polymorphism (SNP) rs12212067: T > G in FOXO3 was genotyped using predesigned TaqMan® allelic discrimination assays. The results showed that the G allele of rs12212067 in FOXO3 was more common in health control and the latent TB group compared with the active TB group (p = 0.048, odds ratio (OR) 95 % confidence intervals (CI) = 1.37 (1.00-1.89); p = 0.042, OR 95 % CI = 1.42 (1.01-1.99), respectively); furthermore, within active TB patients, the G allele of rs12212067 in FOXO3 was more frequent in extra-pulmonary tuberculosis (EPTB) group compared to pulmonary tuberculosis (PTB) group (p = 0.035, OR 95 % CI = 0.57 (0.33-0.97). In conclusion, this study found that rs12212067 in FOXO3 was associated with increased risk of active TB. The minor G allele might be a protection factor which was found more common in latent TB patients and healthy controls than active TB patients. PMID:26223437

  17. 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

  18. 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

  19. The relationship between chitotriosidase activity and tuberculosis.

    PubMed

    Chen, M; Deng, J; Li, W; Su, C; Xia, Y; Wang, M; Li, X; Abuaku, B K; Tan, H; Wen, S W

    2015-11-01

    Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future. PMID:26418349

  20. 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

  1. 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. PMID:24505476

  2. Utility of the Plasma Level of suPAR in Monitoring Risk of Mortality during TB Treatment

    PubMed Central

    Rabna, Paulo; Andersen, Andreas; Wejse, Christian; Oliveira, Ines; Gomes, Victor Francisco; Haaland, Maya Bonde; Aaby, Peter; Eugen-Olsen, Jesper

    2012-01-01

    Objective To investigate whether changes in the plasma level of soluble urokinase plasminogen activator receptor (suPAR) can be used to monitor tuberculosis (TB) treatment efficacy. Design This prospective cohort study included 278 patients diagnosed with active pulmonary TB and followed throughout the 8-month treatment period. Results Mortality during treatment was higher in the highest inclusion quartile of suPAR (23%) compared to the lowest three quartiles (7%), the risk ratio being 3.1 (95% CI 1.65–6.07). No association between early smear conversion and subsequent mortality or inclusion suPAR was observed. After 1 and 2 months of treatment, an increase in suPAR compared to at diagnosis was associated with a Mortality Rate Ratio (MRR) of 4.5 (95%CI: 1.45–14.1) and 2.1 (95%CI 0.62–6.82), respectively, for the remaining treatment period. Conclusions The present study confirmed that elevated suPAR level at time of initiation of TB treatment is associated with increased risk of mortality. Furthermore, increased suPAR levels after one month of treatment was associated with increased risk of mortality during the remaining 7-month treatment period. PMID:22937128

  3. Association of BMI Category Change with TB Treatment Mortality in HIV-Positive Smear-Negative and Extrapulmonary TB Patients in Myanmar and Zimbabwe

    PubMed Central

    Benova, Lenka; Fielding, Katherine; Greig, Jane; Nyang'wa, Bern-Thomas; Casas, Esther Carrillo; da Fonseca, Marcio Silveira; du Cros, Philipp

    2012-01-01

    Objective The HIV epidemic has increased the proportion of patients with smear-negative and extrapulmonary tuberculosis (TB) diagnoses, with related higher rates of poor TB treatment outcomes. Unlike in smear-positive pulmonary TB, no interim markers of TB treatment progress are systematically used to identify individuals most at risk of mortality. The objective of this study was to assess the association of body mass index (BMI) change at 1 month (±15 days) from TB treatment start with mortality among HIV-positive individuals with smear-negative and extrapulmonary TB. Methods and Findings A retrospective cohort study of adult HIV-positive new TB patients in Médecins Sans Frontières (MSF) treatment programmes in Myanmar and Zimbabwe was conducted using Cox proportional hazards regression to estimate the association between BMI category change and mortality. A cohort of 1090 TB patients (605 smear-negative and 485 extrapulmonary) was followed during TB treatment with mortality rate of 28.9 per 100 person-years. In multivariable analyses, remaining severely underweight or moving to a lower BMI category increased mortality (adjusted hazard ratio 4.05, 95% confidence interval 2.77–5.91, p<0.001) compared with remaining in the same or moving to a higher BMI category. Conclusions We found a strong association between BMI category change during the first month of TB treatment and mortality. BMI category change could be used to identify individuals most at risk of mortality during TB treatment among smear-negative and extrapulmonary patients. PMID:22545150

  4. 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

  5. Paradoxical TB-IRIS in HIV-infected adults: a systematic review and meta-analysis.

    PubMed

    Namale, Phiona E; Abdullahi, Leila H; Fine, Stacey; Kamkuemah, Monika; Wilkinson, Robert J; Meintjes, Graeme

    2015-01-01

    Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) was first described almost two decades ago. We undertook this systematic review and meta-analysis to collate findings across studies that have reported the incidence, clinical features, management and outcomes of paradoxical TB-IRIS. Forty studies that cumulatively reported 1048 paradoxical TB-IRIS cases were included. The pooled estimated incidence among patients with HIV-associated TB initiating antiretroviral therapy was 18% (95% CI: 16-21%). Frequent features were pulmonary and lymph node involvement. Hospitalization occurred in 25% (95% CI: 19-30%). In studies that reported treatment, corticosteroids were prescribed more frequently (38%; 95% CI: 27-48%) than nonsteroidal anti-inflammatory drugs (28%; 95% CI: 2-53%). Case fatality was 7% (95% CI: 4-11%), but death attributed to TB-IRIS occurred in 2% of cases (95% CI: 1-3%). PMID:26059627

  6. 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

  7. Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism

    PubMed Central

    Stubblefield, William B.; Alves, Nathan J.; Rondina, Matthew T.; Kline, Jeffrey A.

    2016-01-01

    Background We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)-catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE). Methods Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sex-matched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405). Results Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT. Conclusion The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT. PMID:26866684

  8. Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins

    PubMed Central

    Chen, Yi-Jen; Chen, Yao-Chang; Tai, Ching-Tai; Yeh, Hung-I; Lin, Cheng-I; Chen, Shih-Ann

    2005-01-01

    Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 μM) inhibited the automatic rhythm. Losartan (10 μM) prolonged the AP duration and reduced the contractile force (1 and 10 μM). Angiotensin II reduced the transient outward potassium current (Ito) but increased the L-type calcium, delayed rectifier potassium (IK), transient inward (Iti), pacemaker, and Na+–Ca2+ exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the Ito, IK, Iti, and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation. PMID:16273119

  9. Asymmetric dimethylarginine inhibits HSP90 activity in Pulmonary Arterial Endothelial Cells: Role of Mitochondrial Dysfunction

    PubMed Central

    Sud, Neetu; Wells, Sandra M.; Wiseman, Dean A.; Wilham, Jason; Black, Stephen M.

    2013-01-01

    Increased ADMA levels have been implicated in the pathogenesis of a number of conditions affecting the cardiovascular system. However, the mechanism(s) by which ADMA exerts its effect has not been adequately elucidated. Thus, the purpose of this study was to determine the effect of increased ADMA on nitric oxide (NO) signaling and to begin to elucidate the mechanism by which ADMA acts. Our initial data demonstrated that that ADMA increased NOS uncoupling both in recombinant human endothelial NO synthase (eNOS) and pulmonary arterial endothelial cells (PAEC). Further, we found that this eNOS uncoupling increased 3-nitrotyrosine levels preferentially in the mitochondria of PAEC due to a redistribution of eNOS from the plasma membrane to the mitochondria. This increase in nitration in the mitochondria was found to induce mitochondrial dysfunction as determined by increased mitochondrial derived reactive oxygen species and decreased generation of ATP. Finally, we found that the decrease in ATP resulted in a reduction in the chaperone activity of HSP90 resulting in a decrease in its interaction with eNOS. In conclusion increased levels of ADMA causes mitochondrial dysfunction and a loss of HSP90 chaperone activity secondary to an uncoupling of eNOS. Mitochondrial dysfunction may be an understudied component of the endothelial dysfunction associated with various cardiovascular disease states. PMID:18385287

  10. Targeted delivery of CCR2 antagonist to activated pulmonary endothelium prevents metastasis.

    PubMed

    Roblek, Marko; Calin, Manuela; Schlesinger, Martin; Stan, Daniela; Zeisig, Reiner; Simionescu, Maya; Bendas, Gerd; Borsig, Lubor

    2015-12-28

    Enhanced levels of the inflammatory chemokine CCL2 are known to correlate with increased tumorigenesis and metastases, and thereby poor prognosis for cancer patients. The CCL2-CCR2 chemokine axis was shown to facilitate the metastatic initiation through the recruitment of inflammatory monocytes and the activation of endothelial cells at metastatic sites. Both steps are required for efficient cancer cell trans-endothelial migration and seeding in the targeted tissue. The translation of preclinical evidence proved to be challenging due to systemic effects of chemokine inhibition and limited target specificity. Here we tested an approach of a targeted delivery of the CCR2 antagonist Teijin Compound 1 to metastatic sites. VCAM-1 binding peptide tagged liposomes carrying the CCR2 antagonist enabled a specific delivery to cancer cell-activated endothelium. The subsequent binding of target-sensitive liposomes triggered the release of the Teijin Compound 1 and thereby local inhibition of CCR2 in the lungs. Blocking of CCR2 resulted in reduced induction of the lungs vascular permeability, and thereby reduced tumor cell extravasation. However, the recruitment of inflammatory monocytes to the pre-metastatic lungs remained unaltered. Endothelial VCAM-1 targeted delivery of the CCR2 antagonist resulted in inhibition of pulmonary metastases both in a murine (MC-38GFP cells) and a human xenograft (patient-derived cells) model. Thus, timely- and spatially-defined inhibition of CCR2 signaling represents a potential therapeutic approach for treatment of metastasis without affecting homeostatic functions. PMID:26522070

  11. α-enolase Causes Pro-Inflammatory Activation of Pulmonary Microvascular Endothelial Cells and Primes Neutrophils through Plasmin Activation of Protease-Activated Receptor-2

    PubMed Central

    Bock, Ashley; Tucker, Nicole; Kelher, Marguerite R.; Khan, Samina Y.; Gonzalez, Eduardo; Wohlauer, Max; Hansen, Kirk; Dzieciatkowska, Monika; Sauaia, Angels; Banerjee, Anirban; Moore, Ernest E.; Silliman, Christopher C.

    2015-01-01

    Pro-inflammatory activation of vascular endothelium leading to increased surface expression of adhesion molecules and neutrophil (PMN) sequestration and subsequent activation is paramount in the development of acute lung (ALI) and organ injury in injured patients. We hypothesize that α-enolase, which accumulates in injured patients primes PMNs and causes pro-inflammatory activation of endothelial cells leading to PMN-mediated cytotoxicity. Methods Proteomic analyses of field plasma samples from injured vs. healthy patients was used for protein identification. Human pulmonary microvascular endothelial cells (HMVECs) were incubated with α-enolase or thrombin, and ICAM-1 surface expression was measured by flow cytometry. A two-event in vitro model of PMN cytotoxicity HMVECs activated with α-enolase, thrombin, or buffer was used as targets for lysophosphatidylcholine-primed or buffer-treated PMNs. The PMN priming activity of α-enolase was completed, and lysates from both PMNs and HMVECs were immunoblotted for protease activated receptor-1 (PAR-1) and PAR-2 and co-precipitation of α-enolase with PAR-2 and plasminogen/plasmin. Results α-enolase increased 10.8-fold in injured patients (p<0.05). Thrombin and α-enolase significantly increased ICAM-1 surface expression on HMVECs, which was inhibited by anti-proteases, induced PMN adherence, and served as the first event in the two-event model of PMN cytotoxicity. α-enolase co-precipitated with PAR-2 and plasminogen/plasmin on HMVECs and PMNs and induced PMN priming, which was inhibited by tranexamic acid, and enzymatic activity was not required. We conclude that α-enolase increases post-injury and may activate pulmonary endothelial cells and prime PMNs through plasmin activity and PAR-2 activation. Such pro-inflammatory endothelial activation may predispose to PMN-mediated organ injury. PMID:25944790

  12. Activation of the aryl hydrocarbon receptor increases pulmonary neutrophilia and diminishes host resistance to influenza A virus.

    PubMed

    Teske, Sabine; Bohn, Andrea A; Regal, Jean F; Neumiller, Joshua J; Lawrence, B Paige

    2005-07-01

    Unlike their role in bacterial infection, less is known about the role of neutrophils during pulmonary viral infection. Exposure to pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) results in excess neutrophils in the lungs of mice infected with influenza A virus. TCDD is the most potent agonist for the aryl hydrocarbon receptor (AhR), and exposure to AhR ligands has been correlated with exacerbated inflammatory lung diseases. However, knowledge of the effects of AhR agonists on neutrophils is limited. Likewise, the factors regulating neutrophil responses during respiratory viral infections are not well characterized. To address these knowledge gaps, we determined the in vivo levels of KC, MIP-1alpha, MIP-2, LIX, IL-6, and C5a in infected mouse lungs. Our data show that these neutrophil chemoattractants are generally produced transiently in the lung within 12-24 h of infection. We also report that expression of CD11a, CD11b, CD49d, CD31, and CD38 is increased on pulmonary neutrophils in response to influenza virus. Using AhR-deficient mice, we demonstrate that excess neutrophilia in the lung is mediated by activation of the AhR and that this enhanced neutrophilia correlates directly with decreased survival in TCDD-exposed mice. Although AhR activation results in more neutrophils in the lungs, we show that this is not mediated by deregulation in levels of common neutrophil chemoattractants, expression of adhesion molecules on pulmonary neutrophils, or delayed death of neutrophils. Likewise, exposure to TCDD did not enhance pulmonary neutrophil function. This study provides an important first step in elucidating the mechanisms by which AhR agonists exacerbate pulmonary inflammatory responses. PMID:15792965

  13. Hyperoxia enhanced the production of plasminogen activator by cultured pulmonary artery endothelial cells

    SciTech Connect

    Phillips, P.G.; Ryan, T.J.; Birnby, L.; Tsan, M.F. New York State Health Lab., Albany )

    1990-02-26

    Pulmonary artery endothelial cell (EC) monolayers exposed to hyperoxia show increased permeability to albumin and marked alterations in actin filament distribution. The mechanism for these cytoskeletal changes is unknown. The authors now report that cells exposed to hyperoxia (95% O{sub 2}) produce significant quantities of urokinase-type plasminogen activators (u-PA). Zymographic analysis revealed that plasminogen-dependent caseinolytic activity in conditioned media from O{sub 2}-exposed cells was several fold higher than controls, especially at 48 hr. Cell-associated lytic activity was markedly increased at 48 and 72 hr when oxidative effects on the cytoskeleton were most apparent. Amidolytic assays confirmed these findings. (1) Conditioned media, CTA U/ml (mean {+-} SEM): Control 0.73{+-}0.05 vs 48 hr O{sub 2} 2.09{+-}0.50, (2) Cell-associated activity (preparations enriched for adhesion plaques), CTA mU/10{sup 6} cells: Control 0.17{+-}0.06; O{sub 2}: 24 hr 0.18{+-}0.07; 48 hr 0.46{+-}0.08; 72 hr 0.48{+-}0.08; O{sub 2} 48 hr or 72 hr vs Control. Immunocytochemical analysis demonstrated breakdown and restructuring of fibronectin and collagen components of the extracellular matrix at 48 and 72 hours. They conclude that hyperoxia enhanced both PA production and dismantling of matrix by EC. These changes may in part be responsible for some of the actin filament alterations which occur in conjunction with O{sub 2}-induced permeability increases.

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

    PubMed Central

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

    2014-01-01

    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. PMID:23819753

  15. 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. PMID:26471324

  16. Diagnosing pulmonary tuberculosis with the Xpert MTB/RIF test.

    PubMed

    Bodmer, Thomas; Ströhle, Angelika

    2012-01-01

    Tuberculosis (TB) due to Mycobacterium tuberculosis (MTB) remains a major public health issue: the infection affects up to one third of the world population(1), and almost two million people are killed by TB each year. Universal access to high-quality, patient-centered treatment for all TB patients is emphasized by WHO's Stop TB Strategy. The rapid detection of MTB in respiratory specimens and drug therapy based on reliable drug resistance testing results are a prerequisite for the successful implementation of this strategy. However, in many areas of the world, TB diagnosis still relies on insensitive, poorly standardized sputum microscopy methods. Ineffective TB detection and the emergence and transmission of drug-resistant MTB strains increasingly jeopardize global TB control activities. Effective diagnosis of pulmonary TB requires the availability - on a global scale - of standardized, easy-to-use, and robust diagnostic tools that would allow the direct detection of both the MTB complex and resistance to key antibiotics, such as rifampicin (RIF). The latter result can serve as marker for multidrug-resistant MTB (MDR TB) and has been reported in > 95% of the MDR-TB isolates. The rapid availability of reliable test results is likely to directly translate into sound patient management decisions that, ultimately, will cure the individual patient and break the chain of TB transmission in the community. Cepheid's (Sunnyvale, CA, U.S.A.) Xpert MTB/RIF assay meets the demands outlined above in a remarkable manner. It is a nucleic-acids amplification test for 1) the detection of MTB complex DNA in sputum or concentrated sputum sediments; and 2) the detection of RIF resistance-associated mutations of the rpoB gene. It is designed for use with Cepheid's GeneXpert Dx System that integrates and automates sample processing, nucleic acid amplification, and detection of the target sequences using real-time PCR and reverse transcriptase PCR. The system consists of an instrument

  17. Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis.

    PubMed

    Moreno-Sastre, María; Pastor, Marta; Esquisabel, Amaia; Sans, Eulàlia; Viñas, Miguel; Fleischer, Aarne; Palomino, Esther; Bachiller, Daniel; Pedraz, José Luis

    2016-02-10

    Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most prevalent. As a way to fight against this infection, nanotechnology has emerged over the last decades as a promising alternative to overcome resistance to antibiotics in infectious diseases. The goal of this work was to elaborate and characterize lipid nanoparticles for pulmonary delivery of tobramycin. Tobramycin-loaded nanostructured lipid carriers (Tb-NLCs) were prepared by hot melt homogenization technique. In addition, nanoparticles labeled with infrared dye (IR-NLCs) were used to investigate their in vivo performance after pulmonary administration. Tb-NLCs displayed a mean diameter size around 250 nm, high drug encapsulation (93%) and sustained release profile. Tb-NLCs showed to be active against clinically isolated P. aeruginosa. Moreover, Tb-NLCs did not decrease cell viability and were able to overcome an artificial mucus barrier in the presence of mucolytics agents. During the in vivo assay, IR-NLCs were administered to several mice by the intratracheal route using a Penn Century device. Next, the biodistribution of the nanoparticles was analyzed at different time points showing a wide nanosystem distribution in the lungs. Altogether, tobramycin-loaded NLCs seem to us an encouraging alternative to the currently available CF therapies. PMID:26705155

  18. TB drug development: immunology at the table

    PubMed Central

    Nathan, Carl; Barry, Clifton E.

    2014-01-01

    Summary Our understanding of the host-pathogen relationship in tuberculosis can help guide tuberculosis (TB) drug discovery in at least two ways. First, the recognition that host immunopathology affects lesional TB drug distribution means that pharmacokinetic evaluation of drug candidates needs to move beyond measurements of drug levels in blood, whole lungs or alveolar epithelial lining fluid to include measurements in specific types of lesions. Second, by restricting the replication of M. tuberculosis (Mtb) subpopulations in latent TB infection and in active disease, the host immune response puts Mtb into a state associated with phenotypic tolerance to TB drugs selected for their activity against replicating Mtb. This has spurred a major effort to conduct high throughput screens in vitro for compounds that can kill Mtb when it is replicating slowly if at all. Each condition used in vitro to slow Mtb’s replication and thereby model the phenotypically drug-tolerant state has advantages and disadvantages. Lead candidates emerging from such in vitro studies face daunting challenges in the design of proof-of-concept studies in animal models. Moreover, some non-replicating subpopulations of Mtb fail to resume replication when plated on agar, although their viability is demonstrable by other means. There is as yet no widely replicated assay in which to screen compounds for their ability to kill this ‘viable but non-culturable’ subpopulation. Despite these hurdles, drugs that can kill slowly replicating or non-replicating Mtb may offer our best hope for treatment-shortening combination chemotherapy of TB. PMID:25703568

  19. TB tracer teams in South Africa: knowledge, practices and challenges of tracing TB patients to improve adherence

    PubMed Central

    2013-01-01

    Background In 2008–2009 the South African National Tuberculosis (TB) Program (NTP) implemented a national pilot project, the TB Tracer Project, aiming to decrease default rates and improve patient outcomes. The current study aimed to inform the NTP by describing the knowledge, attitudes, and practices of TB program personnel involved with tracing activities. Methods A self-administered written questionnaire was sent to TB staff, managers and tracer team leaders to assess basic TB knowledge, attitudes and practices. Descriptive statistics were used to summarize results and the chi-squared statistic was used to compare responses of staff at facilities that participated in the TB Tracer Project (tracer) and those that followed standard NTP care (non-tracer). Results Of 560 total questionnaires distributed, 270 were completed and returned (response rate 48%). Total TB knowledge ranged from 70.8-86.3% correct across all response groups. However, just over half (range 50–59.3%) of each respondent group was able to correctly identify the four components of a DOT encounter. A patient no longer feeling sick was cited by 72.1% of respondents as the reason patients fail to adhere to treatment. Tracer teams were viewed as an effective means to get patients to return to treatment by 96.3% of health facility level respondents. Tracer team leaders reported concerns including lack of logistical support (41.7%), insufficient physical safety precautions (41.7%), and inadequate protection from contracting TB (39.1%). Upon patients returning to treatment at the clinic, facilities included in the TB Tracer Project were significantly more likely to discuss alternate DOTS arrangements than non-tracer facilities (79.2 vs. 66.4%, p = 0.03). Conclusions This study identified key components of knowledge, attitudes, and practices regarding TB patient tracing activities in South Africa. Educating patients on the essential need to complete treatment irrespective of clinical symptoms may

  20. Genotypic, Phenotypic and Clinical Validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India

    PubMed Central

    Singh, Urvashi B.; Pandey, Pooja; Mehta, Girija; Bhatnagar, Anuj K.; Mohan, Anant; Goyal, Vinay; Ahuja, Vineet; Ramachandran, Ranjani; Sachdeva, Kuldeep S.; Samantaray, Jyotish C.

    2016-01-01

    Background Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early

  1. Antifungal Activity of the Pradimicin Derivative BMS 181184 in the Treatment of Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits

    PubMed Central

    Gonzalez, Corina E.; Groll, Andreas H.; Giri, Neelam; Shetty, Daiva; Al-Mohsen, Ibrahim; Sein, Tin; Feuerstein, Erwin; Bacher, John; Piscitelli, Stephen; Walsh, Thomas J.

    1998-01-01

    The activity of the pradimicin derivative BMS 181184 was evaluated in a model of invasive pulmonary aspergillosis in persistently neutropenic rabbits and compared with that of amphotericin B deoxycholate. BMS 181184 at total daily doses of 50 and 150 mg/kg of body weight was at least as effective as amphotericin B at 1 mg/kg once a day in conferring survival and had comparable activity in reducing organism-mediated tissue injury and excess lung weight. Although treatment at all dosing regimens of BMS 181184 resulted in significant reductions in fungal tissue burden compared to untreated controls, equivalence to amphotericin B occurred only at the higher dosage level. Similar observations were made in bronchoalveolar lavage fluid cultures obtained postmortem. Monitoring of the animals through ultrafast computerized tomography scan revealed a marked resolution of pulmonary lesions during treatment with BMS 181184. The compound was well tolerated at all dosing regimens, and no toxicity was noted. Pharmacokinetic studies revealed nonlinear drug disposition with increased clearance at higher dosages and some evidence for extravascular drug accumulation. BMS 181184 had excellent activity in the treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits, thus underscoring the potential of pradimicin derivatives in therapy of invasive aspergillosis in the neutropenic host. PMID:9736570

  2. 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

  3. 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 ...

  4. Pulmonary embolus

    MedlinePlus

    ... Blood clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... area). This type of clot is called a deep vein thrombosis (DVT) . The blood clot breaks off and travels ...

  5. 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.

  6. Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis ▿

    PubMed Central

    Khan, Nooruddin; Alam, Kaiser; Nair, Shiny; Valluri, Vijaya Lakshmi; Murthy, Kolluri J. R.; Mukhopadhyay, Sangita

    2008-01-01

    Accurate diagnosis of tuberculosis (TB) infection is critical for the treatment, prevention, and control of TB. Conventional diagnostic tests based on purified protein derivative (PPD) do not achieve the required diagnostic sensitivity. Therefore, in this study, we have evaluated the immunogenic properties of Rv1168c, a member of the PPE family, in comparison with PPD, which is routinely used in the tuberculin test, and Hsp60 and ESAT-6, well-known immunodominant antigens of Mycobacterium tuberculosis. In a conventional enzyme immunoassay, the recombinant Rv1168c protein displayed stronger immunoreactivity against the sera obtained from patients with clinically active TB than did PPD, Hsp60, or ESAT-6 and could distinguish TB patients from Mycobacterium bovis BCG-vaccinated controls. Interestingly, Rv1168c antigen permits diagnosis of smear-negative pulmonary TB as well as extrapulmonary TB cases, which are often difficult to diagnose by conventional tests. The immunodominant nature of Rv1168c makes it a promising candidate to use in serodiagnosis of TB. In addition, our studies also show that Rv1168c is a potent T-cell antigen which elicits a strong gamma interferon response in sensitized peripheral blood mononuclear cells obtained from TB patients. PMID:18400969

  7. TB control: challenges and opportunities for India.

    PubMed

    Pai, Madhukar; Daftary, Amrita; Satyanarayana, Srinath

    2016-03-01

    India's TB control programme has treated over 19 million patients, but the incidence of TB continues to be high. TB is a major killer and drug-resistant TB is a growing threat. There are several likely reasons, including social conditions and co-morbidities that fuel the TB epidemic: under-investment by the government, weak programme implementation and management, suboptimal quality of care in the private sector, and insufficient advocacy around TB. Fortunately, India possesses the technical know-how, competence and resources to address these challenges. The End TB Strategy by WHO offers India an excellent blueprint to advance the agenda of TB control. PMID:26884494

  8. Activity of endothelium-derived hyperpolarizing factor is augmented in monocrotaline-induced pulmonary hypertension of rat lungs.

    PubMed

    Morio, Yoshiteru; Homma, Noriyuki; Takahashi, Hideki; Yamamoto, Akihito; Nagaoka, Tetsutaro; Sato, Koichi; Muramatsu, Masashi; Fukuchi, Yoshinosuke

    2007-01-01

    The mechanism of endothelium-dependent vasodilator signaling involves three components such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Although EDHF is distinct from nitric oxide and prostacyclin, it requires activation of Ca(2+)-sensitive K(+) channels (K(Ca)) and cytochrome P(450) metabolites. However, the physiological role of EDHF in the pulmonary circulation is unclear. Thus, we tested if EDHF would regulate vascular tone in rat lungs of control and monocrotaline (MCT)-induced pulmonary hypertension. Inhibition of EDHF with a combination of K(Ca) blockers, charybdotoxin (50 nM) plus apamin (50 nM), increased baseline vascular tone in MCT-induced hypertensive lungs. Thapsigargin (TG; 100 nM), an inhibitor of Ca-ATPase, caused greater EDHF-mediated vasodilation in MCT-induced hypertensive lungs. TG-induced vasodilation was abolished with the charybdotoxin-apamin combination. Sulfaphenazole (10 muM), a cytochrome P(450) inhibitor, reduced the TG-induced vasodilation in MCT-induced hypertensive lungs. RT-PCR analysis exhibited an increase in K(Ca) mRNA in MCT-treated lungs. These results indicate the augmentation of tonic EDHF activity, at least in part, through the alteration in cytochrome P(450) metabolites and the upregulation of K(Ca) expression in MCT-induced pulmonary hypertension. PMID:17438361

  9. Effects of carbon dioxide level (PCO sub 2 ) on the fibrinolytic activity (FA) of pulmonary artery endothelial cells (PAEC)

    SciTech Connect

    Langleben, D.; Moroz, L.A.; Danes, D. )

    1990-02-26

    Recovery from pulmonary thromboembolism depends on the rapidity and completeness of clot lysis. This involves endogenous fibrinolytic mechanisms, particularly the balance between plasminogen activators and inhibitors produced by endothelial cells. Hypocapnia is common in pulmonary embolism, however it is not known if endothelial fibrinolytic function is affected by PCO{sub 2}. The authors therefore measured the FA in medium (MCDB-131, 0.5% albumin) conditioned for 20 hours in-vitro by exposure to confluent cultures of bovine proximal PAEC. During conditioning, cells were exposed to 5% CO{sub 2} in air (PCO{sub 2} - 36-40mm Hg, CONTROL), or various PCO{sub 2} levels (30-55 mmHg, in air). FA of conditioned medium was determined by {sup 125}I-fibrin solid phase assay, with addition of plasminogen (10 ug/ml). With PCO{sub 2} levels {le} 35 mmHg, FA in the conditioned medium was 5 to 18% higher than CONTROL FA. When PCO{sub 2} was {ge} 45 mmHg, FA decreased 5 to 60% as compared to CONTROL FA. There was a significant negative linear relationship between PCO{sub 2} and FA. Thus, PCO{sub 2} level can affect PAEC mediated plasminogen activation. This finding may be relevant to in-vivo clearance of clots from pulmonary arteries.

  10. 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

    2016-09-01

    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. PMID:27298272

  11. Platelet-activating factor induces selective pulmonary arterial hyperreactivity in isolated perfused rabbit lungs.

    PubMed

    Ohar, J A; Waller, K S; Dahms, T E

    1993-07-01

    The role of vasoreactivity in PAF-induced pulmonary hypertension (PHT) was assessed in isolated, perfused rabbit lungs. We evaluated the steady-state pulmonary vascular response to five vasoconstrictors: PGF2 alpha, norepinephrine, angiotensin II, PAF, and KCl. Pulmonary arterial pressure and pulmonary vascular resistance (PVR) were significantly greater in lungs of rabbits treated with PAF for 28 days than in control rabbits in response to PGF2 alpha and norepinephrine. When resistance was partitioned by the vascular occlusion method, at baseline the vascular resistance was equally distributed between arterial and venous segments in both experimental groups. Arterial resistance accounted for approximately 76% of PVR during norepinephrine injection and 60% of PVR during PGF2 alpha injection in PAF-treated lungs. Whereas arterial resistance accounted for approximately 63% of PVR during norepinephrine injection and 52% of PVR during PGF2 alpha injection in control lungs, there was no significant difference in the response to angiotensin II, acute PAF, and KCl in lungs from chronic PAF-treated rabbits compared with responses in control rabbit lungs, though the pressor response to acute PAF tended to be blunted in PAF-treated lungs. Chronic PAF treatment results in enhanced pulmonary arterial reactivity to selected autacoids in isolated perfused lungs. PMID:8317792

  12. Effect of platelet activating factor (PAF) on pulmonary circulation in isolated rabbit lung.

    PubMed

    Comellas, A; Tristano, S; Pesce, L; Friedman, E; Marcano, H; Sánchez de León, R

    1999-03-01

    Platelet activating factor (PAF) has been implicated in the pathophysiology of acute lung injury. The aim of this work is to study the effect of PAF on isolated and perfused rabbit lungs with blood and with a blood-free solution. 24 isolated and perfused rabbit lungs have been used: 8 control preparations (CP), 4 vehicles preparations (VP), 8 PAF preparations (PP) to which we administered PAF (1 microg/Kg of rabbit weight) and 4 acellular preparations (AP) with the same dose of PAF as in PP but dissolved in BSA-Krebs buffer solution. In the preparations pulmonary artery pressure (Ppa), airway pressure (Paw), left atria pressure (Pla) and fluid filtration rate (FFR) were registered. Ppa resulted in a significant difference in AP vs PP, with a value of 21 cm of water (CI 95%: 12-26) vs 205.1 cm of water (CI 95%: 141.3 - 271) respectively. A increase in FFR was observed in PP but it did not occur in AP, the difference being statistically significant: 5.515 g/min (CI 95 %: 2.425 - 8.865) vs 0.049 g/min (CI 95%: 0.008 - 0.32) respectively. Paw was statistically different in PP vs AP, with a value of 14.3 cm of water (CI 95%: 11.57 - 16.7) vs 8.5 cm of water (CI 95%: 8-9) respectively. These results suggest that PAF does not have a direct effect on the endothelium or smooth muscle in the production of lung edema. PMID:10494654

  13. Pulmonary gas exchange is not impaired 24 h after extravehicular activity.

    PubMed

    Prisk, G Kim; Fine, Janelle M; Cooper, Trevor K; West, John B

    2005-12-01

    Extravehicular activity (EVA) during spaceflight involves a significant decompression stress. Previous studies have shown an increase in the inhomogeneity of ventilation-perfusion ratio (VA/Q) after some underwater dives, presumably through the embolic effects of venous gas microemboli in the lung. Ground-based chamber studies simulating EVA have shown that venous gas microemboli occur in a large percentage of the subjects undergoing decompression, despite the use of prebreathe protocols to reduce dissolved N(2) in the tissues. We studied eight crewmembers (7 male, 1 female) of the International Space Station who performed 15 EVAs (initial cabin pressure 748 mmHg, final suit pressure either approximately 295 or approximately 220 mmHg depending on the suit used) and who followed the denitrogenation procedures approved for EVA from the International Space Station. The intrabreath VA/Q slope was calculated from the alveolar Po(2) and Pco(2) in a prolonged exhalation maneuver on the day after EVA and compared with measurements made in microgravity on days well separated from the EVA. There were no significant changes in intrabreath VA/Q slope as a result of EVA, although there was a slight increase in metabolic rate and ventilation (approximately 9%) on the day after EVA. Vital capacity and other measures of pulmonary function were largely unaltered by EVA. Because measurements could only be performed on the day after EVA because of logistical constraints, we were unable to determine an acute effect of EVA on VA/Q inequality. The results suggest that current denitrogenation protocols do not result in any major lasting alteration to gas exchange in the lung. PMID:16123205

  14. Influence of the polymorphism of the DUSP14 gene on the expression of immune-related genes and development of pulmonary tuberculosis.

    PubMed

    Hijikata, M; Matsushita, I; Le Hang, N T; Thuong, P H; Tam, D B; Maeda, S; Sakurada, S; Cuong, V C; Lien, L T; Keicho, N

    2016-06-01

    Recently, a genome-wide screening identified a functional single-nucleotide polymorphism in dual-specificity phosphatase 14 gene (DUSP14), which was associated with pulmonary tuberculosis (TB) in a West African study. DUSP14 regulates T-cell proliferation and cytokine production in a negative way via dephosphorylation and inactivation of key signaling molecules. The aim of this study is to further explore the possible significance of the DUSP14 polymorphism. Total RNA was extracted from the whole blood of 109 healthcare workers (HCWs) in Vietnam and subjected to quantitative reverse-transcription PCR for DUSP14 and 20 immune-related genes. DUSP14 rs1051838 was genotyped in 502 new pulmonary TB patients and 506 healthy controls. Among disease-free individuals (HCWs), T-helper type-1 (Th1)-related genes, interferon-gamma receptor 2 (IFNGR2) and signal transducer and activator of transcription-1 (STAT1) mRNA levels significantly increased as the number of A alleles of rs1051838 increased, whereas the DUSP14 mRNA level tended to decrease. The AA genotype was associated with protection against active TB in younger patients (⩽45 years old, OR=0.63, 95% CI 0.44-0.90). Our results suggest that a low-expression genotype of DUSP14 accompanied by high transcript levels of Th1 immune-related genes may confer protection against early TB development. PMID:26938665

  15. Imaging Features of Pulmonary CT in Type 2 Diabetic Patients with Multidrug-Resistant Tuberculosis

    PubMed Central

    Jiang, Hongbo; Ren, Yanwei; Lu, Xiwei

    2016-01-01

    Background Until now, radiographic manifestations of multidrug-resistant pulmonary tuberculosis (MDR- TB) in patients with diabetes mellitus (DM) have not been reported. We conducted a study to investigate the imaging features of pulmonary computed tomography (CT) for type 2 diabetic (T2DM) patients with MDR-TB. Methods The clinical data and pulmonary CT findings of 39 type 2 diabetic patients with MDR-TB, 46 type 2 diabetic patients with drug-susceptible tuberculosis (DS-TB), and 72 pure drug-susceptible TB cases (without T2DM and MDR) treated at Dalian Tuberculosis Hospital from 2012 to 2015 were collected, and the clinical features and imaging differences of the three groups were compared. Results The clinical characteristics of the three groups of patients were not significantly different except with respect to age and previous treatment history. However, on imaging, the patients with MDR-TB showed consolidation in and above the pulmonary segments was significantly more extensive than that seen in the DS-TB group with or without T2DM. Conclusion Consolidation in or above multiple pulmonary segments with multiple mouth-eaten cavities and bronchial damage on pulmonary CT images in type 2 diabetic patients with tuberculosis suggests the possibility of multi-drug resistance. PMID:27022735

  16. Pulmonary valve stenosis

    MedlinePlus

    ... valve pulmonary stenosis; Pulmonary stenosis; Stenosis - pulmonary valve; Balloon valvuloplasty - pulmonary ... water pills) Treat abnormal heartbeats and rhythms Percutaneous balloon pulmonary dilation (valvuloplasty) may be performed when no ...

  17. Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

    PubMed Central

    Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; Mc Neeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Oramasionwu, Gloria E; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H. Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

    2015-01-01

    Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle. PMID:25957923

  18. LPS-mediated endothelial activation in pulmonary endothelial cells: role of Nox2-dependent IKK-β phosphorylation

    PubMed Central

    Menden, Heather; Tate, Everett; Hogg, Neil

    2013-01-01

    Lipopolysaccharide (LPS)-mediated endothelial activation contributes to lung inflammation and alveolar remodeling seen in premature infants with bronchopulmonary dysplasia (BPD). The mechanisms underlying LPS-mediated oxidative stress and proinflammatory signaling in human pulmonary microvascular endothelial cells (HPMEC) remain unclear. We hypothesized that NADPH oxidase (Nox) mediates LPS-induced endothelial activation in HPMEC by regulating phosphorylation of Toll-like receptor (TLR) pathway proteins. LPS-induced expression of intercellular adhesion molecule 1 (ICAM-1) was associated with increased 2-OH-E+ (marker for superoxide formation) levels and was attenuated by apocynin and the Nox inhibitor, VAS2870. LPS triggered membrane translocation of p67phox, suggesting activation of Nox2. Silencing Nox2, but not Nox4, suppressed LPS-induced ICAM-1 expression in HPMEC. Immunoprecipitation studies showed that inhibitor of κ-B kinase-β (IKK-β) serine phosphorylation induced by LPS was inhibited by Nox2 silencing. We examined whether Nox2-dependent, LPS-mediated IKK-β phosphorylation was regulated by protein phosphatase 2A (PP2A) or TGF-β associated kinase-1 (TAK1) in HPMEC. LPS increased PP2A activity in HPMEC, and inhibition of PP2A did not alter LPS-mediated ICAM-1 expression but attenuated IKK-β phosphorylation. TAK1 inhibition decreased LPS-induced ICAM-1 expression in HPMEC, and Nox2 silencing attenuated LPS-mediated TAK1 phosphorylation (Thr184/187). We demonstrate that Nox2 regulates LPS-mediated endothelial activation in pulmonary endothelial cells by modulating phosphorylation of key kinases in the TLR signaling cascade. Our data support a novel mechanism by which Nox-dependent signaling regulates proinflammatory signaling in pulmonary endothelial cells. Inhibition of vascular Nox may potentially limit lung injury and alveolar remodeling caused by infections in BPD. PMID:23333803

  19. Tricks to translating TB transcriptomics.

    PubMed

    Deffur, Armin; Wilkinson, Robert J; Coussens, Anna K

    2015-05-01

    Transcriptomics and other high-throughput methods are increasingly applied to questions relating to tuberculosis (TB) pathogenesis. Whole blood transcriptomics has repeatedly been applied to define correlates of TB risk and has produced new insight into the late stage of disease pathogenesis. In a novel approach, authors of a recently published study in Science Translational Medicine applied complex data analysis of existing TB transcriptomic datasets, and in vitro models, in an attempt to identify correlates of protection in TB, which are crucially required for the development of novel TB diagnostics and therapeutics to halt this global epidemic. Utilizing latent TB infection (LTBI) as a surrogate of protection, they identified IL-32 as a mediator of interferon gamma (IFNγ)-vitamin D dependent antimicrobial immunity and a marker of LTBI. Here, we provide a review of all TB whole-blood transcriptomic studies to date in the context of identifying correlates of protection, discuss potential pitfalls of combining complex analyses originating from such studies, the importance of detailed metadata to interpret differential patient classification algorithms, the effect of differing circulating cell populations between patient groups on the interpretation of resulting biomarkers and we decipher weighted gene co-expression network analysis (WGCNA), a recently developed systems biology tool which holds promise of identifying novel pathway interactions in disease pathogenesis. In conclusion, we propose the development of an integrated OMICS platform and open access to detailed metadata, in order for the TB research community to leverage the vast array of OMICS data being generated with the aim of unraveling the holy grail of TB research: correlates of protection. PMID:26046091

  20. 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

  1. 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

  2. Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase activator, BAY 60–2770, are not dependent on endogenous nitric oxide or reduced heme

    PubMed Central

    Pankey, Edward A.; Bhartiya, Manish; Badejo, Adeleke M.; Haider, Umair; Stasch, Johannes-Peter; Murthy, Subramanyam N.; Nossaman, Bobby D.

    2011-01-01

    4-({(4-Carboxybutyl)[2-(5-fluoro-2-{[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}methyl)benzoic acid (BAY 60–2770) is a nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC) that increases the catalytic activity of the heme-oxidized or heme-free form of the enzyme. In this study, responses to intravenous injections of the sGC activator BAY 60–2770 were investigated under baseline and elevated tone conditions induced by the thromboxane mimic U-46619 when NO synthesis was inhibited by Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME), when sGC activity was inhibited by 1H-[1,2,4]-oxadizaolo[4,3]quinoxaline-1-one (ODQ), an agent that oxidizes sGC, and in animals with monocrotaline-induced pulmonary hypertension. The intravenous injections of BAY 60–2770 under baseline conditions caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and no change or small increases in cardiac output. Under elevated tone conditions during infusion of U-46619, intravenous injections of BAY 60–2770 caused larger decreases in pulmonary arterial pressure, smaller decreases in systemic arterial pressure, and increases in cardiac output. Pulmonary vasodilator responses to BAY 60–2770 were enhanced by l-NAME or by ODQ in a dose that attenuated responses to the NO donor sodium nitroprusside. ODQ had no significant effect on baseline pressures and attenuated pulmonary and systemic vasodilator responses to the sGC stimulator BAY 41–8543 2-{1-[2-(fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}-5(4-morpholinyl)-4,6-pyrimidinediamine. BAY 60–2770 and sodium nitroprusside decreased pulmonary and systemic arterial pressures in monocrotaline-treated rats in a nonselective manner. The present data show that BAY 60–2770 has vasodilator activity in the pulmonary and systemic vascular beds that is enhanced by ODQ and NOS inhibition, suggesting that the heme-oxidized form of sGC can be

  3. Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase activator, BAY 60-2770, are not dependent on endogenous nitric oxide or reduced heme.

    PubMed

    Pankey, Edward A; Bhartiya, Manish; Badejo, Adeleke M; Haider, Umair; Stasch, Johannes-Peter; Murthy, Subramanyam N; Nossaman, Bobby D; Kadowitz, Philip J

    2011-03-01

    4-({(4-Carboxybutyl)[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}methyl)benzoic acid (BAY 60-2770) is a nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC) that increases the catalytic activity of the heme-oxidized or heme-free form of the enzyme. In this study, responses to intravenous injections of the sGC activator BAY 60-2770 were investigated under baseline and elevated tone conditions induced by the thromboxane mimic U-46619 when NO synthesis was inhibited by N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME), when sGC activity was inhibited by 1H-[1,2,4]-oxadizaolo[4,3]quinoxaline-1-one (ODQ), an agent that oxidizes sGC, and in animals with monocrotaline-induced pulmonary hypertension. The intravenous injections of BAY 60-2770 under baseline conditions caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and no change or small increases in cardiac output. Under elevated tone conditions during infusion of U-46619, intravenous injections of BAY 60-2770 caused larger decreases in pulmonary arterial pressure, smaller decreases in systemic arterial pressure, and increases in cardiac output. Pulmonary vasodilator responses to BAY 60-2770 were enhanced by L-NAME or by ODQ in a dose that attenuated responses to the NO donor sodium nitroprusside. ODQ had no significant effect on baseline pressures and attenuated pulmonary and systemic vasodilator responses to the sGC stimulator BAY 41-8543 2-{1-[2-(fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}-5(4-morpholinyl)-4,6-pyrimidinediamine. BAY 60-2770 and sodium nitroprusside decreased pulmonary and systemic arterial pressures in monocrotaline-treated rats in a nonselective manner. The present data show that BAY 60-2770 has vasodilator activity in the pulmonary and systemic vascular beds that is enhanced by ODQ and NOS inhibition, suggesting that the heme-oxidized form of sGC can be activated in vivo in an

  4. Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism

    PubMed Central

    Yang, Ying; Nie, Wei; Yuan, Jianmin; Zhang, Bingkun; Wang, Zhong

    2010-01-01

    Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser1179 which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models. PMID:20926919

  5. 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

  6. Evaluation of antigen-specific immunoglobulin g responses in pulmonary tuberculosis patients and contacts.

    PubMed

    Hur, Yun-Gyoung; Kim, Ahreum; Kang, Young Ae; Kim, An Sik; Kim, Dae Yeon; Kim, Yeun; Kim, Youngmi; Lee, Hyeyoung; Cho, Sang-Nae

    2015-03-01

    This study aimed to evaluate the serodiagnostic potential of immunoglobulin G (IgG) responses to Mycobacterium tuberculosis antigens in pulmonary tuberculosis (TB) patients, recent TB contacts with latent TB infection (LTBI), and healthy subjects. Infections were assessed using tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, drug susceptibility testing, and molecular genotyping of clinical isolates. Serum IgG responses to selective M. tuberculosis antigens, including the 38-kDa and 16-kDa antigens, lipoarabinomannan (LAM), and recombinant early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10), were determined. We found that the serum IgG responses to all antigens might differentiate between active TB and LTBI, with LAM having the highest diagnostic value (area under the curve [AUC] of 0.7756, P < 0.001). Recurrent TB cases showed significantly higher IgG responses to 38 kDa, CFP-10 (P < 0.01), and LAM (P < 0.05) than new cases, and male patients had higher levels of antigen-specific IgG than females (P < 0.05). Conversely, drug resistance and patient body mass index did not affect IgG responses (P > 0.05). LAM-specific IgG responses differentiated between acid-fast bacillus (AFB) smear-positive and -negative patients (P < 0.01), whereas antigen-specific IgG responses did not vary with the M. tuberculosis genotype (P > 0.05). Significantly higher IgG responses to 38 kDa and 16 kDa were observed in AFB smear-negative patients than in controls. These results suggest that assessment of serum IgG responses to selective purified M. tuberculosis antigens may help improve the diagnosis of active TB, particularly for sputum smear-negative patients or recurrent cases, and these may also help to differentiate between active TB and LTBI. PMID:25588651

  7. 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. PMID:25996154

  8. IL-27 and TGFβ mediated expansion of Th1 and adaptive regulatory T cells expressing IL-10 correlates with bacterial burden and disease severity in pulmonary tuberculosis.

    PubMed

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

    2015-09-01

    CD4(+) T cell expression of IL-10 is an important mechanism controlling immunity to tuberculosis (TB). To identify the CD4(+) T cell subsets producing IL-10 in human TB, we enumerated the frequencies of IL-10 expressing CD4(+) T cell subsets following TB-antigen stimulation of cells from individuals with pulmonary (PTB) and latent TB (LTB). We first demonstrate that TB antigens induce an expansion of IL-10 expressing Th1 (IL-10(+), IFNγ(+), T-bet(+)), Th2 (IL-10(+), IL-4(+), GATA-3(+)), Th9 (IL-10(+), IL-9(+), IL-4(-)), Th17 (IL-10(+), IL-17(+), IFNγ(-)), and natural and adaptive regulatory T cells [nTregs; IL-10(+), CD4(+), CD25(+), Foxp3(+) and aTregs; IL-10 single(+), CD4(+), CD25(-), Foxp3(-)] in PTB and LTB individuals, with frequencies being significantly higher in the former. However, only Th1 cells and adaptive Tregs expressing IL-10 exhibit a positive relationship with bacterial burdens and extent of disease in PTB. Finally, we show that IL-27 and TGFβ play an important role in the regulation of IL-10(+) Th cell subsets. Thus, active PTB is characterized by an IL-27 and TGFβ mediated expansion of IL-10 expressing CD4(+) T cell subsets, with IL-10(+) Th1 and IL-10(+) aTreg cells playing a potentially pivotal role in the pathogenesis of active disease. PMID:26417443

  9. 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

  10. 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

  11. Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam

    PubMed Central

    Nhung, N. V.; Hoa, N. B.; Thuy, H. T.; Takarinda, K. C.; Tayler-Smith, K.; Harries, A. D.

    2016-01-01

    Setting: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. Objectives: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010–2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010–2012. Design: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. Results: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Conclusion: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection—currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation. PMID:27051608

  12. Monocrotaline pyrrole-induced changes in angiotensin-converting enzyme activity of cultured pulmonary artery endothelial cells.

    PubMed Central

    Hoorn, C. M.; Roth, R. A.

    1993-01-01

    1. Changes in the structural and functional integrity of endothelium have been recognized as relatively early features of delayed and progressive pulmonary vascular injury caused by the pyrrolizidine alkaloid, monocrotaline (MCT). Although a number of investigators have evaluated angiotensin-converting enzyme (ACE) activity in the lungs of rats treated with MCT, the exact nature of changes in activity of this enzyme and the role they may play in MCT pneumotoxicity remain controversial. 2. We examined the direct effects of monocrotaline pyrrole (MCTP), a toxic metabolite of MCT, on cultured endothelial cell ACE activity. Post-confluent monolayers of porcine or bovine pulmonary artery endothelial cells (PECs or BECs, respectively) were treated with a single administration of MCTP at time 0; then they were examined for their ability to degrade the synthetic peptide, [3H]-benzoyl-Phe-Ala-Pro. 3. In PECs, which are relatively insensitive to the direct cytolytic effects of MCTP, monolayer ACE activity was unchanged initially but gradually decreased within 4 days after treatment with a high concentration of MCTP (150 microM). This decrease was transient, and PEC monolayer ACE activity returned to the control value by 10 days post treatment. 4. BEC monolayer ACE activity was also unchanged initially but rapidly declined within 4 days after MCTP treatment and remained depressed throughout the post treatment period. BECs were quite sensitive to the cytolytic effects of MCTP and the decline in ACE activity occurred coincident with the decrease in monolayer cellularity and appearance of marked cytotoxicity. 5. We conclude that high concentrations of MCTP decrease endothelial ACE activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8242234

  13. The Amiloride Derivative Phenamil Attenuates Pulmonary Vascular Remodeling by Activating NFAT and the Bone Morphogenetic Protein Signaling Pathway ▿

    PubMed Central

    Chan, Mun Chun; Weisman, Alexandra S.; Kang, Hara; Nguyen, Peter H.; Hickman, Tyler; Mecker, Samantha V.; Hill, Nicholas S.; Lagna, Giorgio; Hata, Akiko

    2011-01-01

    Pulmonary artery hypertension (PAH) is characterized by elevated pulmonary artery resistance and increased medial thickness due to deregulation of vascular remodeling. Inactivating mutations of the BMPRII gene, which encodes a receptor for bone morphogenetic proteins (BMPs), are identified in ∼60% of familial PAH (FPAH) and ∼30% of idiopathic PAH (IPAH) patients. It has been hypothesized that constitutive reduction in BMP signal by BMPRII mutations may cause abnormal vascular remodeling by promoting dedifferentiation of vascular smooth muscle cells (vSMCs). Here, we demonstrate that infusion of the amiloride analog phenamil during chronic-hypoxia treatment in rat attenuates development of PAH and vascular remodeling. Phenamil induces Tribbles homolog 3 (Trb3), a positive modulator of the BMP pathway that acts by stabilizing the Smad family signal transducers. Through induction of Trb3, phenamil promotes the differentiated, contractile vSMC phenotype characterized by elevated expression of contractile genes and reduced cell growth and migration. Phenamil activates the Trb3 gene transcription via activation of the calcium-calcineurin-nuclear factor of activated T cell (NFAT) pathway. These results indicate that constitutive elevation of Trb3 by phenamil is a potential therapy for IPAH and FPAH. PMID:21135135

  14. 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

  15. First-Line Treatment for Tuberculosis (TB), Drug Resistant TB -- A Visual Tour

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Drugs First-Line Treatment of TB for Drug- ... ago. See how these drugs work . Multidrug-Resistant Tuberculosis (MDR TB) and Second-Line Treatments MDR TB ...

  16. Neurohormonal activation and pharmacological inhibition in pulmonary arterial hypertension and related right ventricular failure.

    PubMed

    Ameri, Pietro; Bertero, Edoardo; Meliota, Giovanni; Cheli, Martino; Canepa, Marco; Brunelli, Claudio; Balbi, Manrico

    2016-09-01

    During the last decade, hyperactivity of the sympathetic nervous and renin-angiotensin-aldosterone systems (SNS and RAAS, respectively) has repeatedly been related to the pathophysiology of pulmonary arterial hypertension (PAH) and PAH-related right ventricular failure (PAH-RVF), raising the question of whether neurohormonal inhibition may be indicated for these conditions. Experimental data indicate that the RAAS may be involved in pulmonary vascular remodeling, which is in fact halted by RAAS antagonism. Favorable actions of β-blockers on the pulmonary vasculature have also been described, even if information about β-adrenergic receptors in PAH is lacking. Furthermore, the available evidence suggests that stimulation of the pressure-overloaded RV by the SNS and RAAS is initially compensatory, but becomes maladaptive over time. Consistently, RV reverse remodeling has been shown in PAH animal models treated with either β-blockers or RAAS inhibitors, although important differences with human PAH may limit the translational value of these findings. Only few observational studies of neurohormonal antagonism in PAH and PAH-RVF have been published. Nonetheless, β-blockers on top of specific therapy appear to be safe and possibly also effective. The combination of mineralocorticoid receptor and endothelin-A receptor antagonists may result in an additive effect because of a positive pharmacodynamic interaction. While neurohormonal inhibitors cannot be recommended at present for treatment of PAH and PAH-RVF, they are worth being further investigated. PMID:27206576

  17. Influence of annealing atmosphere and temperature on photoluminescence of Tb 3+ or Eu 3+-activated zinc silicate thin film phosphors via sol-gel method

    NASA Astrophysics Data System (ADS)

    Zhang, Q. Y.; Pita, K.; Ye, W.; Que, W. X.

    2002-01-01

    Thin films of Zn 2SiO 4:Tb 3+ or Eu 3+ were deposited on silicon wafers by a sol-gel method. The films exhibited prominent green or red photoluminescence, due to the sharp and strong intra-4f n-shell electronic transitions. The thermogravimetric analysis curve shows a remarkable weight loss in the temperature range 50-400 ° C, and a slow loss at higher temperature. The increases in fluorescence intensity and decay lifetimes of rare-earth ions sensitive to microstructure and chemical components are attributed to OH removal, nano-crystallite formation and the increased surface roughness by treatment of temperature. Strongly enhanced photoluminescence was observed in samples annealed at 950 °C in a nitrogen atmosphere.

  18. Changes of Tb Emission by Non-radiative Energy Transfer from Dy in Gd2O2S:Tb Phosphor

    NASA Astrophysics Data System (ADS)

    Saraee, Kh. Rezaee Ebrahim; Zadeh, M. Darvish; Mostajaboddavati, M.; Kharieky, A. Aghay

    2016-06-01

    In this study, the Gd2O2S:Tb1.5Dy x=0.3,0.6,0.9 nanophosphor were synthesized by the homogenous precipitation method followed with a sulfur reaction. The fluorescence of Gd2O2S:Tb1.5,Dy nanophosphors, and the energy transfer between dysprosium (Dy) and Tb have been studied. Although, the two weak emissions of Dy were observed, the terbium (Tb) emission was increased due to energy transfer from Dy ions to Tb ions. The results illustrated that the co-activator of Dy had a significant influence on the spectral properties of the Gd2O2S:Tb1.5 nanophosphor with an optimal amount of Dy (0.3 mol%). Moreover, Gd2O2S:Tb1.5 and Gd2O2S:Tb1.5,Dy nanophosphors screens were prepared with 10 mg/cm2 coating thickness. The scintillation properties of these screens have been investigated. We found a Gd2O2S:Tb1.5,Dy0.3 scintillator can be employed in x-ray imaging applications.

  19. 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.

  20. An Innovative Method to Enhance the Modified DOTS for TB Patients

    PubMed Central

    Yekrang Sis, Hassan; Azabdaftari, Fariba; Mahdavi Poor, Behroz; Asgharzadeh, Mohammad; Jannati, Ali; Asghari Jafarabadi, Mohammad

    2015-01-01

    Background: Nowadays establishing communication and educating patients to enhance their knowledge regarding disease and treatment process at home is one of the most important principles in providing patient care. Materials and Methods: A semi-experimental study was done on 57 patients with active pulmonary tuberculosis in two care groups namely professional – family mix directly observed treatment short- course (PFM-DOTS) and family based-DOTS (FB-DOTS). The patients were referred to the tuberculosis and lung diseases research center for diagnosis and treatment of pulmonary tuberculosis. Both the patient and a family supervisor were evaluated regarding their level of knowledge of the disease and the treatment regimen. Results: A significant difference between the degree of knowledge of groups of patients and the groups of family relatives before and after the intervention was indicated, with a higher increase in PFM-DOTS group than in F-B-DOTS group (P< 0.001). In PFM- DOTS group 100% of the patients, and in the FB-DOTS group 86.8% of the patients followed the recommended drug regimen (P<0.001). Conclusion: According to the treatment recommendations by the World Health Organization (WHO) for appropriate implementation of DOTS project combating TB, it seems the PFM-DOTS implementation is a more suitable method with greater effects on correct care and treatment of tuberculosis patients. PMID:26858763

  1. Fast and intense green emission of Tb3+ in borosilicate glass modified by Cu+

    PubMed Central

    Xia, Fanshu; Liu, Siyuan; Wang, Yang; Mao, Jiayi; Li, Xinxi; Wang, Yiqun; Chen, Guorong

    2015-01-01

    We present photoluminescence properties of Tb3+ doped borosilicate glasses modified by Cu+. Around 5-time enhanced emission at 541 nm due to the superposed emission of Tb3+ and Cu+ is observed under the deep UV excitation. Excitation spectra demonstrate a greatly increased absorption of Tb3+ ions in the deep UV region towards the Cu+ excitation band, while the shortened Cu+ emission lifetime of glasses in association with presence of Tb3+ ions implies an energy transfer process from Cu+ to Tb3+ ions. Meanwhile, the Tb3+ emission lifetime is significantly shortened from the conventional millisecond level (~4 ms) to the microsecond regime up to around 90 μs. This most likely starts with the role of Cu+ as a co-activator by initiating the d-f orbital hybridization process via an interaction with Tb3+, thus relaxing the spin forbidden transition of Tb3+ ions to the partially allowed one. Moreover, combination of emissions from Cu+ and Tb3+ ions generates a composite green emission with adjustable CIE (Commission Internationale de L’Eclairage) chromaticity coordinates achievable by co-doping Cu+/Tb3+ in the different ratio and/or altering the excitation wavelength from deep UV to near UV region. PMID:26487264

  2. Fast and intense green emission of Tb3+ in borosilicate glass modified by Cu+

    NASA Astrophysics Data System (ADS)

    Xia, Fanshu; Liu, Siyuan; Wang, Yang; Mao, Jiayi; Li, Xinxi; Wang, Yiqun; Chen, Guorong

    2015-10-01

    We present photoluminescence properties of Tb3+ doped borosilicate glasses modified by Cu+. Around 5-time enhanced emission at 541 nm due to the superposed emission of Tb3+ and Cu+ is observed under the deep UV excitation. Excitation spectra demonstrate a greatly increased absorption of Tb3+ ions in the deep UV region towards the Cu+ excitation band, while the shortened Cu+ emission lifetime of glasses in association with presence of Tb3+ ions implies an energy transfer process from Cu+ to Tb3+ ions. Meanwhile, the Tb3+ emission lifetime is significantly shortened from the conventional millisecond level (~4 ms) to the microsecond regime up to around 90 μs. This most likely starts with the role of Cu+ as a co-activator by initiating the d-f orbital hybridization process via an interaction with Tb3+, thus relaxing the spin forbidden transition of Tb3+ ions to the partially allowed one. Moreover, combination of emissions from Cu+ and Tb3+ ions generates a composite green emission with adjustable CIE (Commission Internationale de L’Eclairage) chromaticity coordinates achievable by co-doping Cu+/Tb3+ in the different ratio and/or altering the excitation wavelength from deep UV to near UV region.

  3. Fast and intense green emission of Tb(3+) in borosilicate glass modified by Cu(.).

    PubMed

    Xia, Fanshu; Liu, Siyuan; Wang, Yang; Mao, Jiayi; Li, Xinxi; Wang, Yiqun; Chen, Guorong

    2015-01-01

    We present photoluminescence properties of Tb(3+) doped borosilicate glasses modified by Cu(+). Around 5-time enhanced emission at 541 nm due to the superposed emission of Tb(3+) and Cu(+) is observed under the deep UV excitation. Excitation spectra demonstrate a greatly increased absorption of Tb(3+) ions in the deep UV region towards the Cu(+) excitation band, while the shortened Cu(+) emission lifetime of glasses in association with presence of Tb(3+) ions implies an energy transfer process from Cu(+) to Tb(3+) ions. Meanwhile, the Tb(3+) emission lifetime is significantly shortened from the conventional millisecond level (~4 ms) to the microsecond regime up to around 90 μs. This most likely starts with the role of Cu(+) as a co-activator by initiating the d-f orbital hybridization process via an interaction with Tb(3+), thus relaxing the spin forbidden transition of Tb(3+) ions to the partially allowed one. Moreover, combination of emissions from Cu(+) and Tb(3+) ions generates a composite green emission with adjustable CIE (Commission Internationale de L'Eclairage) chromaticity coordinates achievable by co-doping Cu(+)/Tb(3+) in the different ratio and/or altering the excitation wavelength from deep UV to near UV region. PMID:26487264

  4. Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis

    PubMed Central

    Chung, Kuei-Pin; Chen, Jung-Yueh; Lee, Chih-Hsin; Wu, Huey-Dong; Wang, Jann-Yuan; Lee, Li-Na; Yu, Chong-Jen; Yang, Pan-Chyr

    2011-01-01

    OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment. PMID:21655745

  5. TB deaths reach historic levels. International (global).

    PubMed

    More tuberculosis (TB)-related deaths occurred in 1995 than in any other year in history (almost 3 million, vs. 2.1 million for the TB epidemic around 1990). In the next 50 years, as many as 500 million people may develop TB if current rates continue. More and more of these people will develop multidrug resistant TB. TB affects all social groups. It is the leading fatal infection in youth and adults. HIV positive people are more likely to die from TB than any other condition. More women die from TB than all causes of maternal mortality combined. Almost 50% of the world's refugees may have TB. All people are at risk of TB since TB bacteria, which enter the air via coughing or sneezing, can be suspended in the air for hours. Increased air travel and migration have brought TB back to industrialized countries. Multi-drug resistant TB has emerged in New York City, London, Milan, Paris, Atlanta, Chicago, and cities in developing countries. Governments of industrialized and developing countries have been slow to understand the effects of multi-drug resistant TB for public health. During the 1970s and 1980s, TB was greatly neglected resulting in the current multi-drug resistant TB epidemic. Policy makers have not applied the tools discovered by scientists to help eliminate TB. The World Health Organization recommends directly observed treatment, short-course (DOTS) to fight TB. DOTS can increase the number of cured TB patients two-fold. It can cure almost 95% of TB patients with medicines costing less than $11 in some areas of the world. Yet DOTS is being used to cure only 10% of all TB patients in the world. If it were used in Bangladesh, Brazil, China, Ethiopia, India, Indonesia, Mexico, Nigeria, Pakistan, Russian Federation, South Africa, and Zaire, about 75% of all TB cases would be cured. In DOTS, health workers, not the TB patient, are responsible for curing the TB patient. Poor patient compliance is responsible for the current TB epidemic because TB patients remain

  6. 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. PMID:25763996

  7. 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. PMID:26542392

  8. Pulmonary rehabilitation in adults.

    PubMed

    2016-06-01

    Pulmonary rehabilitation can help people with long-term lung conditions whose symptoms, such as breathlessness and being easily tired out by daily activities, seriously impact their lives. PMID:27408642

  9. 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. PMID:20855539

  10. 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

  11. Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1

    PubMed Central

    2010-01-01

    Background Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. Methods Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. Results We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. Conclusions Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals. PMID:21176193

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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. PMID:25790942

  16. Plasma Adenosine Deaminase Enzyme Reduces with Treatment of Pulmonary Tuberculosis in Nigerian Patients: Indication for Diagnosis and Treatment Monitoring.

    PubMed

    Ige, O; Edem, V F; Arinola, O G

    2016-01-01

    Tuberculosis(TB)-specific host biomarkers for diagnosis and monitoring of treatment response have been identified as priorities for TB research. Macrophage and T cell lymphocytes play vital roles in Mycobacterium tuberculosis immune response and their associated biomarkers could form good candidates for diagnosis and treatment monitoring. The enzyme adenosine deaminase (ADA) is produced mainly by monocytes and macrophages and increase in biological fluids in the course of infection with microorganisms infecting macrophages. This study comprised sixty-eight (68) participants; twenty-four (24) multi-drug-resistant TB(MDR-TB) patients, twenty-four (24) drug-sensitive TB patients(DS-TB) and twenty (20) non-TB apparently healthy individuals. Five (5) milliliters of blood was drawn before commencement of chemotherapy and 6 anti-TB therapy. In DSTB and MDR-TB patients before commencement of chemotherapy and 6 months of anti-TB treatment, the mean plasma levels of ADA were significantly increased compared with control. At 6 months of anti-TB chemotherapy of DSTB or MDR TB patients, ADA level was significantly decreased compared with before chemotherapy. Plasma ADA in DSTB patients before and 6 months of chemotherapy were not significantly different compared MDR TB patients. Plasma ADA level is a promising biomarker for the screening and treatment monitoring of pulmonary tuberculosis but not to differentiate MDR TB from DSTB patients. PMID:27574764

  17. Polymorphisms of SP110 Are Associated with both Pulmonary and Extra-Pulmonary Tuberculosis among the Vietnamese

    PubMed Central

    Fox, Gregory J.; Sy, Dinh Ngoc; Nhung, Nguyen Viet; Yu, Bing; Ellis, Magda K.; Van Hung, Nguyen; Cuong, Nguyen Kim; Thi Lien, Luu; Marks, Guy B.; Saunders, Bernadette M.; Britton, Warwick J.

    2014-01-01

    Background Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection. PMID:25006821

  18. HIV-TB coinfection: Clinico-epidemiological determinants at an antiretroviral therapy center in Southern India

    PubMed Central

    Kamath, Ramachandra; Sharma, Vikram; Pattanshetty, Sanjay; Hegde, Mohandas B.; Chandrasekaran, Varalakshmi

    2013-01-01

    Background: HIV–TB (tuberculosis) coinfection has emerged as a major public health threat. Given the multifactorial enabling environment in a resource-constrained setting like India, the consequences are of epidemic proportions. Aims: This study was aimed at identifying the clinical and epidemiological determinants underlying HIV–TB coinfection. Settings and Design: A retrospective review of patient records was done from the antiretroviral therapy center (ART) center at a district hospital in southern India between May and August 2012. Materials and Methods: Secondary data of 684 patients on ART as well as pre-ART were collected between July 2008 and June 2012 and were analyzed. Statistical Analysis: Descriptive analysis, χ2, and Wilcoxon signed rank tests were used with SPSS version 15.0 to draw significant statistical inferences. Results: HIV–TB coinfection was diagnosed in 18.9% with higher prevalence among males (75.3%), in the sexually active age group 31-45 years (61.3%), with less than primary education (44.15%), who were married (56.1%), laborers (42.4%), from rural backgrounds (88.2%), and having low income-earning capacity (94.4%). Transmission was predominantly through the heterosexual route. The key entry point was the integrated counseling and testing center (ICTC) (47.4%). Pulmonary tuberculosis (58.8%) was predominantly found followed by extrapulmonary tuberculosis (38.2%) and both in 3.1%. A favorable outcome was observed in 69.3% of coinfected patients with 89.2% on ART and 97.2% currently on DOTS therapy. The Wilcoxon signed-rank test found significant association between rises in CD4 counts after the 6th-month follow up (P < 0.05). Coinfected patients had a case fatality rate of 25%. Conclusions: The prevalence of HIV–TB coinfection recorded in this sample was 18.86%. ICTC implemented by NACO emerged as an effective entry point, while Revised National Tuberculosis Control Program referred 1.6% (n = 11) of the patients to the ART center

  19. Pulmonary Embolism.

    PubMed

    Rali, Parth; Gandhi, Viral; Malik, Khalid

    2016-01-01

    Pulmonary embolism covers a wide spectrum of presentation from an asymptomatic individual to a life-threatening medical emergency. It is of paramount importance to appropriately risk stratify patients with pulmonary embolism, particularly with those who present without hypotension. Right ventricular dysfunction can evolve after a patient has received a diagnosis of pulmonary embolism, necessitating aggressive measures rather than simple anticoagulation. In this review, we discuss definition, risk stratification, pathogenesis, diagnostic approach, and management, with particular focus on massive pulmonary embolism. PMID:26919674

  20. 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

  1. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis

    PubMed Central

    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

    2016-01-01

    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

  2. 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

  3. 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.

  4. Early Macrophage Recruitment and Alternative Activation Are Critical for the Later Development of Hypoxia-induced Pulmonary Hypertension

    PubMed Central

    Vergadi, Eleni; Chang, Mun Seog; Lee, Changjin; Liang, Olin; Liu, Xianlan; Fernandez-Gonzalez, Angeles; Mitsialis, S. Alex; Kourembanas, Stella

    2011-01-01

    Background Lung inflammation precedes the development of hypoxia-induced pulmonary hypertension (HPH); however its role in the pathogenesis of HPH is poorly understood. We sought to characterize the hypoxic inflammatory response and elucidate its role in the development of HPH. We also aimed to investigate the mechanisms by which heme oxygenase-1 (HO-1), an anti-inflammatory enzyme, is protective in HPH. Methods and Results We generated bitransgenic mice that overexpress human HO-1 under doxycycline (dox) control in an inducible, lung-specific manner. Hypoxic exposure of mice in the absence of dox resulted in early transient accumulation of monocytes/macrophages in the bronchoalveolar lavage. Alveolar macrophages acquired an alternatively activated phenotype (M2) in response to hypoxia, characterized by the expression of Found in Inflammatory Zone-1, Arginase-1 and Chitinase-3-like-3. A brief, two-day pulse of dox delayed but did not prevent the peak of hypoxic inflammation, and could not protect from HPH. In contrast, a seven-day dox treatment sustained high HO-1 levels during the entire period of hypoxic inflammation, inhibited macrophage accumulation and activation, induced macrophage IL-10 expression, and prevented the development of HPH. Supernatants from hypoxic M2 macrophages promoted proliferation of pulmonary artery smooth muscle cells while treatment with carbon monoxide, a HO-1 enzymatic product, abrogated this effect. Conclusions Early recruitment and alternative activation of macrophages in hypoxic lungs is critical for the later development of HPH. HO-1 may confer protection from HPH by effectively modifing macrophage activation state in hypoxia. PMID:21518986

  5. 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. PMID:26369587

  6. Protein Kinase D Is Increased and Activated in Lung Epithelial Cells and Macrophages in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Gan, Huachen; McKenzie, Raymond; Hao, Qin; Idell, Steven; Tang, Hua

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and usually fatal lung disease of unknown etiology for which no effective treatments currently exist. Hence, there is a profound need for the identification of novel drugable targets to develop more specific and efficacious therapeutic intervention in IPF. In this study, we performed immunohistochemical analyses to assess the cell type-specific expression and activation of protein kinase D (PKD) family kinases in normal and IPF lung tissue sections. We also analyzed PKD activation and function in human lung epithelial cells. We found that PKD family kinases (PKD1, PKD2 and PKD3) were increased and activated in the hyperplastic and regenerative alveolar epithelial cells lining remodeled fibrotic alveolar septa and/or fibroblast foci in IPF lungs compared with normal controls. We also found that PKD family kinases were increased and activated in alveolar macrophages, bronchiolar epithelium, and honeycomb cysts in IPF lungs. Interestingly, PKD1 was highly expressed and activated in the cilia of IPF bronchiolar epithelial cells, while PKD2 and PKD3 were expressed in the cell cytoplasm and nuclei. In contrast, PKD family kinases were not apparently increased and activated in IPF fibroblasts or myofibroblasts. We lastly found that PKD was predominantly activated by poly-L-arginine, lysophosphatidic acid and thrombin in human lung epithelial cells and that PKD promoted epithelial barrier dysfunction. These findings suggest that PKD may participate in the pathogenesis of IPF and may be a novel target for therapeutic intervention in this disease. PMID:25000413

  7. TB-HIV co-infection: a catastrophic comradeship.

    PubMed

    Narendran, G; Swaminathan, S

    2016-04-01

    The symbiotic association of tuberculosis (TB) and HIV poses a challenge to human survival. HIV complicates every aspect of TB including presentation, diagnosis and treatment. HIV-TB patients encounter unique problems like drug-drug interactions, cumulative toxicity, immune reconstitution inflammatory syndrome (IRIS), lower plasma drug levels and emergence of drug resistance during treatment despite adherence. TB may also be overdiagnosed in HIV due to a number of diseases that closely resemble TB. Notable among them are non-tuberculous mycobacteria, Pneumocystis Jirovecii and Nocardia. Even though diagnostic procedures have improved over the years, patients in developing countries usually seek health care at later stage of the disease. Research data ascertains the duration of therapy for TB to be 6 months with rifampicin and isoniazid, reinforced with ethambutol and pyrazinamide in the first 2 months. The schedule of therapy is still debatable with daily regimens being preferred in the context of HIV. Many reasons exist for persistence of Mycobacterium Tuberculosis (M.TB) in sputum, or delayed-clearance of TB from sputum smears in HIV, apart from emergence of drug resistance and non-compliance. Acquired rifampicin resistance (ARR) is a unique phenomenon complicating HIV-associated TB when an intermittent regimen of antituberculosis therapy (ATT) is used without timely initiation of highly active antiretroviral therapy (HAART), especially in patients harbouring isoniazid-resistant strains Immune restoration is often incomplete ('swiss cheese' pattern) even with effective HAART if not started early. Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening of the patient's condition often with radiological deterioration, due to an enhanced immune response with HAART. IRIS occurs despite an effective virological suppression and a favourable response to ATT. The incidence of IRIS in HIV has reached up to 54%, requiring utilization of experts

  8. 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

  9. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  10. Extensively Drug-Resistant Tuberculosis (XDR TB)

    MedlinePlus

    ... other federal agencies and international partners to raise awareness and enhance strategies for TB prevention worldwide by: Strengthening TB services for people living with HIV/AIDS; Guiding preparedness and outbreak investigation responses; Improving ...

  11. TB in Children in the United States

    MedlinePlus

    ... Statistics Related Links TB in Children in the United States TB disease in children under 15 years ... BCG vaccine is not generally used in the United States, because of the low risk of infection ...

  12. [Unsaturated fatty acid of Actinidia chinesis Planch seed oil enhances the antioxidative stress ability of rats with pulmonary fibrosis through activating Keap 1/Nrf 2 signaling pathway].

    PubMed

    Liu, Lijing; Qian, Hong; Yin, Huiming; He, Jianbin; Zhang, Ping; Wang, Zaiyan

    2016-04-01

    indicators were significantly improved in 120 and 180 mg/kg USFA-ACP seed oil treatment group and prednisone group. However, there was no significant difference between 120 and 180 mg/kg USFA-ACP seed oil treatment groups and prednisone group. Conclusion USFA-ACP seed oil can inhibit pulmonary fibrosis in rats, and the mechanism may be associated with the activation of the Keap1/Nrf 2 signaling pathway to increase the production of antioxidases in the pulmonary tissues. PMID:27053614

  13. miR-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension

    PubMed Central

    Stevens, Hannah; Lu, Ruifang; Caudrillier, Axelle; McBride, Martin; McClure, John D; Grant, Jenny; Thomas, Matthew; Frid, Maria; Stenmark, Kurt; White, Kevin; Seto, Anita G.; Morrell, Nicholas W.; Bradshaw, Angela C; MacLean, Margaret R.; Baker, Andrew H.

    2015-01-01

    Rationale The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143−/− and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions miR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology. PMID:26311719

  14. Aptamer-based Proteomic Signature of Intensive Phase Treatment Response in Pulmonary Tuberculosis

    PubMed Central

    Nahid, Payam; Bliven-Sizemore, Erin; Jarlsberg, Leah G.; Mary, A; Groote, De; Johnson, John L.; Muzanyi, Grace; Engle, Melissa; Weiner, Marc; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2014-01-01

    Background New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. Methods In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. Results We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC=0.96, sensitivity=0.95 and specificity=0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). Conclusions Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study. PMID:24629635

  15. Suppressed Type 1, Type 2, and Type 17 Cytokine Responses in Active Tuberculosis in Children ▿ †

    PubMed Central

    Kumar, N. Pavan; Anuradha, R.; Suresh, R.; Ganesh, R.; Shankar, Janani; Kumaraswami, V.; Nutman, Thomas B.; Babu, Subash

    2011-01-01

    Type 1 cytokine responses are known to play an important role in immunity to tuberculosis (TB) in children, although little is known about other factors that might be important. In addition, children are more prone to developing extrapulmonary manifestations of TB than adults. To identify the immune responses important both in control of infection and in extrapulmonary dissemination, we examined mycobacterium-specific cytokine responses of children with pulmonary TB (PTB) and extrapulmonary TB (ETB) and compared them with those of healthy control children (HC). No significant differences were found in the cytokine responses either with no stimulation or following mycobacterial-antigen (Ag) stimulation between children with PTB and ETB. On the other hand, children with active TB compared with HC showed markedly diminished production of type 1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), 2 (interleukin 4 [IL-4] and IL-13), and 17 (IL-17A, IL-21, and IL-23)-associated cytokines with no stimulation and in response to mycobacterial antigens. This was not associated with significantly altered production of IL-10 or transforming growth factor β (TGF-β). Among children with ETB, those with neurologic involvement exhibited more significantly diminished Ag-driven IFN-γ and IL-17 production. Pediatric TB is characterized by diminished type 1, 2, and 17 cytokine responses, with the most profound diminution favoring development of neurologic TB, suggesting a crucial role for these cytokines in protection against pediatric tuberculosis. PMID:21955625

  16. Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy

    PubMed Central

    Ravimohan, Shruthi; Tamuhla, Neo; Kung, Shiang-Ju; Nfanyana, Kebatshabile; Steenhoff, Andrew P.; Gross, Robert; Weissman, Drew; Bisson, Gregory P.

    2015-01-01

    Background HIV-infected patients with pulmonary TB (pTB) can have worsening of respiratory symptoms as part of TB-immune reconstitution inflammatory syndrome (TB-IRIS) following antiretroviral therapy (ART) initiation. Thus, reconstitution of immune function on ART could drive incident lung damage in HIV/TB. Methods We hypothesized that increases in matrix metalloproteinases (MMPs), which can degrade lung matrix, on ART are associated with TB-IRIS among a cohort of advanced, ART naïve, HIV-infected adults with pTB. Furthermore, we related early changes in immune measures and MMPs on ART to lung function in an exploratory subset of patients post-TB cure. This study was nested within a prospective cohort study. Rank sum and chi-square tests, Spearman's correlation coefficient, and logistic regression were used for analyses. Results Increases in MMP-8 following ART initiation were independently associated with TB-IRIS (p = 0.04; adjusted odds ratio 1.5 [95% confidence interval: 1.0–2.1]; n = 32). Increases in CD4 counts and MMP-8 on ART were also associated with reduced forced expiratory volume in one-second post-TB treatment completion (r = − 0.7, p = 0.006 and r = − 0.6, p = 0.02, respectively; n = 14). Conclusions ART-induced MMP increases are associated with TB-IRIS and may affect lung function post-TB cure. End-organ damage due to TB-IRIS and mechanisms whereby immune restoration impairs lung function in pTB deserve further investigation. PMID:27014741

  17. 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

  18. 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

  19. Reliability and Validity of the Multimedia Activity Recall in Children and Adults (MARCA) in People with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Hunt, Toby; Williams, Marie T.; Olds, Tim S.

    2013-01-01

    Objective To determine the reliability and validity of the Multimedia Activity Recall for Children and Adults (MARCA) in people with chronic obstructive pulmonary disease (COPD). Design People with COPD and their carers completed the Multimedia Activity Recall for Children and Adults (MARCA) for four, 24-hour periods (including test-retest of 2 days) while wearing a triaxial accelerometer (Actigraph GT3X+®), a multi-sensor armband (Sensewear Pro3®) and a pedometer (New Lifestyles 1000®). Setting Self reported activity recalls (MARCA) and objective activity monitoring (Accelerometry) were recorded under free-living conditions. Participants 24 couples were included in the analysis (COPD; age 74.4±7.9 yrs, FEV1 54±13% Carer; age 69.6±10.9 yrs, FEV1 99±24%). Interventions Not applicable. Main Outcome Measure(s) Test-retest reliability was compared for MARCA activity domains and different energy expenditure zones. Validity was assessed between MARCA-derived physical activity level (in metabolic equivalent of task (MET) per minute), duration of moderate to vigorous physical activity (min) and related data from the objective measurement devices. Analysis included intra-class correlation coefficients (ICC), Bland-Altman analyses, paired t-tests (p) and Spearman's rank correlation coefficients (rs). Results Reliability between occasions of recall for all activity domains was uniformly high, with test-retest correlations consistently >0.9. Validity correlations were moderate to strong (rs = 0.43–0.80) across all comparisons. The MARCA yields comparable PAL estimates and slightly higher moderate to vigorous physical activity (MVPA) estimates. Conclusion In older adults with chronic illness, the MARCA is a valid and reliable tool for capturing not only the time and energy expenditure associated with physical and sedentary activities but also information on the types of activities. PMID:24312284

  20. 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.

  1. 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

  2. [Monoclonal human immunoglobulin (IgG lambda) with antiethinylestradiol activity, oral contraceptives, and arterial pulmonary thrombosis].

    PubMed

    Beaumont, J L; Lemort, N

    1975-06-23

    In a 36-year-old woman taking an oral contraceptive containing 50 mug of ethinyloestradiol each day, a pulmonary arterial thrombosis and a monoclonal gammapathia were associated. The monoclonal IgI lambda Mai... was prepared. When purified, this IgG lambda binds ethinyloestradiol with strong affinity (Ka= 2.7 times 10(7)M-1) and also 17-beta-oestradiol with a little less affinity (Ka = 0.4 times 10(7)M-1. For those ligands each IgG lambda Mai... molecule has two sites of same affinity and specificity so that a Scatchard plot of the experimental values gives a straight line. It is likely that the antibody sites of the IgG lambda Mai... are the binding sites. These facts support the hypothesis of an immunological mechanism of the thromboembolic disease which may be induced by oral contraceptives. PMID:808320

  3. 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.

  4. Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria

    PubMed Central

    Soares, A C; Pinho, V S; Souza, D G; Shimizu, T; Ishii, S; Nicoli, J R; Teixeira, M M

    2002-01-01

    The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-α and IL-8. Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice. At an inoculum of 3×106 bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-α increased rapidly and persisted for 48 h in the lungs. Pretreatment with UK-74,505 (30 mg kg−1 per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-α and the number of bacteria inside neutrophils were significantly diminished. In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm. Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice. PMID:12381675

  5. Obstructive Sleep Apnea Hypopnea Syndrome as a Reason for Active Management of Pulmonary Embolism

    PubMed Central

    Xie, Jiang; Wei, Yong-Xiang; Liu, Shuang; Zhang, Wei; Zhang, Xiang-Feng; Li, Jie

    2015-01-01

    Background: Obstructive sleep apnea hypopnea syndrome (OSAHS) constitutes an independent factor for high warfarin dose for patients with pulmonary embolism (PE). The aim of this study was to investigate whether the 6-month anticoagulation treatment by warfarin is enough for patients with PE complicated by OSAHS. Methods: We investigated 97 PE patients, 32 of them had OSAHS and 65 non-OSAHS. Warfarin was administered for 6-month if no abnormal circumstances occurred. All patients were followed up for 18 months. Adverse events (AE) included death, major bleeding, hospitalization due to heart failure or pulmonary hypertension, and recurrence or aggravation of PE (including deep vein thrombosis). Recurrence rate of PE after warfarin cessation was compared between the two groups. Results: OSAHS patients required a significantly higher dose of warfarin than their non-OSAHS counterparts (4.73 mg vs. 3.61 mg, P < 0.001). During warfarin treatment, no major bleeding and aggravation of PE occurred among OSAHS patients, and the rates of various AE were not significantly different between the OSAHS and non-OSAHS groups. PE recurrence was higher in OSAHS than non-OSAHS groups after withdrawal of warfarin (21.43% vs. 6.78%, P = 0.047). Compared with non-OSAHS patients, OSAHS group had lower international normalized ratio (INR) value but higher plasminogen on baseline and INR resumed to a relatively low level after warfarin discontinuation. Conclusions: OSAHS patients may present with hypercoagulation and relatively high-risk of recurrence of PE after cessation of 6-month warfarin treatment. PMID:26265606

  6. Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages.

    PubMed

    Xiang, Juan; Cheng, Si; Feng, Tianlong; Wu, Yan; Xie, Weina; Zhang, Mian; Xu, Xianghong; Zhang, Chaofeng

    2016-07-01

    Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages. PMID:27144994

  7. 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)

  8. Drug-resistant pulmonary tuberculosis in the Baja California-San Diego County border population.

    PubMed

    Peter, C R; Schultz, E; Moser, K; Cox, M; Freeman, R; Ramirez-Zetina, M; Lomeli, M R

    1998-10-01

    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

  9. Activation of Sterol-response Element-binding Proteins (SREBP) in Alveolar Type II Cells Enhances Lipogenesis Causing Pulmonary Lipotoxicity*

    PubMed Central

    Plantier, Laurent; Besnard, Valérie; Xu, Yan; Ikegami, Machiko; Wert, Susan E.; Hunt, Alan N.; Postle, Anthony D.; Whitsett, Jeffrey A.

    2012-01-01

    Pulmonary inflammation is associated with altered lipid synthesis and clearance related to diabetes, obesity, and various inherited metabolic disorders. In many tissues, lipogenesis is regulated at the transcriptional level by the activity of sterol-response element-binding proteins (SREBP). The role of SREBP activation in the regulation of lipid metabolism in the lung was assessed in mice in which both Insig1 and Insig2 genes, encoding proteins that bind and inhibit SREBPs in the endoplasmic reticulum, were deleted in alveolar type 2 cells. Although deletion of either Insig1 or Insig2 did not alter SREBP activity or lipid homeostasis, deletion of both genes (Insig1/2Δ/Δ mice) activated SREBP1, causing marked accumulation of lipids that consisted primarily of cholesterol esters and triglycerides in type 2 epithelial cells and alveolar macrophages. Neutral lipids accumulated in type 2 cells in association with the increase in mRNAs regulating fatty acid, cholesterol synthesis, and inflammation. Although bronchoalveolar lavage fluid phosphatidylcholine was modestly decreased, lung phospholipid content and lung function were maintained. Insig1/2Δ/Δ mice developed lung inflammation and airspace abnormalities associated with the accumulation of lipids in alveolar type 2 cells, alveolar macrophages, and within alveolar spaces. Deletion of Insig1/2 activated SREBP-enhancing lipogenesis in respiratory epithelial cells resulting in lipotoxicity-related lung inflammation and tissue remodeling. PMID:22267724

  10. Physical activity levels improve following discharge in people admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Tsai, Ling Ling Y; Alison, Jennifer A; McKenzie, David K; McKeough, Zoe J

    2016-02-01

    This study aimed to determine the physical activity level of people admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and whether physical activity changed immediately after discharge and 6 weeks post hospital admission. In this prospective observational study, people admitted to hospital with an AECOPD had physical activity levels monitored using the SenseWear(®) Armband (model MF-SW) for 3 days in hospital (T1), during the first week at home following discharge (T2), and at home during the sixth week after admission (T3). Fifty participants (mean age (SD) 71 (10) years) completed the study. There was a linear increase in average steps per day over the three time periods (T1, mean (SD) 1385 (1972) steps/day; T2, 2040 (2680); T3, 2328 (2745); analysis of variance (ANOVA) p = 0.001) and time spent in moderate activity (3.0-6.0 metabolic equivalents; minutes/day) (T1, mean (SD) 16 (27) minutes/day; T2, 32 (46) minutes/day; T3, 35 (58) minutes/day; ANOVA p = 0.008). For both outcomes, post hoc t-tests showed significant improvements from T1 to T2 and from T1 to T3, but not between T2 and T3. Physical activity was low in hospital and significantly improved in the week after discharge but showed no further significant improvement at 6 weeks following a hospitalized AECOPD. PMID:26374299

  11. Validating a Scoring System for the Diagnosis of Smear-Negative Pulmonary Tuberculosis in HIV-Infected Adults

    PubMed Central

    Coimbra, Isabella; Maruza, Magda; Albuquerque, Maria de Fátima Pessoa Militão; Batista, Joanna D’Arc Lyra; Braga, Maria Cynthia; Moura, Líbia Vilela; Miranda-Filho, Demócrito Barros; Montarroyos, Ulisses Ramos; Lacerda, Heloísa Ramos; Rodrigues, Laura Cunha; de Alencar Ximenes, Ricardo Arraes

    2014-01-01

    Background The challenge of diagnosing smear-negative pulmonary TB (tuberculosis) in people living with HIV justifies the use of instruments other than the smear test for diagnosing the disease. Considering the clinical-radiological similarities of TB amongst HIV-infected adults and children, the proposal of this study was to assess the accuracy of a scoring system used to diagnose smear-negative pulmonary TB in children and adolescents, in HIV-infected adults suspected of having smear-negative pulmonary TB. Methods A Phase III validation study aiming to assess the diagnostic accuracy of a scoring system for diagnosing smear-negative pulmonary TB in HIV-infected adults. The study assessed sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values of the scoring system. Three versions of the scoring system were tested. Results From a cohort of 2,382 (HIV-infected adults), 1276 were investigated and 128 were diagnosed with pulmonary TB. Variables associated with the diagnosis of TB were: coughing, weight loss, fever, malnutrition, chest X-ray, and positive tuberculin test. The best diagnostic performance occurred with the scoring system with new scores, with sensitivity = 81.2% (95%-CI 74.5% –88%), specificity = 78% (75.6% –80.4%), PPV = 29.2% (24.5% –33.9%) and NPV = 97.4% (96.4% –98.4%), LR+ = 3.7 (3.4–4.0) and LR− = 0.24 (0.2–0.4). Conclusion The proposed scoring system (with new scores) presented a good capacity for discriminating patients who did not have pulmonary TB, in the studied population. Further studies are necessary in order to validate it, thus permitting the assessment of its use in diagnosing smear-negative pulmonary TB in HIV-infected adults. PMID:24755628

  12. Proline-rich tyrosine kinase 2 downregulates peroxisome proliferator-activated receptor gamma to promote hypoxia-induced pulmonary artery smooth muscle cell proliferation.

    PubMed

    Bijli, Kaiser M; Kang, Bum-Yong; Sutliff, Roy L; Hart, C Michael

    2016-06-01

    Hypoxia stimulates pulmonary hypertension (PH), in part by increasing the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) via sustained activation of mitogen-activated protein kinase, extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and nuclear factor-kappa B (NF-κB); elevated expression of NADPH oxidase 4 (Nox4); and downregulation of peroxisome proliferator-activated receptor gamma (PPARγ) levels. However, the upstream mediators that control these responses remain largely unknown. We hypothesized that proline-rich tyrosine kinase 2 (Pyk2) plays a critical role in the mechanism of hypoxia-induced HPASMC proliferation. To test this hypothesis, HPASMCs were exposed to normoxia or hypoxia (1% O2) for 72 hours. Hypoxia activated Pyk2 (detected as Tyr402 phosphorylation), and inhibition of Pyk2 with small interfering RNA (siRNA) or tyrphostin A9 attenuated hypoxia-induced HPASMC proliferation. Pyk2 inhibition attenuated ERK 1/2 activation as early as 24 hours after the onset of hypoxia, suggesting a proximal role for Pyk2 in this response. Pyk2 inhibition also attenuated hypoxia-induced NF-κB activation, reduced HPASMC PPARγ messenger RNA levels and activity, and increased NF-κB-mediated Nox4 levels. The siRNA-mediated PPARγ knockdown enhanced Pyk2 activation, whereas PPARγ overexpression reduced Pyk2 activation in HPASMCs, confirming a reciprocal relationship between Pyk2 and PPARγ. Pyk2 depletion also attenuated hypoxia-induced NF-κB p65 activation and reduced PPARγ protein levels in human pulmonary artery endothelial cells. These in vitro findings suggest that Pyk2 plays a central role in the proliferative phenotype of pulmonary vascular wall cells under hypoxic conditions. Coupled with recent reports that hypoxia-induced PH is attenuated in Pyk2 knockout mice, these findings suggest that Pyk2 may represent a novel therapeutic target in PH. PMID:27252847

  13. Proline-rich tyrosine kinase 2 downregulates peroxisome proliferator–activated receptor gamma to promote hypoxia-induced pulmonary artery smooth muscle cell proliferation

    PubMed Central

    2016-01-01

    Abstract Hypoxia stimulates pulmonary hypertension (PH), in part by increasing the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) via sustained activation of mitogen-activated protein kinase, extracellular signal–regulated kinases 1 and 2 (ERK 1/2), and nuclear factor-kappa B (NF-κB); elevated expression of NADPH oxidase 4 (Nox4); and downregulation of peroxisome proliferator–activated receptor gamma (PPARγ) levels. However, the upstream mediators that control these responses remain largely unknown. We hypothesized that proline-rich tyrosine kinase 2 (Pyk2) plays a critical role in the mechanism of hypoxia-induced HPASMC proliferation. To test this hypothesis, HPASMCs were exposed to normoxia or hypoxia (1% O2) for 72 hours. Hypoxia activated Pyk2 (detected as Tyr402 phosphorylation), and inhibition of Pyk2 with small interfering RNA (siRNA) or tyrphostin A9 attenuated hypoxia-induced HPASMC proliferation. Pyk2 inhibition attenuated ERK 1/2 activation as early as 24 hours after the onset of hypoxia, suggesting a proximal role for Pyk2 in this response. Pyk2 inhibition also attenuated hypoxia-induced NF-κB activation, reduced HPASMC PPARγ messenger RNA levels and activity, and increased NF-κB-mediated Nox4 levels. The siRNA-mediated PPARγ knockdown enhanced Pyk2 activation, whereas PPARγ overexpression reduced Pyk2 activation in HPASMCs, confirming a reciprocal relationship between Pyk2 and PPARγ. Pyk2 depletion also attenuated hypoxia-induced NF-κB p65 activation and reduced PPARγ protein levels in human pulmonary artery endothelial cells. These in vitro findings suggest that Pyk2 plays a central role in the proliferative phenotype of pulmonary vascular wall cells under hypoxic conditions. Coupled with recent reports that hypoxia-induced PH is attenuated in Pyk2 knockout mice, these findings suggest that Pyk2 may represent a novel therapeutic target in PH. PMID:27252847

  14. Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis

    PubMed Central

    Vanikar, A.V.; Patel, R.D.; Suthar, K. S.; Trivedi, H. L.

    2016-01-01

    Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID:26894074

  15. Markers of Thrombogenesis and Fibrinolysis and Their Relation to Inflammation and Endothelial Activation in Patients with Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Kopeć, Grzegorz; Moertl, Deddo; Steiner, Sabine; Stępień, Ewa; Mikołajczyk, Tomasz; Podolec, Jakub; Waligóra, Marcin; Stępniewski, Jakub; Tomkiewicz-Pająk, Lidia; Guzik, Tomasz; Podolec, Piotr

    2013-01-01

    Background Chronic anticoagulation is a standard of care in idiopathic pulmonary arterial hypertension (IPAH). However, hemostatic abnormalities in this disease remain poorly understood. Therefore, we aimed to study markers of thrombogenesis and fibrinolysis in patients with IPAH. Methods We studied 27 consecutive patients (67% female) with IPAH aged 50.0 years (IQR: 41.0 - 65.0) and 16 controls without pulmonary hypertension. Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complexes were measured to assess thrombogenesis; tissue-type plasminogen activator (tPA) antigen and plasmin-anti-plasmin complex to characterize activation of fibrinolysis; plasminogen activator inhibitor 1 (PAI-1) to measure inhibition of fibrinolysis; and endothelin-1 (ET-1) and interleukin-6 (IL-6) to assess endothelial activation and systemic inflammation, respectively. In addition, in treatment-naive IPAH patients these markers were assessed after 3 months of PAH-specific therapies. Results TPA (10.1[6.8-15.8] vs 5.2[3.3-7.3] ng/ml, p<0.001), plasmin-anti-plasmin (91.5[60.3-94.2] vs 55.8[51.1-64.9] ng/ml, p<0.001), IL-6 (4.9[2.5-7.9] vs 2.1[1.3-3.8] pg/ml, p=0.001) and ET-1 (3.7 [3.3-4.5] vs 3.4[3.1-3.5], p= 0.03) were higher in patients with IPAH than in controls. In IPAH patients plasmin-anti-plasmin and tPA correlated positively with IL-6 (r=0.39, p=0.04 and r=0.63, p<0.001, respectively) and ET-1 (r=0.55, p=0.003 and r=0.59, p=0.001, respectively). No correlation was found between tPA or plasmin-anti-plasmin and markers of thrombogenesis. Plasmin-anti-plasmin decreased after 3 months of PAH specific therapy while the other markers remained unchanged. Conclusions In the present study we showed that markers of fibrynolysis were elevated in patients with IPAH however we did not find a clear evidence for increased thrombogenesis in this group of patients. Fibrinolysis, inflammation, and endothelial activation were closely interrelated in IPAH. PMID:24312667

  16. Pulmonary rehabilitation.

    PubMed

    Troosters, Thierry; Demeyer, Heleen; Hornikx, Miek; Camillo, Carlos Augusto; Janssens, Wim

    2014-03-01

    Pulmonary rehabilitation is a therapy that offers benefits to patients with chronic obstructive pulmonary disease that are complementary to those obtained by pharmacotherapy. The main objective of pulmonary rehabilitation is to restore muscle function and exercise tolerance, reverse other nonrespiratory consequences of the disease, and help patients to self-manage chronic obstructive pulmonary disease and its exacerbations and symptoms. To do so, a multidisciplinary program tailored to the patient in terms of program content, exercise prescription, and setting must be offered. Several settings and programs have shown to spin off in significant immediate results. The challenge lies in maintaining the benefits outside the program. PMID:24507849

  17. Risk Factors for Multidrug-Resistant Tuberculosis among Patients with Pulmonary Tuberculosis at the Central Chest Institute of Thailand

    PubMed Central

    Chuchottaworn, Charoen; Thanachartwet, Vipa; Sangsayunh, Piamlarp; Than, Thu Zar Myint; Sahassananda, Duangjai; Surabotsophon, Manoon; Desakorn, Varunee

    2015-01-01

    There are limited data available on the risk factors for multidrug-resistant tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case−control study among adults with pulmonary TB who received treatment at the Central Chest Institute of Thailand (CCIT) between January 2007 and December 2013, in order to determine the risk factors associated with MDR-TB among patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB (cases) and 145 patients with drug-sensitive pulmonary TB (controls). Multivariate analysis identified the independent risk factors for MDR-TB as follows: (1) ≥ 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95% confidence interval (95% CI) 7.86−200.66), (2) duration of illness > 60 days (OR 3.08, 95% CI 1.52−6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI 4.64−36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89−7.73), and (5) presence of pleural effusion (OR 2.75, 95% CI 1.06−7.16). Prior pulmonary TB management with a non-category I regimen (P = 0.012) and having treatment failure or default as treatment outcomes (P = 0.036) were observed in a higher proportion among patients with MDR-TB. Particular characteristics of lung cavities, including the maximum diameter ≥ 30 mm (P < 0.001), the number of cavities ≥ 3 (P = 0.001), bilateral involvement (P < 0.001), and ≥ 2 lung zones involved (P = 0.001) were more commonly observed in patients with MDR-TB. In conclusion, these clinical factors and chest radiographic findings associated with MDR-TB among patients with pulmonary TB may help physicians to provide proper management of cases for prevention of the development and spread of MDR-TB in future. PMID:26444421

  18. Chronic hypoxia-induced upregulation of Ca2+-activated Cl- channel in pulmonary arterial myocytes: a mechanism contributing to enhanced vasoreactivity.

    PubMed

    Sun, Hui; Xia, Yang; Paudel, Omkar; Yang, Xiao-Ru; Sham, James S K

    2012-08-01

    Chronic hypoxic pulmonary hypertension (CHPH) is associated with altered expression and function of cation channels in pulmonary arterial smooth muscle cells (PASMCs), but little is known for anion channels. The Ca(2+)-activated Cl(-) channel (CaCC), recently identified as TMEM16A, plays important roles in pulmonary vascular function. The present study sought to determine the effects of chronic hypoxia (CH) on the expression and function of CaCCs in PASMCs, and their contributions to the vascular hyperreactivity in CHPH. Male Wistar rats were exposed to room air or 10% O(2) for 3–4 weeks to generate CHPH. CaCC current (I(CI.Ca)) elicited by caffeine-induced Ca(2+) release or by depolarization at a constant high [Ca(2+)](i) (500 or 750 nm) was significantly larger in PASMCs of CH rats compared to controls. The enhanced I(CI.Ca)) density in CH PASMCs was unrelated to changes in amplitude of Ca(2+) release, Ca(2+)-dependent activation, voltage-dependent properties or calcineurin-dependent modulation of CaCCs, but was associated with increased TMEM16A mRNA and protein expression. Maximal contraction induced by serotonin, an important mediator of CHPH, was potentiated in endothelium-denuded pulmonary arteries of CH rats. The enhanced contractile response was prevented by the CaCC blockers niflumic acid and T16A(inh)-A01, or by the L-type Ca(2+) channel antagonist nifedipine. The effects of niflumic acid and nifedipine were non-additive. Our results demonstrate for the first time that CH increases I(CI.Ca) density, which is attributable to an upregulation of TMEM16A expression in PASMCs. The augmented CaCC activity in PASMCs may potentiate membrane depolarization and L-type channel activation in response to vasoconstrictors and enhance pulmonary vasoreactivity in CHPH. PMID:22674716

  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. IL-27 and TGFβ mediated expansion of Th1 and adaptive regulatory T cells expressing IL-10 correlates with bacterial burden and disease severity in pulmonary tuberculosis

    PubMed Central

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

    2015-01-01

    CD4+ T cell expression of IL-10 is an important mechanism controlling immunity to tuberculosis (TB). To identify the CD4+ T cell subsets producing IL-10 in human TB, we enumerated the frequencies of IL-10 expressing CD4+ T cell subsets following TB—antigen stimulation of cells from individuals with pulmonary (PTB) and latent TB (LTB). We first demonstrate that TB antigens induce an expansion of IL-10 expressing Th1 (IL-10+, IFNγ+, T-bet+), Th2 (IL-10+, IL-4+, GATA-3+), Th9 (IL-10+, IL-9+, IL-4−), Th17 (IL-10+, IL-17+, IFNγ−), and natural and adaptive regulatory T cells [nTregs; IL-10+, CD4+, CD25+, Foxp3+ and aTregs; IL-10 single+, CD4+, CD25−, Foxp3−] in PTB and LTB individuals, with frequencies being significantly higher in the former. However, only Th1 cells and adaptive Tregs expressing IL-10 exhibit a positive relationship with bacterial burdens and extent of disease in PTB. Finally, we show that IL-27 and TGFβ play an important role in the regulation of IL-10+ Th cell subsets. Thus, active PTB is characterized by an IL-27 and TGFβ mediated expansion of IL-10 expressing CD4+ T cell subsets, with IL-10+ Th1 and IL-10+ aTreg cells playing a potentially pivotal role in the pathogenesis of active disease. PMID:26417443

  1. 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

    2013-08-01

    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. PMID:23785711

  2. Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia.

    PubMed

    Guan, Yi-Fu; Song, Xun; Qiu, Ming-Hua; Luo, Shi-Hong; Wang, Bao-Jie; Van Hung, Nguyen; Cuong, Nguyen M; Soejarto, Djaja Doel; Fong, Harry H S; Franzblau, Scott G; Li, Sheng-Hong; He, Zhen-Dan; Zhang, Hong-Jie

    2016-08-01

    Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 μm in MABA assay, respectively, and 91.7 and 168.3 μm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 μm in MABA assay and 100.2 μm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives. PMID:26992112

  3. Making pulmonary rehabilitation a success in COPD.

    PubMed

    Bourbeau, J

    2010-01-01

    A truly successful pulmonary rehabilitation entails implementing physical activity maintenance. This article reviews the current knowledge on pulmonary rehabilitation and the expected benefits, the setting, the relationship between self-management and pulmonary rehabilitation, in order to develop and implement clinically-effective physical activity maintenance interventions. The effectiveness of pulmonary rehabilitation is well-established. However, access to pulmonary rehabilitation is limited. Home-based pulmonary rehabilitation has been shown to be an effective, equivalent alternative to outpatient pulmonary rehabilitation in COPD patients. The opportunity to offer different pulmonary rehabilitation settings tailored to individual needs should improve accessibility to this intervention. Sustained long-term physical activity remains the most important challenge for COPD patients. We need a dependable system of coordinated health care interventions and communication, and components that include self-management support. Self-management should be an integrated part of pulmonary rehabilitation and remain long after the pulmonary rehabilitation is completed. By early identification of patients who may have difficulty maintaining exercise and implementing appropriate self-management interventions during and after the rehabilitation program, it may be possible to promote better long-term involvement in physical activity. Pulmonary rehabilitation should not stand alone; the best program is that which can be maintained to translate into a continuous increase in the activities of daily living. Future research should evaluate the effect of self-management interventions combined with pulmonary rehabilitation to improve long-term activity and exercise maintenance. PMID:20809435

  4. Endogenous plasma activated protein C levels and the effect of enoxaparin and drotrecogin alfa (activated) on markers of coagulation activation and fibrinolysis in pulmonary embolism

    PubMed Central

    2011-01-01

    Introduction There are no published data on the status of endogenous activated protein C (APC) in pulmonary embolism (PE), and no data on the effect of drotrecogin alfa (activated) (DAA) given in addition to therapeutic dose enoxaparin. Methods In this double-blind clinical trial, 47 patients with computed tomography (CT)-confirmed acute submassive PE treated with 1 mg/kg body weight of enoxaparin twice daily were randomized to groups receiving a 12-hour intravenous infusion of 6, 12, 18, or 24 μg/kg/hour of DAA or a placebo. Blood samples were drawn before starting DAA infusion, after 4, 8 and 12 hours (at the end of the infusion period), and on treatment days 2, 3, 4, 5 and 6. Results Initial endogenous plasma activated protein C (APC) levels were 0.36 ± 0.48 ng/ml (<0.10 to 1.72 ng/ml) and remained in the same range in the placebo group. APC levels in patients treated with DAA were 13.67 ± 3.57 ng/ml, 32.71 ± 8.76 ng/ml, 36.13 ± 7.60 ng/ml, and 51.79 ± 15.84 ng/ml in patients treated with 6, 12, 18, and 24 μg/kg/hour DAA, respectively. In patients with a D-dimer level >4 mg/L indicating a high level of acute fibrin formation and dissolution, DAA infusion resulted in a more rapid drop in soluble fibrin, D-dimer, and fibrinogen/fibrin degradation products (FDP) levels, compared to enoxaparin alone. There was a parallel decline of soluble fibrin, D-dimer, FDP, and plasmin-plasmin inhibitor complex (PPIC) in response to treatment with enoxaparin ± DAA, with no evidence of a systemic profibrinolytic effect of the treatment. Conclusions In patients with acute submassive PE endogenous APC levels are low. DAA infusion enhances the inhibition of fibrin formation. Trial registration ClinicalTrials.gov: NCT00191724 PMID:21241489

  5. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    PubMed Central

    Drath, D B

    1985-01-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumoricidal activity against syngeneic and xenogeneic target cells. The pattern of metabolic activation of in situ tissue-associated macrophages differed somewhat from that of alveolar macrophages and was observed only after subsequent exposure of the cells to either zymosan particles or phorbol myristate acetate. Upon such exposure, the activated zymosan-treated tissue macrophages released approximately twice as much superoxide as the nonactivated cells and amounts comparable to the amounts released by activated alveolar macrophages. The tissue macrophages also displayed greater levels of cytotoxicity toward xenogenic targets than the alveolar cells and may have an important role in preventing microbial or tumor cell colonization of respiratory systems. PMID:2989181

  6. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    PubMed

    Drath, D B

    1985-07-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumoricidal activity against syngeneic and xenogeneic target cells. The pattern of metabolic activation of in situ tissue-associated macrophages differed somewhat from that of alveolar macrophages and was observed only after subsequent exposure of the cells to either zymosan particles or phorbol myristate acetate. Upon such exposure, the activated zymosan-treated tissue macrophages released approximately twice as much superoxide as the nonactivated cells and amounts comparable to the amounts released by activated alveolar macrophages. The tissue macrophages also displayed greater levels of cytotoxicity toward xenogenic targets than the alveolar cells and may have an important role in preventing microbial or tumor cell colonization of respiratory systems. PMID:2989181

  7. 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...

  8. 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

  9. Synchrotron and laser excitation of luminescence in PbWO4:Tb crystals at different temperatures

    NASA Astrophysics Data System (ADS)

    Novosad, S. S.; Kostyk, L. V.; Novosad, I. S.

    2011-09-01

    The effect of temperature on the spectral luminescence characteristics of PbWO4:Tb3+ crystals with synchrotron and laser excitation is studied. If PbWO4:Tb3+ is excited by synchrotron radiation with λ = 88 nm at 300 K, a faint recombination luminescence of the impurity terbium is observed against the matrix luminescence. When the temperature is reduced to 8 K, the luminescence intensity of PbWO4:Tb3+ increases by roughly an order of magnitude and the characteristic luminescence of the unactivated crystal is observed. Excitation of PbWO4:Tb3+ by a nitrogen laser at 300 K leads to the appearance of emission from Tb3+ ions. At 90 K, a faint matrix luminescence is observed in addition to the activator emission. The formation of the luminescence excitation spectra for wavelengths of 60-320 nm is analyzed and the nature of the emission bands is discussed.

  10. 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. PMID:25953850

  11. TB vaccine development and the End TB Strategy: importance and current status

    PubMed Central

    Fletcher, Helen A.; Schrager, Lewis

    2016-01-01

    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. PMID:27076508

  12. 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. PMID:27076508

  13. Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary vasoconstriction: evidence against a role for platelet-activating factor.

    PubMed

    McCormack, D G; Crawley, D E; Barnes, P J; Evans, T W

    1992-03-01

    1. The role of platelet-activating factor in the attenuated hypoxic pulmonary vasoconstriction associated with lung injury was evaluated using specific platelet-activating factor antagonists and an isolated perfused lung preparation. 2. Intratracheal bleomycin was administered to rats to produce acute lung injury. Animals received intratracheal saline (control), intratracheal bleomycin or the platelet-activating factor antagonists BN 52021, WEB 2170 or WEB 2086 before and after bleomycin treatment. Forty-eight hours after intratracheal administration of bleomycin or saline the animals were killed. 3. The increases in pulmonary artery pressure during two periods of hypoxic ventilation and in response to 0.2 microgram of angiotensin II were measured. Acetylcholine-induced vasodilatation after pre-constriction with prostaglandin F2 alpha was also measured. To quantify lung injury, the wet/dry ratio of lung weight was determined. 4. Bleomycin treatment attenuated the first and second hypoxic pressor responses by 93% and 77%, respectively, but not the pressor response to angiotensin II nor the vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the first hypoxic pressor response compared with bleomycin treatment alone, but the structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB 2086 had no significant effect on the bleomycin-induced attenuation of hypoxic pulmonary vasoconstriction. None of the platelet-activating factor antagonists blocked the increase in the wet/dry lung weight ratio induced by bleomycin. 5. Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary vasoconstriction, an effect that does not appear to be mediated by platelet-activating factor. The mechanism remains to be elucidated, but may involve destruction of the hypoxic 'sensor' within the respiratory tract. PMID:1372199

  14. Activity of Ca2+ -activated Cl- channels contributes to regulating receptor- and store-operated Ca2+ entry in human pulmonary artery smooth muscle cells

    PubMed Central

    Yamamura, Aya; Yamamura, Hisao; Zeifman, Amy; Yuan, Jason X.-J.

    2011-01-01

    Intracellular Ca2+ plays a fundamental role in regulating cell functions in pulmonary arterial smooth muscle cells (PASMCs). A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) triggers pulmonary vasoconstriction and stimulates PASMC proliferation. [Ca2+]cyt is increased mainly by Ca2+ release from intracellular stores and Ca2+ influx through plasmalemmal Ca2+-permeable channels. Given the high concentration of intracellular Cl- in PASMCs, Ca2+-activated Cl-(ClCa) channels play an important role in regulating membrane potential and cell excitability of PASMCs. In this study, we examined whether activity of ClCa channels was involved in regulating [Ca2+]cyt in human PASMCs via regulating receptor- (ROCE) and store- (SOCE) operated Ca2+ entry. The data demonstrated that an angiotensin II (100 nM)-mediated increase in [Ca2+]cyt via ROCE was markedly attenuated by the ClCa channel inhibitors, niflumic acid (100 μM), flufenamic acid (100 μM), and 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (100 μM). The inhibition of ClCa channels by niflumic acid and flufenamic acid significantly reduced both transient and plateau phases of SOCE that was induced by passive depletion of Ca2+ from the sarcoplasmic reticulum by 10 μM cyclopiazonic acid. In addition, ROCE and SOCE were abolished by SKF-96365 (50 μM) and 2-aminoethyl diphenylborinate (100 μM), and were slightly decreased in the presence of diltiazem (10 μM). The electrophysiological and immunocytochemical data indicate that ClCa currents were present and TMEM16A was functionally expressed in human PASMCs. The results from this study suggest that the function of ClCa channels, potentially formed by TMEM16A proteins, contributes to regulating [Ca2+]cyt by affecting ROCE and SOCE in human PASMCs. PMID:22034612

  15. 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.

  16. 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

  17. 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

  18. DIAGNOSTIC TEST OF SPUTUM GENEXPERT MTB/RIF FOR SMEAR NEGATIVE PULMONARY TUBERCULOSIS.

    PubMed

    Reechaipichitkul, Wipa; Phetsuriyawong, Attawoot; Chaimanee, Prajuab; Ananta, Pimjai

    2016-05-01

    The objective of this study was to evaluate the performance of the Gene-Xpert MTB/RIF sputum test for diagnosing pulmonary tuberculosis (TB) among patients sputum acid-fast bacillus (AFB) smear negative results in Thailand, a country with a high prevalence of pulmonary tuberculosis. We studied 151 patients who presented to Srinagarind Hospital, Khon Kaen, Thailand with a 2 week or more history of fever and/or cough and an abnormal chest radiograph between 2010 and 2014; these patients had at least 2 negative sputum AFB smear results. Of these, 76 were diagnosed as having either confirmed or probable pulmonary TB: the 32 confirmed cases were those with a positive sputum culture for Mycobacterium tuberculosis (MTB) and the 44 probable case were those with clinical and radiographic findings consistent with TB and who had a response to anti-TB therapy. Seventy-five cases were diagnosed as not having pulmonary TB. Of the 32 patients with a positive sputum culture for MTB, 26 had a positive GeneXpert MTB/RIF sputum test. Compared to sputum culture for MTB the GeneXpert MTB/ RIF test gave a sensitivity of 83.9% (95% CI: 66.3-94.5) and a specificity of 92.1% (95% CI: 83.6-97), a positive predictive value (PPV) of 81.3% (95% CI: 63.6-92.8) and a negative predictive value (NPV) of 93.3% (95% CI: 85.1-97.8). The GeneXpert MTB/RIF test had a fair sensitivity and specificity for diagnosing smear negative pulmonary TB. It may be useful for diagnosing pulmonary TB in patients with a negative sputum AFB smear. The assay is faster than culture and can detect rifampicin resistant strains of MTB. PMID:27405129

  19. Platelet-activating factor-induced pulmonary edema is partly mediated by prostaglandin E(2), E-prostanoid 3-receptors, and potassium channels.

    PubMed

    Göggel, Rolf; Hoffman, Sven; Nüsing, Rolf; Narumiya, Suh; Uhlig, Stefan

    2002-09-01

    Platelet-activating factor (PAF) is an important endogenous mediator of pulmonary edema in many models of acute lung injury. PAF triggers edema formation by simultaneous activation of two independent pathways; one is mediated by a cyclooxygenase metabolite, and the other is blocked by quinine. We examined the hypothesis that the cyclooxygenase-dependent part of PAF-induced edema is mediated by prostaglandin E(2) (PGE(2)). In isolated rat lungs, PAF administration stimulated release of PGE(2) into the venous effluate and increased lung weight as a measure of edema formation. Perfusion with a neutralizing PGE(2) antibody attenuated the PAF-induced edema formation. In vivo, E-prostanoid 3-receptor-deficient mice showed less pulmonary Evans blue extravasation in response to PAF injection than did mice deficient in EP1, EP2, or EP4 receptors. Perfusion of rat lungs with PGE(2) caused pulmonary edema, which was largely prevented by inhibition of voltage-gated potassium channels (25 nM beta-dendrotoxin), but not by blocking calcium-dependent potassium currents (100 micro M paxilline). In line with its effects on PGE(2)-induced edema formation, beta-dendrotoxin attenuated PAF-induced edema partly if given alone, and completely in combination with quinine. Our findings suggest that PAF-triggered edema is partly mediated by the release of PGE(2), activation of EP3 receptors, and activation of voltage-gated potassium channels. PMID:12204861

  20. They can't bury you while you're still moving: A review of the European Respiratory Society statement on physical activity in chronic obstructive pulmonary disease.

    PubMed

    Nici, Linda; ZuWallack, Richard

    2015-01-01

    Physical activity (PA) and exercise are interrelated but separate concepts. PA refers to bodily movement produced by skeletal muscles that results in energy expenditure. Exercise is a subset of PA, in which generally higher levels of muscular activity are performed for a purpose, such as achieving physical fitness or winning a sporting contest. Higher exercise capacity is considered to be permissive of greater PA in the home and community settings. Individuals with chronic obstructive pulmonary disease (COPD) are physically inactive when compared with healthy age-matched control subjects. Furthermore, physical inactivity is independently associated with adverse outcome in patients with COPD, including more rapid disease progression, impaired health status, and increased health care utilization and mortality risk. While there are several methods to objectively measure PA, recent scientific studies have commonly utilized questionnaires and activity monitors. The latter include simple pedometers and complex accelerometers, which can measure and record movement in up to 3 planes. In COPD, multiple patient characteristics and disease severity markers are related to activity level, including pulmonary physiological abnormalities such as airway obstruction and hyperinflation; exercise capacity such as the 6-minute walking distance; exacerbations of respiratory disease; and comorbid conditions. Clinical trials of bronchodilators, supplemental oxygen therapy, exercise training or pulmonary rehabilitation, or PA counseling have provided inconsistent results in demonstrating increased PA from the interaction. This is probably because the phenomenon of physical inactivity is complex, resulting not only from physiological impairments, but symptoms, cultural, motivational, and environmental factors. PMID:26307102

  1. 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

  2. [The intervention against an outbreak of pulmonary tuberculosis in the dormitory of construction laborers--Connection with approaches from public health, medical treatment, social welfare, and labor management].

    PubMed

    Iburi, S; Fujita, J; Yajima, H; Kakuda, H; Sakamoto, M; Matsumura, A

    2001-11-01

    An outbreak of pulmonary tuberculosis (TB) in a dormitory of construction laborers took place, and this outbreak was presumed to be caused by the same sourse of infection, based on the results of restriction fragment length polymorphism (RFLP) analysis and other findings. After the first patient was admitted to the hospital with active TB, 18 new other TB patients were discovered by repeated contacts examinations. They were all male and single, and were aged from 41 to 67 years old (mean age 51.7). Among 19 patients, only 4 patients had a health insurance. As these patients lived together in the same dormitory, to prevent infection through close contact in the dormitory, repeated contacts examinations were further performed. In addition, several medical, social, and economical interventions were needed for these patients. It was also required to improve labor conditions in this construction company. It was concluded that comprehensive approaches including public health, medical treatment, social welfare, and labor management aspects were indispensable to prevent TB among relatively poor laborers. PMID:11766360

  3. Why healthcare workers are sick of TB.

    PubMed

    von Delft, Arne; Dramowski, Angela; Khosa, Celso; Kotze, Koot; Lederer, Philip; Mosidi, Thato; Peters, Jurgens A; Smith, Jonathan; van der Westhuizen, Helene-Mari; von Delft, Dalene; Willems, Bart; Bates, Matthew; Craig, Gill; Maeurer, Markus; Marais, Ben J; Mwaba, Peter; Nunes, Elizabete A; Nyirenda, Thomas; Oliver, Matt; Zumla, Alimuddin

    2015-03-01

    Dr Thato Mosidi never expected to be diagnosed with tuberculosis (TB), despite widely prevalent exposure and very limited infection control measures. The life-threatening diagnosis of primary extensively drug-resistant TB (XDR-TB) came as an even greater shock. The inconvenient truth is that, rather than being protected, Dr Mosidi and thousands of her healthcare colleagues are at an increased risk of TB and especially drug-resistant TB. In this viewpoint paper we debunk the widely held false belief that healthcare workers are somehow immune to TB disease (TB-proof) and explore some of the key factors contributing to the pervasive stigmatization and subsequent non-disclosure of occupational TB. Our front-line workers are some of the first to suffer the consequences of a progressively more resistant and fatal TB epidemic, and urgent interventions are needed to ensure the safety and continued availability of these precious healthcare resources. These include the rapid development and scale-up of improved diagnostic and treatment options, strengthened infection control measures, and focused interventions to tackle stigma and discrimination in all its forms. We call our colleagues to action to protect themselves and those they care for. PMID:25809771

  4. TB an epidemic in Russia's prisons.

    PubMed

    1999-01-01

    Over 100,000 prisoners are infected with tuberculosis (TB) in Russia, which has the highest incarceration rate in the world. Drug-resistant TB is found in thousands of inmates, and approximately 20,000 have died from it within the past 2 years. Although the country now has 50 centers for TB-infected prisoners, many are not being cured because of medicine shortages and failure to complete treatment. Up to 25 percent of TB infections found in Russian jails are multi-drug resistant, as opposed to 4 percent in Russia's general population and under 2 percent in the United States. PMID:11367347

  5. 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. PMID:27108702

  6. Validity and Usability of Physical Activity Monitoring in Patients with Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    Nell, Christoph; Storre, Jan Hendrik; Windisch, Wolfram; Magerhans, Lena; Beutel, Bjoern; Kenn, Klaus; Greulich, Timm; Alter, Peter; Vogelmeier, Claus; Koczulla, Andreas Rembert

    2016-01-01

    Background A large proportion of COPD patients do not achieve the recommended level of physical activity. It is suggested that feedback on the level of activity by using an activity monitoring device (PAM) increases awareness and may stimulate patients to increase their physical activity in daily life. Our objective was to assess the validity and usability of a simple and low-cost physical activity monitor (Polar A300™) when compared with the validated and established Bodymedia-SenseWear™ (SWA) device. Methods To assess the diagnostic equivalent, two different PAM devices were used in parallel in 20 COPD patients GOLD I to IV during 3 consecutive days of daily life. Both systems were compared in terms of steps, calories burned, daily activity time and metabolic equivalents using linear regression analysis and Bland-Altman plots. Practical usability was examined by a 16-item-questionnaire. Results High correlations of both devices were observed with regard to the sensed step count (r = 0.96; p < 0.01) and calories burned (r = 0.74; p < 0.01), and a lower correlation of daily activity (r = 0.25; p < 0.01) was found. Data analysis over 3 days showed that 90% of the steps (95% CI -4223 to 1887), 100% of the calories (95% CI -2798 to 1887), 90% of the daily activity data (95% CI -12.32, 4065) and 95% of the MET (95% CI -3.11 to 2.75) were within the limits of agreement. A favorable usability (system-, information- and interface quality) of the A300™ device was shown (p < 0.01). Conclusion The A300™ device with easy practical usability was shown not to be inferior for assessment of physical activity time, step count and calorie consumption in COPD patients when compared with the SWA. It is suggested to consider widespread available devices as commonly used for monitoring recreational sporting activities also in patients for assessment of physical activity in daily life. PMID:27305105

  7. Microbiome diversity in the sputum of patients with pulmonary tuberculosis.

    PubMed

    Krishna, P; Jain, A; Bisen, P S

    2016-07-01

    TB is a worldwide pandemic. India has the highest burden of TB, with WHO statistics for 2013 giving an estimated incidence figure of 2.1 million cases for India out of a global incidence of 9 million. Microbiota have been shown to be associated with many disease conditions; however, only few studies have been reported for microbiota associated with TB infection. For the first time, we characterized the composition of microbiota of TB patients of India, using high-throughput 16S rRNA gene sequencing and compared it with healthy controls. Phylum-level analysis showed that the relative abundance of Firmicutes and Actinobacteria was significantly higher in TB samples and Neisseria and Veillonella were two dominant genera after Streptococcus. In our study, significantly different core genera in TB and normal population were found as compared with the reported studies. Also, the presence of diverse opportunistic pathogenic microbiota in TB patients increases the complexity and diversity of sputum microbiota. Characterization of the sputum microbiome is likely to provide important pathogenic insights into pulmonary tuberculosis. PMID:27142586

  8. Encapsulation of beraprost sodium in nanoparticles: analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension.

    PubMed

    Ishihara, Tomoaki; Hayashi, Erika; Yamamoto, Shuhei; Kobayashi, Chisa; Tamura, Yuichi; Sawazaki, Ryoichi; Tamura, Fumiya; Tahara, Kayoko; Kasahara, Tadashi; Ishihara, Tsutomu; Takenaga, Mitsuko; Fukuda, Keiichi; Mizushima, Tohru

    2015-01-10

    Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer. The accumulation of nanoparticles in damaged pulmonary arteries was examined using fluorescence-emitting rhodamine S-encapsulated nanoparticles. The monocrotaline-induced PAH rat model and the hypoxia-induced mouse model were used to examine the pharmacological activity of BPS-encapsulated nanoparticles. A nanoparticle, named BPS-NP, was selected among various types of BPS-encapsulated nanoparticles tested; this was based on the sustained release profile in vitro and blood clearance profile in vivo. Fluorescence-emitting rhodamine S-encapsulated nanoparticles were prepared in a similar manner to that of BPS-NP, and showed accumulation and prolonged residence in monocrotaline-damaged pulmonary peripheral arteries. Intravenous administration of BPS-NP (once per week, 20μg/kg) protected against monocrotaline-induced pulmonary arterial remodeling and right ventricular hypertrophy. The extent of this protection was similar to that observed with oral administration (once per day, 100μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20μg/kg) also exhibited an ameliorative effect on hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy. The beneficial effects of BPS-NP on PAH animal models seem to be mediated by its sustained release and tissue targeting profiles. BPS-NP may be useful for the treatment of PAH patients due to reduced dosages and frequency of BPS administration. PMID:25449809

  9. Soluble Guanylate Cyclase Stimulators and Activators: Novel Therapies for Pulmonary Vascular Disease or a Different Method of Increasing cGMP?

    PubMed

    Koress, Cody; Swan, Kevin; Kadowitz, Philip

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a progressively worsening disorder characterized by increased pulmonary vascular resistance leading to increased afterload, right ventricular hypertrophy, and ultimately right heart failure and death. Current pharmacologic treatments primarily act to reduce pulmonary vascular resistance (PVR) and provide some benefit but do not cure PAH. Canonical vasodilator therapy involving the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP pathway has demonstrated efficacy, but in pathologic states, endothelial dysfunction within the pulmonary vasculature leads to the reduced synthesis and bioavailability of NO. Acting downstream of NO, sGC stimulators and activators restore the endogenous functions of NO and exploit the positive effects of sGC stimulation on various organ systems, including the heart. Riociguat (BAY 63-2521) is the first agent in a class of sGC stimulators to receive FDA approval for the treatment of PAH and chronic thromboembolic hypertension (CTEPH). Riociguat has demonstrated significant benefit as assessed by 6MWD, PVR, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, time to clinical worsening, World Health Organization (WHO) functional class, and other quality of life measures in clinical trials as a monotherapy and in combination with endothelin receptor antagonists or non-intravenous prostanoids. Riociguat is the first FDA-approved treatment option for inoperable or persistent CTEPH and adds a new effective drug to available treatment options for pulmonary hypertension (PH). The question of whether riociguat is superior to other available treatment options is unanswered at the present time and requires further study. PMID:27118316

  10. Identifying locations of recent TB transmission in rural Uganda: a multidisciplinary approach

    PubMed Central

    Chamie, Gabriel; Wandera, Bonnie; Marquez, Carina; Kato-Maeda, Midori; Kamya, Moses R.; Havlir, Diane V.; Charlebois, Edwin D.

    2015-01-01

    Objectives Targeting high TB transmission sites may offer a novel approach to TB prevention in sub-Saharan Africa. We sought to characterize TB transmission sites in a rural Ugandan township. Methods We recruited adults starting TB treatment in Tororo, Uganda over one year. 54 TB cases provided names of frequent contacts, sites of residence, health care, work and social activities, and two sputum samples. Mycobacterium tuberculosis (MTB) culture-positive specimens underwent spoligotyping to identify strains with shared genotypes. We visualized TB case social networks, and obtained, mapped and geo-coded global positioning system measures for every location that cases reported frequenting one month before treatment. Locations of spatial overlap among genotype-clustered cases were considered potential transmission sites. Results Six distinct genotypic clusters were identified involving 21/33(64%) MTB culture-positive, genotyped cases; none shared a home. Although 18/54(33%) TB cases shared social network ties, none of the genotype-clustered cases shared social ties. Using spatial analysis, we identified potential sites of within-cluster TB transmission for five of six genotypic clusters. All sites but one were health care and social venues, including sites of drinking, worship and marketplaces. Cases reported spending the largest proportion of pre-treatment person-time (22.4%) at drinking venues. Conclusions Using molecular epidemiology, geospatial and social network data from adult TB cases identified at clinics, we quantified person-time spent at high-risk locations across a rural Ugandan community, and determined the most likely sites of recent TB transmission to be health care and social venues. These sites may not have been identified using contact investigation alone. PMID:25583212

  11. [Spectra characteristics of LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphor].

    PubMed

    Wang, Zhi-Jun; Li, Pan-Lai; Yang, Zhi-Ping; Guo, Qing-Lin

    2009-11-01

    LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphors were synthesized by solid state reaction. The starting materials CaCO3, SrCO3, BaCO3, H3 BO3, Li2 CO3, Na2 CO3, K2 CO3 and Tb4 O7 (99.99% in mass) in appropriate stoichiometric ratio were mixed in the alumina crucible, then the mixed powders were calcined at 700 degrees C for 2 h, and LiCaBO3 : Tb3+, LiSrBO3 : Tb3+ and LiB-aBO3 : Tb3+ phosphors were obtained. The emission and excitation spectra were measured by a Shimadzu RF-540 ultraviolet spectrophotometer. All the photoluminescence properties of these phosphors were measured at room temperature. The emission spectra of LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphors show several bands, and the main emission peaks correspond to the 5D4 --> 7F6(486, 486, 488 nm), 5D4 --> F5 (544, 544, 544 nm), 5D4 --> 7F4 (590, 595, 593 nm) and 5D4 --> 7F3 (620, 620, 616 nm) typical transitions of Tb3+, and the typical transitions of Tb3+ happens to split because of the effects of LiM (M = Ca, Sr, Ba) BO3 crystals field. The excitation spectra for the 544 nm green emission of LiM (M = Ca, Sr, Ba)BO3 : Tb3+ phosphors illuminate that these kinds of phosphors can be effectively excited by ultraviolet (350-410 nm) light, and emit green light, therefore, they are promising phosphors for white light emitting diodes. Effects of activation and charge compensation on the luminescence intensities of LiM (M = Ca, Sr, Ba) BO3 : Tb3+ phosphors were studied, and the results show that the intensities were obviously effected. PMID:20101952

  12. 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. PMID:27317453

  13. 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

  14. 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

  15. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis See also: Aspergillosis Symptoms You may not have ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Update Date 8/31/2014 Updated by: Jatin ...

  16. Pulmonary Atresia

    MedlinePlus

    ... to repair the defect. Return to main topic: Congenital Heart Disease See on other sites: MedlinePlus https://medlineplus.gov/ency/article/001091.htm Pulmonary atresia American Heart Association www. ...

  17. 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

  18. Pulmonary atresia

    MedlinePlus

    ... form of heart disease that occurs from birth (congenital heart disease), in which the pulmonary valve does not form ... As with most congenital heart diseases, there is no known cause of ... is associated with another type of congenital heart defect ...

  19. Pulmonary Embolism

    MedlinePlus

    ... is a sudden blockage in a lung artery. The cause is usually a blood clot in the leg called a deep vein thrombosis that breaks loose and travels through the bloodstream to the lung. Pulmonary embolism is a ...

  20. 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

  1. Pulmonary cachexia.

    PubMed

    Schols, Annemie M W J

    2002-09-01

    Weight loss is a frequent complication in patients with chronic obstructive pulmonary disease (COPD) and is a determining factor of functional capacity, health status, and mortality. Weight loss in COPD is a consequence of increased energy requirements unbalanced by dietary intake. Both metabolic and mechanical inefficiency contribute to the elevated energy expenditure during physical activity, while systemic inflammation is a determinant of hypermetabolism at rest. A disbalance between protein synthesis and protein breakdown may cause a disproportionate depletion of fat-free mass in some patients. Nutritional support is indicated for depleted patients with COPD because it provides not only supportive care, but direct intervention through improvement in respiratory and peripheral skeletal muscle function and in exercise performance. A combination of oral nutritional supplements and exercise or anabolic stimulus appears to be the best treatment approach to obtaining significant functional improvement. Patients responding to this treatment even demonstrated a decreased mortality. Poor response was related to the effects of systemic inflammation on dietary intake and catabolism. The effectiveness of anticatabolic modulation requires further investigation. PMID:12163214

  2. Pulmonary Edema

    PubMed Central

    Tanser, Paul H.

    1980-01-01

    The physician who deals with pulmonary edema from a pathophysiologic basis will seldom make a diagnostic or therapeutic error. Recent additions to preload and afterload therapy have greatly helped in the emergency and ambulatory treatment of pulmonary edema due to left heart failure. Careful follow-up and patient self-monitoring are the most effective means of reducing hospitalization of chronic heart failure patients. PMID:21293700

  3. Oxidant-mediated activation of cytosolic phospholipase a(2) in pulmonary endothelium: role of protein kinase C alpha and a pertussis toxin-sensitive protein.

    PubMed

    Chakraborti, Sajal; Das, Sudip; Chakraborti, Tapati

    2005-01-01

    The authors have previously demonstrated that the oxidant t-buOOH stimulates phospholipase A(2) (PLA(2)) activity in bovine pulmonary artery endothelial cells (S. Chakraborti et al. American Journal of Physiology, 257, L430-L437, 1989). Herein, the authors sought to investigate the mechanism by which t-buOOH stimulates PLA(2) activity and the role of protein kinase C (PKC) in this scenario. Treatment of bovine pulmonary artery endothelial cells with t-buOOH stimulated an aprotinin-sensitive protease activity, PKC activity, and PLA(2) activity in the cell membrane. Pretreatment with intracellular Ca(2+) chelator (BAPTA-AM), PKCalpha inhibitor (Go6976), cPLA(2) inhibitor (AACOCF(3)), and pertussis toxin prevented t-buOOH-stimulated PLA(2) activity. Immunoblot studies with aprotinin, cPLA(2), PKCalpha, and Gialpha antibodies revealed their presence in the endothelial membrane. Immunoblot studies of the cell membrane isolated from t-buOOH-stimulated cells with cPLA(2) and PKCalpha antibodies elicited an apparent increase in their immunoreactive protein profiles along with an additional 47-kDa immunoreactive fragment in the membrane. t-buOOH caused Gialpha phosphorylation in the membrane and pretreatment with Go6976 prevented the phosphorylation. Overall, these results suggest that t-buOOH stimulates an aprotinin-sensitive protease activity that proteolytically activates PKCalpha and that subsequently phosphorylates a pertussis toxin-sensitive protein, resulting in the stimulation of cPLA(2) activity in the cell membrane. PMID:16291515

  4. The Influence of Smoking on Pulmonary Tuberculosis in Diabetic and Non-Diabetic Patients

    PubMed Central

    Bai, Kuan-Jen; Lee, Jen-Jyh; Chien, Shun-Tien; Suk, Chi-Won; Chiang, Chen-Yuan

    2016-01-01

    Background Both smoking and diabetes can increase the risk and influence the manifestations and outcomes of tuberculosis (TB). It is not clear whether the influence of smoking on pulmonary TB differs between non-diabetic and diabetic patients. Herein, we assessed the manifestations and outcomes of TB in relation to smoking in both diabetic and non-diabetic TB patients. Methodology/Principal Findings All diabetic culture-positive pulmonary TB patients notified from 2005–2010 at three teaching hospitals in Taiwan were enrolled. A culture-positive pulmonary TB patient without DM who was notified to the health authority immediately prior to each diabetic TB patient was selected for comparison. The 972 patients in this study cohort included 365 (37.6%) non-diabetic non-smokers, 149 (15.3%) non-diabetic smokers, 284 (29.2%) diabetic non-smokers, and 174 (17.9%) diabetic smokers. The adjusted relative risk of a pretreatment positive smear for a smoker compared with a non-smoker was 2.19 (95% CI 1.38–3.47) in non-diabetic patients and 2.23 (95% CI 1.29–3.87) in diabetic culture-positive pulmonary TB patients. The adjusted relative risk for a positive smear among diabetic smokers was 5.61 (95% CI 3.35–9.41) compared with non-diabetic non-smokers. Smoking was significantly associated with an increased frequency of bilateral lung parenchyma involvement (AdjOR 1.84, 95% CI 1.16–2.93), far-advanced pulmonary TB (AdjOR 1.91, 95% CI 1.04–3.50), cavitary lesions (AdjOR 2.03, 95% CI 1.29–3.20), and unfavorable outcomes of TB (AdjOR 2.35, 95% CI 1.02–5.41) in non-diabetic patients. However, smoking was not associated with cavitary lung parenchyma lesions regarding the location, number or size of the cavity in diabetic TB patients. Conclusions/Significance Smoking and diabetes have joint effects on a pretreatment positive smear. Diabetic smokers had more than a 5-fold increased risk of a pretreatment positive smear than did non-diabetic non-smokers, indicating

  5. 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. PMID:26677940

  6. Diagnostic value of antibody responses to multiple antigens from Mycobacterium tuberculosis in active and latent tuberculosis.

    PubMed

    Senoputra, Muhammad Andrian; Shiratori, Beata; Hasibuan, Fakhrial Mirwan; Koesoemadinata, Raspati Cundarani; Apriani, Lika; Ashino, Yugo; Ono, Kenji; Oda, Tetsuya; Matsumoto, Makoto; Suzuki, Yasuhiko; Alisjahbana, Bachti; Hattori, Toshio

    2015-11-01

    We investigated the antibody responses to 10 prospective Mycobacterium tuberculosis (MTB) antigens and evaluated their ability to discriminate between latent (LTBI) and active pulmonary tuberculosis (TB). Our results indicate that plasma levels of anti-α-crystallin (ACR), antilipoarabinomannan, anti-trehalose 6,6'-dimycolate, and anti-tubercular-glycolipid antigen antibodies were higher in patients with active TB, compared to those in the LTBI and control subjects. No differences in the antibodies were observed between the control and LTBI subjects. Antibodies against the glycolipid antigens could not distinguish between Mycobacterium avium complex (MAC)-negative TB patients and MAC-infected LTBI individuals. The most useful serological marker was antibodies to ACR, with MAC-negative TB patients having higher titers than those observed in MAC-positive LTBI and control subjects. Our data indicate that antibody to ACR is a promising target for the serological diagnosis of patients with active TB patients. When dealing with antiglycolipid antibodies, MAC coinfection should always be considered in serological studies. PMID:26307672

  7. Detection of differentially regulated subsarcolemmal calcium signals activated by vasoactive agonists in rat pulmonary artery smooth muscle cells

    PubMed Central

    Subedi, Krishna P.; Paudel, Omkar

    2013-01-01

    Intracellular calcium (Ca2+) plays pivotal roles in distinct cellular functions through global and local signaling in various subcellular compartments, and subcellular Ca2+ signal is the key factor for independent regulation of different cellular functions. In vascular smooth muscle cells, subsarcolemmal Ca2+ is an important regulator of excitation-contraction coupling, and nucleoplasmic Ca2+ is crucial for excitation-transcription coupling. However, information on Ca2+ signals in these subcellular compartments is limited. To study the regulation of the subcellular Ca2+ signals, genetically encoded Ca2+ indicators (cameleon), D3cpv, targeting the plasma membrane (PM), cytoplasm, and nucleoplasm were transfected into rat pulmonary arterial smooth muscle cells (PASMCs) and Ca2+ signals were monitored using laser scanning confocal microscopy. In situ calibration showed that the Kd for Ca2+ of D3cpv was comparable in the cytoplasm and nucleoplasm, but it was slightly higher in the PM. Stimulation of digitonin-permeabilized cells with 1,4,5-trisphosphate (IP3) elicited a transient elevation of Ca2+ concentration with similar amplitude and kinetics in the nucleoplasm and cytoplasm. Activation of G protein-coupled receptors by endothelin-1 and angiotensin II preferentially elevated the subsarcolemmal Ca2+ signal with higher amplitude in the PM region than the nucleoplasm and cytoplasm. In contrast, the receptor tyrosine kinase activator, platelet-derived growth factor, elicited Ca2+ signals with similar amplitudes in all three regions, except that the rise-time and decay-time were slightly slower in the PM region. These data clearly revealed compartmentalization of Ca2+ signals in the subsarcolemmal regions and provide the basis for further investigations of differential regulation of subcellular Ca2+ signals in PASMCs. PMID:24352334

  8. 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 ...

  9. A Broad Profile of Co-Dominant Epitopes Shapes the Peripheral Mycobacterium tuberculosis Specific CD8+ T-Cell Immune Response in South African Patients with Active Tuberculosis

    PubMed Central

    Axelsson-Robertson, Rebecca; Loxton, André G.; Walzl, Gerhard; Ehlers, Marthie M.; Kock, Marleen M.; Zumla, Alimuddin; Maeurer, Markus

    2013-01-01

    We studied major histocompatibility complex (MHC) class I peptide-presentation and nature of the antigen-specific CD8+ T-cell response from South African tuberculosis (TB) patients with active TB. 361 MHC class I binding epitopes were identified from three immunogenic TB proteins (ESAT-6 [Rv3875], Ag85B [Rv1886c], and TB10.4 [Rv0288], including amino acid variations for Rv0288, i.e., A10T, G13D, S27N, and A71S for MHC allotypes common in a South African population (e.g., human leukocyte antigen [HLA]-A*30, B*58, and C*07). Inter-allelic differences were identified regarding the broadness of the peptide-binding capacity. Mapping of frequencies of Mycobacterium tuberculosis (M. tb) antigen-specific CD8+ T-cells using 48 different multimers, including the newly constructed recombinant MHC class I alleles HLA-B*58:01 and C*0701, revealed a low frequency of CD8+ T-cell responses directed against a broad panel of co-dominant M. tb epitopes in the peripheral circulation of most patients. The antigen-specific responses were dominated by CD8+ T-cells with a precursor-like phenotype (CD45RA+CCR7+). The data show that the CD8+ T-cell response from patients with pulmonary TB (prior to treatment) is directed against subdominant epitopes derived from secreted and non-secreted M. tb antigens and that variant, natural occurring M. tb Rv0288 ligands, have a profound impact on T-cell recognition. PMID:23555576

  10. Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

    PubMed Central

    2014-01-01

    Background Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion. Methods & Results 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury. Conclusions Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress. PMID

  11. Predictors of Pulmonary Infarction

    PubMed Central

    Miniati, Massimo; Bottai, Matteo; Ciccotosto, Cesario; Roberto, Luca; Monti, Simonetta

    2015-01-01

    Abstract In the setting of acute pulmonary embolism (PE), pulmonary infarction is deemed to occur primarily in individuals with compromised cardiac function. The current study was undertaken to establish the prevalence of pulmonary infarction in patients with acute PE, and the relationship between infarction and: age, body height, body mass index (BMI), smoking habits, clot burden, and comorbidities. The authors studied prospectively 335 patients with acute PE diagnosed by computed tomographic angiography (CT) in 18 hospitals throughout central Italy. The diagnosis of pulmonary infarction on CT was based on Hampton and Castleman's criteria (cushion-like or hemispherical consolidation lying along the visceral pleura). Multivariable logistic regression was used to model the relationship between covariates and the probability of pulmonary infarction. The prevalence of pulmonary infarction was 31%. Patients with infarction were significantly younger and with significantly lower prevalence of cardiovascular disease than those without (P < 0.001). The frequency of infarction increased linearly with increasing height, and decreased with increasing BMI. In logistic regression, the covariates significantly associated with the probability of infarction were age, body height, BMI, and current smoking. The risk of infarction grew with age, peaked at approximately age 40, and decreased afterwards. Increasing body height and current smoking were significant amplifiers of the risk of infarction, whereas increasing BMI appeared to confer some protection. Our data indicate that pulmonary infarction occurs in nearly one-third of the patients with acute PE. Those with infarction are often young and otherwise healthy. Increasing body height and active smoking are predisposing risk factors. PMID:26469892

  12. Predictors of Pulmonary Infarction.

    PubMed

    Miniati, Massimo; Bottai, Matteo; Ciccotosto, Cesario; Roberto, Luca; Monti, Simonetta

    2015-10-01

    In the setting of acute pulmonary embolism (PE), pulmonary infarction is deemed to occur primarily in individuals with compromised cardiac function.The current study was undertaken to establish the prevalence of pulmonary infarction in patients with acute PE, and the relationship between infarction and: age, body height, body mass index (BMI), smoking habits, clot burden, and comorbidities.The authors studied prospectively 335 patients with acute PE diagnosed by computed tomographic angiography (CT) in 18 hospitals throughout central Italy. The diagnosis of pulmonary infarction on CT was based on Hampton and Castleman's criteria (cushion-like or hemispherical consolidation lying along the visceral pleura). Multivariable logistic regression was used to model the relationship between covariates and the probability of pulmonary infarction.The prevalence of pulmonary infarction was 31%. Patients with infarction were significantly younger and with significantly lower prevalence of cardiovascular disease than those without (P < 0.001). The frequency of infarction increased linearly with increasing height, and decreased with increasing BMI. In logistic regression, the covariates significantly associated with the probability of infarction were age, body height, BMI, and current smoking. The risk of infarction grew with age, peaked at approximately age 40, and decreased afterwards. Increasing body height and current smoking were significant amplifiers of the risk of infarction, whereas increasing BMI appeared to confer some protection.Our data indicate that pulmonary infarction occurs in nearly one-third of the patients with acute PE. Those with infarction are often young and otherwise healthy. Increasing body height and active smoking are predisposing risk factors. PMID:26469892

  13. Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count

    PubMed Central

    Skogmar, Sten; Schön, Thomas; Balcha, Taye Tolera; Sturegård, Erik; Jansson, Marianne; Björkman, Per

    2015-01-01

    Background While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression. Methods Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Results Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Conclusion Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB. PMID:26630153

  14. 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.

  15. 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

  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. Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    2014-01-01

    Background During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Methods Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. Results The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134–353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030). Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). Conclusions COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. PMID:24885188

  18. The Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial II (REACT II): rationale and study design for a clinical trial of physical activity among individuals with chronic obstructive pulmonary disease.

    PubMed

    Foy, Capri G; Wickley, Katie L; Adair, Norman; Lang, Wei; Miller, Michael E; Rejeski, W Jack; Woodard, C Mark; Berry, Michael J

    2006-04-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality in the United States. In addition, persons with COPD are at risk for lower levels of physical activity, leading to further morbidity and mortality. Several studies have demonstrated that long-term exercise therapy confers benefits upon physical functioning among patients with COPD, and some studies indicate that embedding cognitive-behavioral interventions into group-mediated exercise programs is useful in promoting compliance to activity recommendations. However, compliance to long-term activity is low among COPD patients, and the effectiveness of behavioral interventions to enhance long-term activity among these patients has not been extensively explored. Thus, the primary objective of the Reconditioning Exercise and COPD Trial II (REACT II) trial is to determine whether a group-mediated cognitive-behavioral intervention will result in increased physical activity after 12 months, compared to a standard exercise therapy experience among older adults with COPD. The cognitive-behavioral intervention is designed to promote independent physical activity by encouraging participants to self-regulate physical activity with minimal dependence upon staff. The primary study outcome is kcal expended per week in moderate physical activity, and the study is designed to provide 90% power to detect a 400 kcal/week difference in moderate energy expenditure between the two intervention groups. Other outcomes to be compared between the two interventions include physical function, self-reported physical disability, health-related quality of life, exercise capacity, body composition and inflammatory mediators. PMID:16458075

  19. 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.

  20. A functional variant of elafin with improved anti-inflammatory activity for pulmonary inflammation.

    PubMed

    Small, Donna M; Zani, Marie-Louise; Quinn, Derek J; Dallet-Choisy, Sandrine; Glasgow, Arlene M A; O'Kane, Cecilia; McAuley, Danny F; McNally, Paul; Weldon, Sinéad; Moreau, Thierry; Taggart, Clifford C

    2015-01-01

    Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden. PMID:25189740

  1. Muscarinic Receptor Activation Affects Pulmonary Artery Contractility in Sheep: The Impact of Maturation and Chronic Hypoxia on Endothelium-Dependent and Endothelium-Independent Function.

    PubMed

    Giang, Michael; Papamatheakis, Demosthenes G; Nguyen, Dan; Paez, Ricardo; Blum Johnston, Carla; Kim, Joon; Brunnell, Alexander; Blood, Quintin; Goyal, Ravi; Longo, Lawrence D; Wilson, Sean M

    2016-06-01

    Giang, Michael, Demosthenes G. Papamatheakis, Dan Nguyen, Ricardo Paez, Carla Blum Johnston, Joon Kim, Alexander Brunnell, Quintin Blood, Ravi Goyal, Lawrence D. Longo, and Sean M. Wilson. Muscarinic receptor activation affects pulmonary artery contractility in sheep: the impact of maturation and chronic hypoxia on endothelium-dependent and endothelium-independent function. High Alt Med Biol. 17:122-132, 2015.-Muscarinic receptor activation in the pulmonary vasculature can cause endothelium-dependent vasodilation and smooth muscle-dependent vasoconstriction. Chronic hypoxia (CH) can modify both of these responses. This study aimed to assess the combined influence of CH and maturation on endothelium-dependent and endothelium-independent muscarinic-induced vasoreactivity. This was accomplished by performing wire myography on endothelium-intact or endothelium-disrupted pulmonary arterial rings isolated from normoxic or CH fetal and adult sheep. In endothelium-intact arteries, vasodilation was evaluated using cumulative bradykinin doses in phenylephrine and carbachol precontracted pulmonary arterial segments; and vasoconstriction was examined using cumulative doses of carbachol following bradykinin predilation. Effects of nonselective (atropine) and selective M1 (pirenzepine), M2 (AFDX116), and M3 (4-DAMP and Dau5884) muscarinic receptor antagonists were assessed in disrupted arteries. In normoxic arteries, bradykinin relaxation was twofold greater in the adult compared to fetus, while carbachol contraction was fourfold greater. In adult arteries, CH increased bradykinin relaxation and carbachol contraction. In vessels with intact endothelium, maturation and CH augmented maximal response and efficacy for carbachol constriction and bradykinin relaxation. Approximately 50%-80% of adult normoxic and CH endothelium-disrupted arteries contracted to acetylcholine, while ∼50% of fetal normoxic and ∼10% of CH arteries responded. Atropine reduced carbachol

  2. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  3. 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

  4. 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

  5. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    SciTech Connect

    Migliaccio, Christopher T. . E-mail: christopher.migliaccio@umontana.edu; Hamilton, Raymond F.; Holian, Andrij

    2005-06-01

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO{sub 2}). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis.

  6. Carbon Nanotube-Induced Pulmonary Granulomatous Disease: Twist1 and Alveolar Macrophage M1 Activation

    PubMed Central

    Barna, Barbara P.; Huizar, Isham; Malur, Anagha; McPeek, Matthew; Marshall, Irene; Jacob, Mark; Dobbs, Larry; Kavuru, Mani S.; Thomassen, Mary Jane

    2013-01-01

    Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation. To address this hypothesis, wild-type and macrophage-specific peroxisome proliferator-activated receptor gamma (PPARγ) knock out mice were given oropharyngeal instillation of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or PPARγ knock out alveolar macrophages compared to sham controls. Overall, Twist1 expression levels in PPARγ knock out mice were higher than those of wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy controls validated gene array data: qPCR and protein analysis showed significantly elevated Twist1 in sarcoidosis compared to healthy controls. In vitro studies of alveolar macrophages from healthy controls indicated that Twist1 was inducible by classical (M1) macrophage activation stimuli (LPS, TNFα) but not by IL-4, an inducer of alternative (M2) macrophage activation. Findings suggest that Twist1 represents a PPARγ-sensitive alveolar macrophage M1 biomarker which is induced by inflammatory granulomatous disease in the MWCNT model and in human sarcoidosis. PMID:24322444

  7. 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.