Search

Introduction: Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB), leading to an approximate three-fold higher risk of developing active TB. However, epidemiological studies on the prevalence of latent TB infection (LTBI) in DM patients are lacking. In this study, we investigated the presence of LTBI and determined risk factors for LTBI in DM patients. Methodology: We conducted a cross-sectional study at Taipei Medical University-Shuang Ho Hospital in northern Taiwan. The study population comprised DM patients (aged 20-70 years) attending a metabolism outpatient clinic between February 2011 and February 2013, excluding patients who were suspected or confirmed to have active TB. Venous blood samples were drawn from patients to detect LTBI using the QuantiFERON-TB Gold In-Tube (QFT-GIT) method. Results: We enrolled 1120 patients with DM. The QFT-GIT showed positive results for 241 people (21.5%) and negative results for 879 people (78.5%). The mean age at QFT-GIT positivity was 58.2 years, which was significantly dissimilar to the mean age at QFT-GIT negativity, which was 55.0 years (p < 0.001). Multivariate logistic regression indicated that the trend of QFT-GIT positivity increased after the age of 50 years. Effective glycemic control did not differ significantly between QFT-GIT-positive and -negative patients. Moreover, men were predominant were predominant in both QFT-GIT-positive and -negative patients. Conclusions: More than one-fifth of DM patients have LTBI. Among the DM patients, those older than 50 years may have a higher risk of LTBI. Moreover, effective glycemic control did not differ significantly in patients with LTBI.

Epidemiological studies identified the relationship between air pollution and pulmonary tuberculosis. Effects of lung-deposited dose of particulate matter (PM) on culture-positive pulmonary tuberculosis remain unclear. This study investigates the association between lung-deposited dose of PM and pulmonary tuberculosis pleurisy. A case-control study of subjects undergoing pleural effusion drainage of pulmonary tuberculosis (case) and chronic heart failure (control) was conducted. Metals and biomarkers were quantified in the pleural effusion. The air pollution exposure was measured and PM deposition in the head, tracheobronchial, alveolar region, and total lung region was estimated by Multiple-path Particle Dosimetry (MPPD) Model. We performed multiple logistic regression to examine the associations of these factors with the risk of tuberculosis. We observed that 1-μg/m3 increase in PM10 was associated with 1.226-fold increased crude odds ratio (OR) of tuberculosis (95% confidence interval (CI): 1.023-1.469, p

Air pollution has been recognized to be a risk factor for lung cancer. The objective of this study was to investigate the effects of air pollution on heavy metal alterations in the pleural effusion of lung cancer patients. Pleural effusion was collected from patients with lung cancer and congestive heart failure (CHF). One-year average levels of particulate matter with an aerodynamic diameter of < 10 µm (PM10), PM2.5, NO2, and SO2 were linked to the exposure of these subjects. Traffic-related metals, included Al, Fe, Cu, Zn, and Pb, were determined in the pleural effusion. Logistic regression models were used to examine their associations. There were 63 lung cancer patients and 31 CHF patients enrolled in the current study. We found that PM10, PM2.5, and NO2 were negatively correlated with Al in the pleural effusion, whereas PM2.5 was positively correlated with Zn in the pleural effusion. Increases in 1 μg/m3 of PM2.5 and 1 ng/mL of Zn were associated with lung cancer (adjusted OR=2.394, 95% CI= 1.446-3.964 for PM2.5; adjusted OR=1.003, 95% CI=1.000-1.005 for Zn). Increases in PM2.5 and Zn in the pleural effusion increased the risk of malignant pleural effusion in lung cancer patients (adjusted OR=1.517; 95% CI=1.082-2.127 for PM2.5; adjusted OR=1.002, 95% CI=1.000-1.005 for Zn). Furthermore, we observed that adenocarcinomas increased in association with a 1-μg/m3 increase in PM2.5 (crude OR=1.683; 95% CI=1.006-2.817) in lung cancer patients. In conclusion, PM2.5 exposure and the possible resultant Zn in the pleural effusion associated with the development of malignant pleural effusion in lung cancer.

Air pollution has been recognized to be a risk factor for lung cancer. The objective of this study was to investigate the effects of air pollution on heavy metal alterations in the pleural effusion of lung cancer patients. Pleural effusion was collected from patients with lung cancer and congestive heart failure (CHF). One-year average levels of particulate matter with an aerodynamic diameter of 10 µm (PM

// Po-Hao Feng 1, 2 , Chih-Teng Yu 3 , Kuan-Yuan Chen 1, 4 , Ching-Shan Luo 1 , Shen Ming Wu 1 , Chien-Ying Liu 3 , Lu Wei Kuo 1 , Yao-Fei Chan 3 , Tzu-Tao Chen 1 , Chih-Cheng Chang 1 , Chun-Nin Lee 1 , Hsiao-Chi Chuang 5 , Chiou-Feng Lin 6 , Chia-Li Han 7 , Wei-Hwa Lee 8 and Kang-Yun Lee 1, 2 1 Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan 2 Division of Thoracic Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 Division of Pulmonary Medicine, Department of Internal Medicine, Chang Gung Medical Foundation Linko Branch, Taoyuan, Taiwan 4 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 7 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan 8 Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan Correspondence to: Kang-Yun Lee, email: lee4949@ms41.hinet.net Keywords: lung cancer; myeloid derived suppressor cells; epidermal growth factor receptor; macrophages; NF-kappa B Received: September 06, 2017 Accepted: January 03, 2018 Published: January 10, 2018 ABSTRACT Background: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Results: Blood monocytic S100A9 + MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9 + MDSCs in PBMC were well correlated to tumor infiltrating CD68 + and S100A9 + cells, suggesting an origin of TAMs. Patient’s MDMs, mostly from S100A9 + MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the RELB signaling genes, confirmed by Western blotting and functionally by RELB knockdown. Conclusions: In conclusion, blood S100A9 + MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB RELB pathway. Methods: Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.

A molecular imaging probe comprising superparamagnetic iron oxide (SPIO) nanoparticles and Mycobacterium tuberculosis surface antibody (MtbsAb) was synthesized to enhance imaging sensitivity for extrapulmonary tuberculosis (ETB). An SPIO nanoprobe was synthesized and conjugated with MtbsAb. The purified SPIO-MtbsAb nanoprobe was characterized using TEM and NMR. To determine the targeting ability of the probe, SPIO-MtbsAb nanoprobes were incubated with Mtb for in vitro imaging assays and injected into Mtb-inoculated mice for in vivo investigation with magnetic resonance (MR). The contrast enhancement reduction on magnetic resonance imaging (MRI) of Mtb and THP1 cells showed proportional to the SPIO-MtbsAb nanoprobe concentration. After 30 min of intravenous SPIO-MtbsAb nanoprobe injection into Mtb-infected mice, the signal intensity of the granulomatous site was enhanced by 14-fold in the T2-weighted MR images compared with that in mice receiving PBS injection. The MtbsAb nanoprobes can be used as a novel modality for ETB detection.

Background The study compared the predictive outcomes of artificial neural network, support vector machine and random forest on the occurrence of anti-tuberculosis drug-induced hepatotoxicity. Methods The clinical and genomic data of patients treated with anti-tuberculosis drugs at Taipei Medical University-Wanfang Hospital were used as training sets, and those at Taipei Medical University-Shuang Ho Hospital served as test sets. Features were selected through a univariate risk factor analysis and literature evaluation. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve were calculated to compare the traditional, genomic, and combined models of the three techniques. Results Nine models were created with 7 clinical factors and 4 genotypes. Artificial neural network with clinical and genomic factors exhibited the best performance, with an accuracy of 88.67%, a sensitivity of 80%, and a specificity of 90.4% for the test set. The area under the receiver operating characteristic curve of this best model reached 0.894 for training set and 0.898 for test set, which was significantly better than 0.801 for training set and 0.728 for test set by support vector machine and 0.724 for training set and 0.718 for test set by random forest. Conclusions Artificial neural network with clinical and genomic data can become a clinical useful tool in predicting anti-tuberculosis drug-induced hepatotoxicity. The machine learning technique can be an innovation to predict and prevent adverse drug reaction.

Epidemiological evidence has shown that air pollution is associated with chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate the effects of air pollution on patients with COPD and pneumonia. A case-control study of patients who had undergone thoracentesis for pleural effusion drainage in a hospital was recruited for this study. COPD and non-COPD patients with pneumonia respectively served as the case and control groups. Increases in particulate matter of2.5 μm in aerodynamic diameter (PM

In vitro models have demonstrated immune-modulating effects of bevacizumab (BEV). Combinations of an EGFR tyrosine kinase inhibitor (TKI) with BEV improve progression-free survival (PFS) in patients with EGFR-mutated lung adenocarcinoma. How BEV confers this clinical effect and the underlying mechanisms of its effect are not clear.A total of 55 patients with stage 4 EGFR-mutated lung adenocarcinoma were enrolled. Myeloid-derived suppressor cells (MDSCs), type 1 and type 2 helper T cells, and cytotoxic T lymphocytes were analyzed by flow cytometry. Clinical data were collected for analysis.In all, 25 patients received EGFR TKI and BEV combination therapy (the BEV/TKI group) and 30 patients received EGFR TKI monotherapy (the TKI-only group). The BEV/TKI group had longer PFS (23.0 versus 8.6 months [p = 0.001]) and, in particular, better intracranial control rates (80.0% versus 43.0% [p = 0.03]), a longer time to intracranial progression (49.1 versus 12.9 months [p = 0.002]), and fewer new brain metastases (38.0% versus 71.0% [p = 0.03]) than the TKI-only group did. The BEV/TKI group had a lower percentage of circulating MDSCs (20.4% ± 6.5% before treatment versus 12.8% ± 6.6% after treatment, respectively [p = 0.02]), and higher percentages of type 1 helper T cells (22.9% ± 15.3% versus 33.2% ± 15.6% [p0.01]) and cytotoxic T lymphocytes (15.5% ± 7.2% versus 21.2% ± 5.6% [p0.01]) after treatment, changes that were not seen in the TKI-only group. Pretreatment percentage of MDSCs was correlated with PFS, with this correlation attenuated after BEV/TKI treatment. Percentage of MDSCs was also associated with shorter time to intracranial progression.Combining a EGFR TKI with BEV extended PFS and protected against brain metastasis. Those effects were probably due to the reduction of circulating S100A9-positive MDSCs by BEV, which leads to restoration of effective antitumor immunity. Our data also support the rationale for a BEV-immune checkpoint inhibitor combination.

Twenty-five to 40% of patients pass a spontaneous breathing trial (SBT) but fail to wean from mechanical ventilation. There is no single appropriate and convenient predictor or method that can help clinicians to accurately predict weaning outcomes. This study designed an artificial neural network (ANN) model for predicting successful extubation in mechanically ventilated patients.Ready-to-wean subjects (N = 121) hospitalized in medical ICUs were recruited and randomly divided into training (n = 76) and test (n = 45) sets. Eight variables consisting of age, reasons for intubation, duration of mechanical ventilation, Acute Physiology and Chronic Health Evaluation II score, mean inspiratory and expiratory times, mean breathing frequency, and mean expiratory tidal volume in a 30-min SBT (pressure support ventilation of 5 cm H2O and PEEP of 5 cm H2O) were selected as the ANN input variables. The prediction performance of the ANN model was compared with the rapid shallow breathing index (RSBI), maximum inspiratory pressure, RSBI at 1 min (RSBI1) and 30 min (RSBI30) in an SBT, and absolute percentage change in RSBI from 1 to 30 min in an SBT (ΔRSBI30) using a confusion matrix and receiver operating characteristic curves.The area under the receiver operating characteristic curves in the test set of the ANN model was 0.83 (95% CI 0.69-0.92, P.001), which is better than any one of the following predictors: 0.66 (95% CI 0.50-0.80, P = .04) for RSBI, 0.52 (95% CI 0.37-0.67, P = .86) for maximum inspiratory pressure, 0.53 (95% CI 0.37-0.68, P = .79) for RSBI1, 0.60 (95% CI 0.44-0.74, P = .34) for RSBI30, and 0.51 (95% CI 0.36-0.66, P = .91) for ΔRSBI30. Predicting successful extubation based on the ANN model of the test set had a sensitivity of 82%, a specificity of 73%, and an accuracy rate of 80%, with an optimal threshold of ≥ 0.5 selected from the training set.The ANN model improved the accuracy of predicting successful extubation. By applying it clinically, clinicians can select the earliest appropriate weaning time.

Erlotinib (Tarceva) is an oral epidermal growth factor receptor-tyrosine kinase inhibitor that is mainly used for patients with advanced or metastatic non-small-cell lung cancer. Tyrosine kinase signaling cascades also play a critical role in the pathogenesis of allergic airway inflammation and airway remodeling. However, cholinergic effects caused by erlotinib on tracheal smooth muscle remain unclear. The objective of this study was to determine the effects of erlotinib on the isolated rat tracheal smooth muscle in vitro . To examine the cholinergic effects of erlotinib, in vitro rat tracheal smooth muscle was used to assess alterations in methacholine-induced contraction (served as a parasympathetic mimetic) and electrically induced contraction. The results demonstrated that the addition of erlotinib (from 1 × 10 −8 M to 1 × 10 −4 M) induced no significant effects on tracheal tension after methacholine treatment. Furthermore, erlotinib did not affect electrical field stimulation-induced spike contraction. This study demonstrated that erlotinib had no cholinergic effects in vitro , suggesting it may be safe for asthmatic patients with non-small-cell lung cancer after further investigation.

Background. Cisplatin and carboplatin cause nephrotoxicity by forming platinum-DNA adducts and lead to cell death.Methods. One-hundred and sixteen Taiwanese lung cancer patients who received cisplatin or carboplatin more than twice were recruited, and their genotypes were determined. The risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease (RIFLE) criteria were used to evaluate the occurrence of nephrotoxicity. A logistic regression, multiple regression with a classification and regression tree (CART), and the Framingham study risk score were used to analyze interactions between genetic and nongenetic factors in producing platinum-induced nephrotoxicity.Results.ERCC1118C andTP5372Arg polymorphisms were associated with increased risks of platinum-induced nephrotoxicity. Other risk factors found included the platinum type, baseline serum creatinine (Scr), coadministration of vinorelbine, and the number of chemotherapy cycles. The overall prediction rate of the CART was 82.7%, with a sensitivity of 0.630 and specificity of 0.896. The Framingham study risk prediction model contained 7 factors. Its prediction rate was 84.5%, with a sensitivity of 0.643 and specificity of 0.909.Conclusions. Genetic polymorphisms ofERCC1andTP53are risk factors for nephrotoxicity. The CART analysis may provide a clinically applicable model to predict the risk of cisplatin- and carboplatin-induced nephrotoxicity.

Considerable evidence shows a key role for protein modification in the adverse effects of chemicals; however, the interaction of diesel exhaust particles (DEP) with proteins and the resulting biological activity remains unclear. DEP and carbon black (CB) suspensions with and without bovine serum albumin (BSA) were used to elucidate the biological effects of air pollutants. The DEP and CB samples were then divided into suspensions and supernatants. Two important goals of the interaction of DEP with BSA were as follows: (1) understanding BSA modification by particles and (2) investigating the effects of particles bound with BSA and the corresponding supernatants on cellular oxidative stress and inflammation. We observed significant free amino groups production was caused by DEP. Using liquid chromatography–mass spectrometry (LC−MS), we observed that BSA was significantly oxidised by DEP in the supernatants and that the peptides ETYGDMADCCEK, MPCTEDYLSLILNR and TVMENFVAFVDK, derived BSA-DEP conjugates, were also oxidised. In A549 cells, DEP-BSA suspensions and the corresponding supernatants reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) production and increased interleukin-6 (IL-6) levels when compared to DEP solutions without BSA. Our findings suggest that oxidatively modified forms of BSA caused by DEP could lead to oxidative stress and the activation of inflammation.

Kuan-Yuan Chen,1,2 Po-Hao Feng,1,2 Chih-Cheng Chang,1 Tzu-Tao Chen,1 Hsiao-Chi Chuang,1,3 Chun-Nin Lee,1,3 Chien-Ling Su,1,3 Lian-Yu Lin,4 Kang-Yun Lee,1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, 2Department of Internal Medicine, School of Medicine, 3School of Respiratory Therapy, College of Medicine, Taipei Medical University, 4Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China Abstract: Lymphocytic pleurisy is commonly observed in tuberculosis and cancer. Noninvasive biomarkers are needed to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE) because current clinical diagnostic procedures are often invasive. We identified immune response biomarkers that can discriminate between TPE and MPE. Fourteen pleural effusion biomarkers were compared in 22 MPE patients and five TPE patients. Of the innate immunity biomarkers, the median levels of interleukin (IL)-1β and interferon-induced protein-10 (IP-10) were higher in TPE patients than in MPE patients (P

Particulate matter (PM) modulates the expression of autophagy; however, the role of selective autophagy by PM remains unclear. The objective of this study was to determine the underlying mechanisms in protein oxidation and degradation caused by PM. Human epithelial A549 cells were exposed to diesel exhaust particles (DEPs), urban dust (UD) and carbon black (CB; control particles). Cell survival and proliferation were significantly reduced by DEPs and UD in A549 cells. First, benzo(a)pyrene diolepoxide (BPDE) protein adduct was caused by DEPs at 150 μg/ml. Methionine oxidation (MetO) of human albumin proteins was induced by DEPs, UD and CB; however, the protein repair mechanism that converts MetO back to methionine by methionine sulfoxide reductases A (MSRA) and B3 (MSRB3) was activated by DEPs and inhibited by UD, suggesting that oxidized protein was accumulating in cells. As to the degradation of oxidized proteins, proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation. The results suggest that CB-induced protein degradation may be via an ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation may be via an ubiquitin-independent autophagy pathway. A distinct proteotoxic effect may depend on the physicochemistry of PM.

Background For patients with bronchiectasis, the mechanical mobilization of secretion constitutes a key therapeutic approach. However, the effectiveness of lung expansion therapy to mobilize secretion in bronchiectasis patients has not been investigated extensively. This study compares patients' exercise tolerance and physical assessment outcomes after secretion clearance using intermittent positive pressure breathing (IPPB) or negative pressure ventilation (NPV) as adjuncts to postural drainage. Methods This prospective, randomized crossover study examined the data for 18 stable outpatients with bronchiectasis. The outcomes were compared for four treatment sessions of either IPPB or NPV, used as adjuncts to postural drainage. The short-term outcomes involved pulmonary functions and a six-minute walk test (6MWT). We also assessed pulmonary functions and physical clinical signs as immediate treatment effects. Results Patients' forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and cough efficacy did not change significantly after individual postural drainage sessions using either IPPB or NPV. However, a reduction in the use of accessory muscles was noted after NPV; patients with low baseline FVC might benefit particularly from this reduction (r = 0.699, p

Background Dyspnea and related disabling symptoms are common in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnia. Unfortunately, the indicators during the six-minute walk test (6MWT) for prediction of respiratory functions or exercise intolerance in severe COPD has been little investigated. The relationship between parameters during the 6MWT and respiratory functions was therefore assessed in COPD patients with chronic hypercapnia. Methods In 2002 and 2003, 37 COPD outpatients with chronic hypercapnia performed the 6MWT, and their respiratory function was measured. Twenty-eight males and nine females with COPD (mean forced expiratory volume in the first second of 26.1% of the predicted value, SD 7.7%) and hypercapnia (mean PaCO2 of 55.5 mmHg, SD 6.4 mmHg) were recruited. All patients were tested to measure pulmonary function, respiratory drive (airway occlusion pressure at 100 ms, P0.1), and respiratory muscle strength on the first day. On the second day, arterial blood gas analysis and the 6MWT were performed. Pearson’s correlation coefficient and regression analysis were used for data analysis. Results The study showed that the six-minute walk distance (6MWD) was weakly correlated with the resting arterial oxygen partial pressure (PaO2) (r = 0.349, p = 0.034), expiratory muscle strength (Pemax) (r = 0.358, p = 0.030), and changes of dyspnea sensation (∆Borg) (r = 0.385, p = 0.019); furthermore, ∆Borg was weakly correlated with Pemax (r = 0.377, p = 0.021). The oxygen saturation measured at the end of the 6MWT (ExSpO2) was significantly correlated with FEV1/FVC (r = −0.443, p = 0.006), pH (r = 0.375, p = 0.022), arterial carbon dioxide partial pressure (PaCO2) (r = −0.470, p = 0.003), PaO2 (r = 0.664, p = 0.000) and P0.1 (r = −0.344, p = 0.037). The results of the multiple linear regression with the 6MWD as the dependent variable revealed that PaO2, Pemax, and ∆Borg were significant determinants of the 6MWD (p = 0.018, adjusted R2 = 0.259). Conclusion Measurement of the 6MWT demonstrated that a stronger association of exercise limitation is the value of ∆Borg in COPD patients with chronic hypercapnia. Ventilation constraints, hypoxemia, hypercapnia, and respiratory drive might be associated with oxygen desaturation during the 6MWT in COPD patients with chronic hypercapnia.

SummaryObjectiveThe aim of this study was to evaluate the reversible factors that could possibly affect outcomes of anti-tuberculosis (anti-TB) treatment.MethodsA retrospective observational nested case–control study was performed to evaluate the association of patient and clinical factors with anti-TB therapy outcomes as defined by the World Health Organization (WHO).ResultsTo examine the impact of a variety of factors on the outcomes of anti-TB treatment, a total of 302 TB patients were included in the study. Univariate analysis revealed that age, gender, concurrent hypertension, asthma/chronic obstructive pulmonary disease, or liver disease, worsened baseline blood urea nitrogen or creatinine, ethambutol 20 cigarettes per day) was significantly associated with a decreased odds of cure or treatment completion (odds ratio 0.23, 95% confidence interval 0.05–0.98, p=0.047).ConclusionsAs smoking significantly inhibits the effectiveness of TB treatment, the integration of smoking cessation into TB treatment programs is strongly advocated to reduce the dual global burden of smoking and TB.

Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated.Blood monocytic S100A9In conclusion, blood S100A9Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.

Objective: The objective of this study was to evaluate the impact of an asthma continuing education program on pharmacists’ knowledge and attitudes related to asthma pharmaceutical care. Subjects and Methods: A 20-hour continuing education program was conducted by the joint efforts of the Taipei City Government, Taiwan Association of Asthma Education and Taipei Medical University Wan Fang Hospital, in a series of 4 days afternoon sessions from June 26 to July 4, 2004. One hundred and twenty-five pharmacists participated. The Asthma Knowledge Test in Mandarin and the Asthma Attitude Scale in Mandarin were developed by adapting the scale used to evaluate the impact of pharmacist continuing education programs on diabetic care. The results before and after the intervention were compared to evaluate the impact of the program. Results: Of the 125 participants, 105 returned both the pre- and post-intervention questionnaires, for a response rate of 84.0%. The total score of the attitude section increased significantly from 40.04 ± 3.35 to 42.54 ± 2.98 (full score = 50, p < 0.001). The total score of the knowledge section also increased significantly from 7.18 ± 1.31 to 7.56 ± 1.15 (p = 0.008). Improvement in the attitude score was found in 70 (67.0%) subjects, and in the knowledge score in 45 (43.5%) subjects. Conclusion: The study demonstrated that attitude and knowledge toward asthma care improved after the continuing education program. Further study of long-term impact and direct changes in asthma pharmaceutical care practice will be necessary.

Kuan-Yuan Chen,1,* Kai-Jen Chuang,2,3,* Hui-Chiao Liu,4,5 Kang-Yun Lee,1,6 Po-Hao Feng,1,6 Chien-Ling Su,1,4 Chii-Lan Lin,1,4 Chun-Nin Lee,1,4 Hsiao-Chi Chuang1,4 1Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, 2Department of Public Health, School of Medicine, College of Medicine, 3School of Public Health, College of Public Health and Nutrition, 4School of Respiratory Therapy, College of Medicine, Taipei Medical University, 5Division of Pulmonary Medicine, Department of Internal Medicine, Sijhih Cathay General Hospital, 6Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan *These authors contributed equally tothe study Abstract: Emerging risk factors for tuberculosis (TB) infection, such as air pollution, play a significant role at both the individual and population levels. However, the association between air pollution and TB remains unclear. The objective of this study was to examine the association between outdoor air pollution and sputum culture conversion in TB patients. In the present study, 389 subjects were recruited from a hospital in Taiwan from 2010 to 2012: 144 controls with non-TB-related pulmonary diseases with negative sputum cultures and 245 culture-positive TB subjects. We observed that a 1 µg/m3 increase in particulate matter of ≤10 µm in aerodynamic diameter (PM10) resulted in 4% higher odds of TB (odds ratio =1.04, 95% confidence interval=1.01–1.08, P

BackgroundThe incidence of tuberculosis (TB) has been falling in many developed countries; however, there is a trend of an increasing proportion of TB among the elderly. The aim of this study was to evaluate the age transition of patients with TB in Taiwan from 1957 to 2001.MethodsData on the number of TB cases and patient age were collected from the National Tuberculosis Registry for three different 5-year periods: 1957-1961, 1977-1981, and 1997-2001. The distribution of TB cases in these three different periods was analyzed.ResultsThe age distributions of TB patients were different among the 1957-61 (n = 26,000), 1977-81 (n = 31,363) and 1997-2001 (n = 71,447) groups. During the 1957-61 period, the most common age group was 25-44 years (50.9%). During 1977-81, the most common age group was 45-64 years (44.9%). In 1997-2001, the most common age group had shifted to people aged 65 years or older (43.7%). For the whole period from 1957 to 2001, after adjusting for age shifts in the general population, the proportion of TB patients had significantly increased in persons 65 years or older, slightly increased in persons aged 0-14 years, and decreased in the 15-24, 25-44, and 45-64-year-old age groups. For the period 1977-2001, age-specific registered case rates increased with age.ConclusionThe age of TB patients in Taiwan showed a rising trend from 1957 to 2001. A high index of suspicion and prompt investigation of elderly patients with signs and symptoms characteristic of TB may allow earlier diagnosis and treatment.

Purpose. The compatibility, pH, and osmolality of N -acetylcysteine (NAC) nebulizing solution in the presence of ipratropium bromide or fenoterol hydrobromide were studied. Methods. Portions (400 μL) of each mixture were sampled immediately upon mixing and one, two, three, four, five, six, and seven hours after mixing and assayed by high-performance liquid chromatography. Osmolality was measured by sampling 100 μL from the filling cup at a five-minute interval during nebulization and by the freezing-point-depression method. Results. Adding NAC solution to fenoterol solution raised the pH from 3.20 to 7.90 and the osmolality to a mean ± S.D. of 1400.67 ± 4.51 mOsm/kg. Fenoterol concentrations decreased to 93.71% and NAC concentrations to 92.54% of initial concentrations after seven hours. Mixing ipratropium with NAC solution raised the pH from 3.74 to 7.95 and the osmolality to a mean ± S.D. of 1413 ± 11.79 mOsm/kg. The initial ipratropium concentration declined 7.39% and 10.91% one and two hours after mixing with NAC solution, respectively. Conclusion. NAC and ipratropium were stable in nebulizing solution within one hour of mixing. NAC and fenoterol were compatible for at least seven hours.

Exposure to particulate matter less than 2.5 μm (PM2.5) in size is an urgent issue for the protection of human health. Chemicals with PM2.5 collected during a period of intensive haze episodes in Beijing (BJ), Xian (XA) and Hong Kong (HK) were characterised for organic carbon (OC), elemental carbon (EC), total carbon (TC) and free amino acids. BALB/c mice underwent aspiration exposure of 50 or 150 μg of PM2.5/mouse (BJ, XA and HK) on days 1 and 7 and were euthanised on day 14. The effects of these exposures on E-cadherin and inflammatory responses in the mouse lungs were analysed. The PM2.5 chemicals consisted of significant amounts of OC: 36.6 ± 17.2 μg/m(3) for BJ, 38.8 ± 3.8 μg/m(3) for XA and 7.2 ± 1.4 μg/m(3) for HK. A total of 23 free amino compounds for the PM2.5 samples were analysed: 4075 ± 1578 pmol/m(3) for BJ, 4718 ± 2190 pmol/m(3) for XA and 1145 ± 213 pmol/m(3) for HK. Exposure to PM2.5 resulted in the suppression of E-cadherin levels in the lung tissues and increased IFN-γ, IL-2, IL-4, IL-6 and IL-10 in the bronchoalveolar lavage fluid. The alterations in E-cadherin, IFN-γ, IL-6 and IL-10 were associated with OC, TC and some amino acids, particularly non-protein-type amino acids. These data emphasised the deleterious health effects of PM2.5.

Background and Purpose Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD. This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design. Methods The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort. Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders. Results Of the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001). Treatment with SABA was associated with 1.67-fold (95% CI 1.45–1.91; p < 0.001) increased risk of stroke in COPD patients. By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60–0.94, p = 0.014). Conclusions Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction. Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD.

Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves of Stevia rebaudiana (Compositae). It has been used popularly in Japan and Brazil as a sugar substitute for decades. Previous study has shown that it lowered blood pressure in spontaneously hypertensive rats (SHRs) when administered intravenously. This study shows that intraperitoneal injection of stevioside 25 mg/kg also has antihypertensive effect in SHRs. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel. This phenomenon was further confirmed in cultured aortic smooth muscle cells (A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic rings, showing that this vasorelaxation effect was not related to nitric oxide. The present data show that the vasorelexation effect of stevioside was mediated mainly through Ca(2+) influx inhibition.

In order to evaluate the incidence, predisposing factors and clinical course of antituberculous drug-induced liver injury in hepatitis B surface antigen (HBsAg)-positive carriers and non-carriers, in an area endemic for hepatitis B, we prospectively followed 240 patients (154 male, 86 female; mean age 40 years) who had received daily isoniazid, rifampicin, ethambutol and pyrazinamide for the treatment of pulmonary tuberculosis. Patients with heavy alcohol consumption, with pretreatment serum alanine aminotransferase (ALT) elevation and who had less than 3 months post-treatment follow-up were excluded from the study. Thirty-one (13%) patients were positive for serum HBsAg before treatment. Sixty-three (26%; 95% CI: 21-32%) patients developed antituberculous drug-induced liver injury. The incidence of drug-induced liver injury was significantly more frequent in patients35 years of age than in patientsor = 35 years of age (33 vs 17%; P0.05), but was not different between HBsAg carriers and non-carriers (29 vs 26%; P0.05). Using step-wise logistic regression analysis, patient age35 years was the only independent variable for predicting antituberculous drug-induced liver injury, while sex, acetylator phenotype, HBsAg carrier status and severity of tuberculosis were not. The peak serum ALT levels in antituberculous drug-induced liver injury were not significantly different between HBsAg carriers and non-carriers. Only one 61-year-old HBsAg carrier developed severe jaundice after 6 months antituberculous therapy; he subsequently died of hepatic failure. In conclusion, the incidence of antituberculous drug-induced liver injury was significantly higher in patients35 years of age than in patientsor = 35 years of age, but was not different between HBsAg carriers and non-carriers. Mortality occurred in an aged HBsAg carrier superimposed with antituberculous drug-induced liver injury.

A considerable amount of studies have been conducted to investigate the interactions of biological fluids with nanoparticle surfaces, which exhibit a high affinity for proteins and particles. However, the mechanisms underlying these interactions have not been elucidated, particularly as they relate to human health. Using bovine serum albumin (BSA) and mice bronchoalveolar lavage fluid (BALF) as models for protein–particle conjugates, we characterized the physicochemical modifications of carbon blacks (CB) with 23 nm or 65 nm in diameter after protein treatment. Adsorbed BALF-containing proteins were quantified and identified by pathways, biological analyses and protein classification. Significant modifications of the physicochemistry of CB were induced by the addition of BSA. Enzyme modulators and hydrolase predominately interacted with CB, with protein-to-CB interactions that were associated with the coagulation pathways. Additionally, our results revealed that an acute-phase response could be activated by these proteins. With regard to human health, the present study revealed that the CB can react with proteins (∼55 kDa and 70 kDa) after inhalation and may modify the functional structures of lung proteins, leading to the activation of acute-inflammatory responses in the lungs.

Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed between 1988 and 1990 were treated with isoniazid and at least three other effective second-line drugs based on in vitro susceptibility tests. Of these patients, 10% failed to adhere to the regimen and 43% remained sputum positive after 6 months of treatment. Only 47% showed sputum conversion within 6 months of treatment and 12% of them relapsed during the first year of follow-up. From September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen containing rifabutin, isoniazid and at least three other susceptible drugs. Only 47% achieved a sustained sputum conversion. Four died during treatment due to disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed to adhere to the regimen for more than 1 month during the first 6 months of therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73% achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months. No significant adverse effect was associated with ofloxacin use. We concluded that ofloxacin is a better choice among the more toxic and less potent second-line drugs, and should be used along with other anti-TB drugs in treating patients with MDR-TB.

Mannose-binding lectin (MBL) deficiency is associated with susceptibility to respiratory infections. We investigated the impact of MBL2 gene polymorphisms and MBL deficiency on the recurrence of infective exacerbation in patients with COPD.A prospective study was conducted among 215 patients with COPD and 137 healthy subjects. MBL deficiency was determined by the MBL2 gene polymorphisms and serum levels of MBL.The average frequency of infective exacerbations over 3 years in the 215 patients with COPD was 2.5 ± 1.3 episodes. The COPD group with three or more episodes of infective exacerbation (recurrent exacerbators) included 96 patients, and the remaining 119 patients had two or fewer episodes (less-frequent exacerbators). Among the 96 recurrent exacerbators, 12 (12.50%) had the MBL deficiency genotype compared with 5 (4.20%) among the less-frequent exacerbators (OR, 3.25; 95% CI, 1.01-11.07; P = .0253). In recurrent exacerbators, the frequency of infective exacerbation was significantly higher in patients with MBL-deficient genotypes than in those with non-MBL-deficient genotypes (4.75 ± 1.22 vs 3.52 ± 0.78, respectively; P.0001). In addition, mortality was significantly increased in recurrent exacerbators with MBL-deficient genotypes compared with those with non-MBL-deficient genotypes (66.7% vs 31.0%, respectively; P = .0153).MBL deficiency due to MBL2 polymorphisms increases the risk of recurrent infective exacerbation and worsens its outcome in patients with COPD.

Massive hemoptysis is described in many disease processes. However, a mediastinal teratoma is rarely considered in a patient presenting with massive hemoptysis. Since a mediastinal teratoma has no specific symptoms, its definitive diagnosis is difficult before surgical intervention. Flexible bronchoscopy can be diagnostic in cases of a mediastinal teratoma with involvement of the bronchial tree. We report 2 cases of hemoptysis caused by mediastinal teratoma with bronchial communication.

Hepatocelluar carcinoma (HCC) is the most lethal cancer in the world. Most HCC over-express c-Myc, which plays a critical role in regulating cellular growth, differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers. Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma. Here, we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF. We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach. Although this strategy is currently not available in clinics, with recent advances in better drug design, pharmacokinetics and pharmacogenetics, inhibition of c-Myc might become a novel therapy for HCC in the future.

Identifying the risk factors responsible for lung cancer especially for nonsmokers is critical for both its prevention and treatment. Studies have linked the polymorphisms in N -acetyltransferases (NAT2), a key enzyme for metabolism of hydrocarbons, with lung cancer in Asian female nonsmokers. Since a high percentage of lung adenocarcinoma in Asian female nonsmokers contains activating hotspot mutations in epidermal growth factor receptors (EGFR), we hypothesized that NAT2 polymorphisms might represent a risk factor in lung cancer with EGFR mutations. We studied NAT polymorphisms in 117 nonsmall cell lung cancer (NSCLC) patients and in 119 healthy controls and EGFR hotspot mutations in exons 18–21 in 100 of the 117 patients using polymerase chain reactions. NAT2 fast acetylator genotypes were significantly associated with patients with lung cancer ( P =0.04, odds ratio (OR): 1.90, 95% confidence interval (CI): 1.02–3.57). Further analyses revealed that NAT2 fast acetylator genotypes were significantly associated with NSCLC with wildtype EGFR ( P =0.008, OR: 3.16, 95% CI: 1.31–7.63), but not with those with EGFR mutations ( P =0.40). Therefore, NAT2 fast acetylator genotypes are a potential risk factor especially for lung cancer with wildtype EGFR.

Objective 2-Methoxyestradiol (2ME2) has been shown to induce apoptosis in leukemic cells, but its exact mechanism remains unclear. Because c-Myc plays a critical role in leukemogenesis, we evaluated whether 2ME2 acts on acute myeloid leukemia (AML) through modulation of c-Myc activity. Materials and Methods AML cell lines and primary AML leukemia were treated with 2ME2 and the relationship between 2ME2-induced apoptosis and changes in c-Myc activity was examined. Results 2ME2 induced mitochondrial apoptosis of human AML cells through increased reactive oxygen species. Further investigation showed that 2ME2 downregulated c-Myc expression in a time-dependent manner. Increased oxidative stress led to downregulation of c-Myc mRNA and protein, but did not affect the stability of c-Myc protein. To demonstrate the role of c-Myc in 2ME2-induced apoptosis, we ectopically expressed wild-type c-Myc in AML cells and found that ectopic expression of c-Myc abrogated the 2ME2-induced apoptosis. In addition, we showed that 2ME2 treatment inhibited phosphorylation of Akt and binding of nuclear factor-κB p65/p50 heterodimers to its DNA targets. As with results from cell lines studied, 2ME2 also induced cytotoxicity to primary AML cells and downregulated their c-Myc expression and induced apoptosis. Conclusion Downregulation of c-Myc is critical for 2ME2-induced oxidative stress and apoptosis in AML cells. Our results might be extended to other types of cancers overexpressing c-Myc.

Hsiao-Chi Chuang,1,2,* Chien-Ling Su,1,2,* Hui-Chiao Liu,2 Po-Hao Feng,1,3 Kang-Yun Lee,1,3 Kai-Jen Chuang,4,5 Chun-Nin Lee,1,2 Mauo-Ying Bien2,6 1Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, 2School of Respiratory Therapy, 3Department of Internal Medicine, 4Department of Public Health, School of Medicine, College of Medicine, 5School of Public Health, College of Public Health and Nutrition, 6Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan *These authors contributed equally tothis work Objective: Smoking has been associated with tuberculosis (TB); however, the effects of smoking on the effectiveness of TB treatment remain unclear.Materials and methods: Data were retrieved from case notes and interviews of subjects registered in the TB-reporting system from 2010 to 2012. Study cases were defined as subjects with TB-positive sputum cultures, whereas the controls were defined as subjects with non-TB-related pulmonary diseases. Statistical analyses included logistic regression and multivariate Cox proportional hazard regression models.Results: A total of 245 cases with cultures positive for TB and 114 controls with non-TB-related pulmonary diseases and negative sputum cultures were recruited. Current smokers had the highest failure rate (33%) for TB treatment, and they had the most severe pulmonary lesions based on chest X-ray grading. Current smokers had a 1.36-fold (95% confidence interval 1.03–2.36, P

People living in aboriginal areas of Taiwan are known to be at especially high risk of developing tuberculosis (TB). This study investigated the incidence and mortality of TB in aboriginal areas of Taiwan.The TB death statistics and notification data from the National TB Register and Department of Health in 1997-2001 were analyzed.From 1997 to 2001, people living in aboriginal areas bore a disproportionate burden of TB disease in Taiwan, with mortality rates 5.5-6.5 times and incidence rates 3.6-5.2 times higher than those of people living in non-aboriginal areas. Among patients with TB living in aboriginal areas, 381 died, accounting for 5.1% of the 7480 TB deaths in Taiwan. A large proportion of the patients with TB who died were older than 65 years, in both aboriginal (40.2%) and non-aboriginal (78.5%) areas; however, the age of TB patients who died in non-aboriginal areas was significantly older (p0.001). TB patients living in the aboriginal areas accounted for 3.6% (2618/71,447) of the total number of reported TB patients in Taiwan, and 32.7% were in the age range from 24-45 years. In contrast, TB patients living in non-aboriginal areas were typically older, with only 20.1% in the 24-45 age range (p0.001) and 44.4% older than 65 years (p0.001). In terms of incidence and mortality rates, men predominated in both groups; however, this pattern was less prominent in aboriginal areas than in non-aboriginal areas.The mortality rates and incidence of TB in aboriginal areas are much higher than those in non-aboriginal areas in Taiwan. Concentration of resources and programs to control TB in aboriginal areas may represent the most effective use of resources for fighting TB.

This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release caused by Staphylococcus aureus lipoteichoic acid (LTA) in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated LTA-induced iNOS expression and NO release. Two PKC inhibitors (Go 6976 and Ro 31-8220), an NF-kappaB inhibitor (pyrrolidine dithiocarbamate; PDTC), and long-term (24 h) 12-phorbol-13-myristate acetate (PMA) treatment each also inhibited LTA-induced iNOS expression and NO release. Treatment of cells with LTA caused an increase in PKC activity; this stimulatory effect was inhibited by D-609, U-73122, or Ro 31-8220. Stimulation of cells with LTA caused IkappaB-alpha phosphorylation and IkappaB-alpha degradation in the cytosol, and translocation of p65 and p50 NF-kappaB from the cytosol to the nucleus. Treatment of cells with LTA caused NF-kappaB activation by detecting the formation of NF-kappaB-specific DNA-protein complexes in the nucleus; this effect was inhibited by Go 6976, Ro 31-8220, long-term PMA treatment, PDTC, L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), and calpain inhibitor I. These results suggest that LTA might activate PC-PLC and PI-PLC to induce PKC activation, which in turn initiates NF-kappaB activation, and finally induces iNOS expression and NO release in RAW 264.7 macrophages.

Stevioside is a natural sweet-tasting glycoside isolated from the herb Stevia rebaudiana, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used commercially as sugar substitute. Previous study has shown that it can lower blood pressure in anesthetized spontaneously hypertensive rats (SHR). This study was undertaken to evaluate the antihypertensive effect of stevioside in different strains of hypertensive rats and to observe whether there is difference in blood pressure lowering effect.Noninvasive tail-cuff method was employed to measure blood pressure. Stevioside at the concentrations of 50, 100 and 200 mg/kg were administered intraperitoneally (ip) to normotensive Wistar-Kyoto rats (NTR), SHR, deoxycorticosterone acetate-salt (DOCA-NaCl) sensitive hypertensive rats (DHR) and renal hypertensive rats (RHR).Significant hypotensive effect of stevioside administered ip was noted in different strains of rats at the dose of 50 mg/kg. When stevioside was increased to the concentrations of 100 and 200 mg/kg, ip, it also caused slow and persistent lowering of blood pressure in SHR and NTR. Data also showed that stevioside given at the concentrations of 100, 200 and 400 mg/kg ip resulted in lowering of blood pressure in SHR dose-dependently. Blood pressure returned to previous levels after the drug was discontinued for 2-3 days. Drinking of 0.1% stevioside solution in mature SHR could have antihypertensive effect and also prevented hypertension in immature SHR.This study reconfirmed stevioside has hypotensive effect and the effect is more prominent in hypertensive rats.