Biomedical subjects

Han-Pin Kuo

Publications and source records attributed to Han-Pin Kuo.

At least 19 recordsLinked to original sources

PubMed2006

The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells.

Defensins play a pivotal role in antimicrobial reactions, inflammatory responses, wound repair, and specific immunity. In inflammatory and infectious lung diseases, alpha-defensins are released from recruited neutrophils, and modulate a variety of lung cell functions. We found that human bronchial and alveolar epithelial cells treated with low and moderate concentrations (5 and 10 micro g/ml) of purified neutrophil-derived alpha-defensin-1 secreted more interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 in a dose- and time-dependent manner. Under moderate and high concentrations (10 and 20 micro g/ml) of alpha-defensin-1, we observed typical apoptotic changes in the lung epithelial cells after stimulation for 24 h. Furthermore, alpha-defensin-1 triggered lung cell detachment in a time- and dose-dependent manner at moderate and high concentrations. Prior to the detachment, caspase-3 activity significantly increased. On confocal laser microscopy, rapid translocation of alpha-defensin-1 to the endoplasmic reticulum (ER) was noted. These findings suggest that neutrophil-derived alpha-defensin-1 has pro-inflammatory and apoptotic effects in human bronchial and alveolar epithelial cells, which are concentration-dependent and may be associated with ER activity.

Amino Acid Chloromethyl Ketones↗

PubMed2006

Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.

Adenocarcinoma↗

PubMed2006

Neutrophil-derived elastase induces TGF-beta1 secretion in human airway smooth muscle via NF-kappaB pathway.

Neutrophils are infiltrated in airways of individuals with more severe and chronic asthma, with uncertain significance. Airway smooth muscle (ASM), apart from its contractile properties, is critically involved in the pathogenesis of asthma by producing inflammatory mediators. In the present study, we investigated the impact of neutrophil-derived elastase (NE) on ASM in terms of TGF-beta1 release, and we explored the underlying mechanisms. Primary ASM cells were serum starved for 24 h before stimulation with NE (0.01-0.5 microg/ml). TGF-beta1 in supernatant was determined by ELISA and mRNA quantified by real-time RT-QPCR. NF-kappaB nuclear translocation and activation was examined by Western blotting and kappaB-2 dEGFP reporter gene assay. Association of IL-1 receptor-associated kinase (IRAK) with MyD88 was studied by co-immunoprecipitation and Toll-like receptor 4 (TLR4) determined by FACS scan and Western blotting. We demonstrated that NE enhanced TGF-beta1 release in a time-dependent manner. This induction was inhibited by actinomycin D (5 mM), cycloheximide (5 mM), and NF-kappaB inhibitors, including pyrrolidine dithiocarbamate (PDTC, 1 mM), aspirin (2.5 mM), and sodium salyicylate (2.5 mM). Stimulation with NE was rapidly followed by association of IRAK with MyD88, phosphorylation of IkappaBalpha, and nuclear translocation of p65 with increased transactivation activity. We also found that TLR4 levels were reduced upon NE treatment. These data suggest that NE upregulates TGF-beta1 gene expression and release via My88/IRAK/NF-kappaB pathway, possibly through activation of TLR4, and shed light on a potential role of neutrophils in the pathogenesis of asthma.

Cell Line↗

PubMed2006

Tumor necrosis factor-alpha induces caspase-independent cell death in human neutrophils via reactive oxidants and associated with calpain activity.

Apoptosis mediated by caspase activation is important in the neutrophil homeostasis and resolution of tissue inflammation. Paradoxically, our previous study demonstrated that broad-spectrum caspase inhibition augmented tumor necrosis factor (TNF)-alpha-induced cell death in the human neutrophils. Therefore, we further explored the mechanisms related to the caspase-independent cell death in the neutrophils. The cell apoptosis/necrosis was determined by annexin V and propidium iodide dual staining in flow cytometry. Their morphological changes were observed under light microscopy. Fluorogenic substrates were used to measure the intracellular oxidative reactions and the activities of proteinases, calpains. Calpain inhibitors and antioxidants were used to elucidate the relationship of calpains and oxidants with the neutrophil cell death. Our results verified the caspase-independent cell death pathway in the zVAD-sensitized, TNF-alpha-stimulated neutrophils. Furthermore, the cell death was accompanied with increased calpain and oxidative activities in the cells. Calpain inhibitors, zLLY, as well as anti-oxidants, catalase and DMSO, were able to attenuate the cell death in the zVAD-sensitized, TNF-alpha-induced neutrophils. Pretreating the neutrophils with G-CSF or GM-CSF was not able to reduce the cell death. These results demonstrate that, in human neutrophils, TNF-alpha-induces a caspase-independent cell death signal, which is related to calpain and oxidative activities and cannot be rescued by the growth factor-related signaling mechanism.

Calpain↗

PubMed2006

Six-month nocturnal nasal positive pressure ventilation improves respiratory muscle capacity and exercise endurance in patients with chronic hypercapnic respiratory failure.

BACKGROUND/PURPOSE: This study was designed to investigate the effects of 6 months of nocturnal nasal positive pressure ventilation (NNPPV) on respiratory muscle function and exercise capacity in patients with chronic respiratory failure. METHODS: A prospective, randomized, controlled design was used. Twenty-nine patients with chronic respiratory failure were enrolled and allocated to either the NNPPV (n = 14) or control group (n = 15). Patients in the NNPPV group received bi-level positive pressure ventilation via nasal mask for 6 consecutive months. Arterial blood gas, respiratory muscle assessment and 6-minute walk test (6MWT) were performed before and after the 6-month NNPPV intervention. Respiratory muscle function was assessed using the variables of maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and maximum voluntary ventilation (MVV). RESULTS: Subjects in the NNPPV group showed a significant improvement in blood gas exchange and increased 6-minute walk distance (6MWD) compared to baseline and the control group. The 6MWD was significantly increased from 257.1 +/- 114.1 to 345.2 +/- 109.9 m (34.3%) in the NNPPV group. NNPPV also significantly improved MVV and Pimax relative to baseline. MVV was significantly increased from 19.2 +/- 6.5 to 22.3 +/- 7.1 L/min (16.1%) in the NNPPV group (p < 0.05). Furthermore, there was a significant correlation between the magnitude of MVV improvement and 6MWD change. CONCLUSION: The 6-month NNPPV treatment significantly decreased the partial pressure of carbon dioxide and improved daytime respiratory muscle function, thus contributing to exercise-capacity increase in patients with chronic respiratory failure.

Aged↗

PubMed2006

A modified goal-directed protocol improves clinical outcomes in intensive care unit patients with septic shock: a randomized controlled trial.

We evaluated whether a goal-directed protocol, without measurement of central venous oxygen saturation, would improve survival in medical intensive care unit (ICU) patients with septic shock. This is a prospective, controlled study in a 24-bed medical ICU at a tertiary care hospital. From a total of 241 consecutive patients with septic shock, 224 were randomly assigned to receive therapy with or without a written protocol using central venous pressure, mean arterial pressure, and urine output as therapeutic goals. Baseline characteristics were similar between groups. Implementation of goal-directed therapy caused a more rapid reversal of persistent shock (47 +/- 22.8 vs. 65.4 +/- 32.1 h, P = 0.006) and decreases of ICU (50% vs. 67.2%, P = 0.009) and in-hospital (53.7% vs. 71.6%, P = 0.006) mortality rates compared with non-goal-directed therapy. Patients receiving goal-directed therapy also had less risk for developing central nervous system or renal failure than patients without. Patients with goal-directed therapy received more fluid during the period of persistent shock (136.2 +/- 119 vs. 88.6 +/- 57.7 mL h, P = 0.034) and less delay in vasopressor administration (78 +/- 22.2 vs. 104.4 +/- 29 min, P = 0.001) than patients with non-goal therapy. Implementation of a goal-directed protocol improves survival and clinical outcomes in ICU patients with septic shock. These benefits may arise from adequate fluid resuscitation, earlier vasopressor administration, rapid shock reversal, and protection of major organ function. With central venous oxygen saturation measurement to detect tissue perfusion, the clinical outcomes may be further improved.

Aged↗

PubMed2005

G-protein-coupled receptor agonists differentially regulate basal or tumor necrosis factor-alpha-stimulated activation of interleukin-6 and RANTES in human airway smooth muscle cells.

Using thapsigargin (Tg), an agent that mobilizes calcium by directly emptying intracellular stores, we previously showed that intracellular calcium may play an important role in the regulation of intercellular adhesion molecule (ICAM)-1 gene expression induced by cytokines in human airway smooth muscle (ASM) cells. In the present study, we extended this previous observation by comparing the effect of Tg and other calcium-mobilizing G-protein-coupled receptor (GPCR) agonists on the expression of different pro-inflammatory genes in response to tumor necrosis factor (TNF)-alpha in ASM cells. We found that in resting cells, Tg (10-100 nM) or the bradykinin (BK) (1-10 muM) and thrombin (Thr) (1 U/ml) stimulated interleukin (IL)-6 secretion but had no effect on regulated on activation, normal T cells expressed and secreted (RANTES) levels. More importantly, such calcium-mobilizing agents significantly enhanced TNF-alpha-induced IL-6 secretion while RANTES secretion was abrogated. The use of luciferase-tagged IL-6 and RANTES promoter constructs demonstrated similar effects of Tg on IL-6 and RANTES genes in basal and TNF-alpha-stimulated conditions. The cyclic adenosine monophosphate (cAMP)-dependent pathway plays a minor role in this differential regulation of IL-6 and RANTES genes expression. 2-Aminoethoxydiphenyl borate (APB), a blocker of store-operated calcium channels (SOCs), and bisindolylmaleimide I (Bis I), a broad-spectrum protein kinase C (PKC) inhibitor, inhibited the basal and synergic effects of IL-6 secretion in response to calcium-mobilizing agents and TNF-alpha, but did not prevent the abrogated effect of RANTES secretion. We also found that Go-6976, a selective calcium-dependent PKC isozyme inhibitor, did not inhibit IL-6 secretion in response to GPCR agonist and TNF-alpha; whereas Rottlerlin, a PKC-delta inhibitor, inhibited both Thr- and TNF-alpha-induced expression of IL-6, while BK-induced IL-6 secretion was not affected. Interestingly, TNF-alpha-induced interferon regulatory factor (IRF)-1 activation was significantly inhibited by all calcium-mobilizing agents, BK, Thr and Tg. These results show that calcium-mobilizing GPCR agonists functionally interact with TNF-alpha to differentially regulate pro-inflammatory genes expression in human ASM cells, possibly by involving Tg-sensitive intracellular calcium stores, SOC and PKC.

Blotting, Western↗

PubMed2005

Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS.

BACKGROUND: During the acute phase of severe acute respiratory syndrome (SARS), mononuclear cells infiltration, alveolar cell desquamation and hyaline membrane formation have been described, together with dysregulation of plasma cytokine levels. Persistent high-resolution computed tomography (HRCT) abnormalities occur in SARS patients up to 40 days after recovery. METHODS: To determine further the time course of recovery of lung inflammation, we investigated the HRCT and inflammatory profiles, and coronavirus persistence in bronchoalveolar lavage fluid (BALF) of 12 patients at recovery at 60 and 90 days. RESULTS: At 60 days, compared to normal controls, SARS patients had increased cellularity of BALF with increased alveolar macrophages (AM) and CD8 cells. HRCT scores were increased and correlated with T-cell numbers and their subpopulations, and inversely with CD4/CD8 ratio. TNF-alpha, IL-6, IL-8, RANTES and MCP-1 levels were increased. Viral particles in AM were detected by electron microscopy in 7 of 12 SARS patients with high HRCT score. On day 90, HRCT scores improved significantly in 10 of 12 patients, with normalization of BALF cell counts in 6 of 12 patients with repeat bronchoscopy. Pulse steroid therapy and prolonged fever were two independent factors associated with delayed resolution of pneumonitis, in this non-randomized, retrospective analysis. CONCLUSION: Resolution of pneumonitis is delayed in some patients during SARS recovery and may be associated with delayed clearance of coronavirus, Complete resolution may occur by 90 days or later.

Adolescent↗

PubMed2005

Eosinophils from asthmatics release IL-5 in an autocrine fashion to prevent apoptosis through upregulation of Bcl-2 expression.

Interleukin (IL)-5 plays an important role in maintaining the survival of eosinophils via the specific alpha-subunit of its receptor. Apoptosis, a form of programmed cell death, is thought to represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma. The aim of our present study is to investigate whether IL-5 acts in an autocrine fashion on eosinophil apoptosis in asthmatics. Immunoreactivities of intracellular IL-5 and IL-5 receptor alpha-subunit (Ralpha) were detected uniquely on the eosinophils. The magnitude of IL-5 and IL-5 Ralpha expression on eosinophils was significantly higher in asthmatics than that of normal subjects (p<0.05) determined by flow cytometry. Apoptosis of eosinophils was measured by the propidium iodide staining method and DNA ladder. The percent of apoptotic eosinophils from asthmatics was significantly increased by coincubation with anti-hIL-5 Ralpha Ab (0.1, 0.5, and 2.5 microg/mL) for 1, 2, or 16 hours than was those of corresponding controls (p<0.05, n=8). However, there was no significant effect of anti-hIL-5 Ralpha Ab on eosinophil apoptosis in normal subjects. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2) proteins was significantly inhibited by the anti-hIL-5 Ralpha Ab or antisense IL-5 oligonucleotides in asthmatics (p<0.05, n=8), but there was no significant change in eosinophils from normal subjects. This study demonstrates that eosinophils from asthmatics release IL-5 in an autocrine fashion to act on their own IL-5 receptors in prevention of apoptosis through the upregulation of Bcl-2 expression.

Adult↗

PubMed2005

Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers.

STUDY OBJECTIVES: To assess the effect of ribavirin-induced anemia on the outcome of severe acute respiratory syndrome (SARS). DESIGN: A retrospective observational study. SETTING: Two medical centers in Taiwan. PATIENTS: Forty-four patients with SARS who received ribavirin and 7 patients with SARS who did not receive ribavirin. MEASUREMENTS AND RESULTS: The mean peak C-reactive protein and lactate dehydrogenase levels were higher in SARS patients who were receiving ribavirin therapy than in SARS patients who were not receiving ribavirin therapy. The mortality was also higher, but the difference was not statistically significant. On multivariate analysis, hemoglobin level was an independent prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after therapy with the antiviral drug was started. Patients with a drop in hemoglobin level of > 2 g/dL had a significantly higher mortality rate than the other patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients; 39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%) required a blood transfusion. The mean slope of the hemoglobin decrease was significantly steeper (p = 0.001) in hypoxemic patients with SARS who were receiving ribavirin than in the nonhypoxemic patients with SARS who were receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of 17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died. The combination of hypoxia with anemia was thus significantly associated with a higher mortality (p < 0.001). CONCLUSIONS: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Adult↗

PubMed2004

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

Adenocarcinoma↗

PubMed2004

Human neutrophil-derived elastase induces airway smooth muscle cell proliferation.

Neutrophils and their derived elastase are abundant in chronic inflammatory responses of asthma. This study aimed to investigate the mitogenic effect of elastase on airway smooth muscle (ASM) cells and the implicated signal transduction pathway. Near confluent cultured human ASM cells were treated with human neutrophil elastase (HNE, 0.01 to 0.5 microg/ml) or vehicle for 24 hours with or without extracellular signal-regulated kinase (ERK) inhibitor (PD98059, 30 microM), p38 kinase inhibitor (SB203580, 10 microM) or elastase inhibitor II (100 microg/ml). The ASM cell numbers were counted by a hemocytometer and DNA synthesis was assessed by flowcytometry. Western blots analysis for the expression of ERK, p38 and cyclin D1 was determined. HNE dose-dependently increased ASM cell numbers and the percentage of cells entering S-phase of cell cycle. This response was abolished by neutrophil elastase inhibitors and attenuated by PD98059, but not SB203580. HNE increased ERK phosphorylation and cyclin D1 expression. Pretreatment with PD98059 significantly inhibited elastase-induced cyclin D1 activity. The increased ASM cellular gap and cell shape change by proteolytic activity of HNE may be contributory to ERK activation and therefore cell proliferation. Our results demonstrate that HNE is mitogenic for ASM cells by increasing cyclin D1 activity through ERK signaling pathway.

Asthma↗

PubMed2004

The impact of delirium on the survival of mechanically ventilated patients.

OBJECTIVES: To revalidate a means of assessing delirium in intensive care unit patients and to investigate the independent effect of delirium on the mortality of mechanically ventilated patients. DESIGN: A prospective cohort study. SETTING: A 37-bed medical intensive care unit of a tertiary care hospital. PATIENTS: Subjects were 102 of 131 consecutive mechanically ventilated patients. MEASUREMENTS: All the enrolled patients were assessed for delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Mortality rate were compared between patients with or without delirium, and the predictors of death were investigated. RESULTS: The two CAM-ICU assessors' sensitivities in diagnosing delirium compared with reference standard were 91% and 95%, whereas their specificities were both 98%. They also demonstrated high interrater reliability with kappa statistics of 0.91. Delirium was present in 22 of 102 (22%) patients in the first 5 days. The delirious patients had higher intensive care unit mortality rate than nondelirious patients (63.6% vs. 32.5%, respectively), with a hazard ratio of 2.57 (95% confidence interval, 1.56-8.15). In multivariate analysis, delirium (odds ratio, 13.0; 95% confidence interval, 2.69-62.91), shock (odds ratio, 12.91; 95% confidence interval, 2.93-56.92), and illness severity (odds ratio, 9.61; 95% confidence interval, 2.24-41.18) were independent predictors of mortality. CONCLUSIONS: This study confirms previous work showing that delirium is an independent predictor for increased mortality among mechanically ventilated patients.

APACHE↗

PubMed2004

Diagnostic value of endobronchial ultrasound-guided transbronchial lung biopsy in peripheral lung cancers.

BACKGROUND AND PURPOSE: The diagnostic yield of flexible fiberoptic bronchoscopy for peripheral lung cancers is still limited. This study evaluated whether endobronchial ultrasound (EBUS) may help localize and improve the diagnostic yield of bronchoscopic transbronchial lung biopsy in peripheral lung cancer. METHODS: Between July 2001 and May 2002, 218 patients received transbronchial lung biopsy during bronchoscopic examinations with (n = 122) or without EBUS guidance (n = 96) and had the presence of peripheral lung cancers subsequently confirmed. These 218 patients were included in this retrospective analysis. RESULTS: The diagnostic accuracy of transbronchial lung biopsy was significantly increased under EBUS guidance for small cell carcinoma (65.6%) and for non-small cell carcinoma (42.7%) [p < 0.01]. For peripheral lung cancer either smaller than 2 cm or larger than 2 cm, the diagnostic yield of transbronchial lung biopsy with EBUS guidance was significantly higher (66.0% vs 42.3%, p < 0.002 for mass larger than 2 cm; 54.5% vs 0%, p < 0.04 for mass smaller than 2 cm). EBUS provided a better diagnostic yield (p = 0.014; odds ratio, 0.219) for lesions localized at the left upper lobe, which are generally thought to be more difficult to approach through bronchoscopy. There were no significant differences in complications between patients who underwent bronchoscopy with or without EBUS guidance. CONCLUSIONS: Under EBUS guidance, the diagnostic yield of transbronchial lung biopsy in peripheral lung cancer by bronchoscopic examination was significantly improved without difference in the complication rate.

Adult↗

PubMed2004

Efficacy of nocturnal nasal positive pressure ventilation in hypercapnic patients with severe obstructive lung diseases.

BACKGROUND: The study objective was to investigate the efficacy of 6 months of nocturnal nasal positive pressure ventilation (NNPPV) on arterial blood gas, exercise capacity, respiratory muscle function, and the frequency of hospital admission in hypercapnic patients with severe obstructive lung diseases. METHODS: This was a prospective, randomized, controlled study. Twenty-seven patients with hypercapnic obstructive lung diseases were randomized to either the NNPPV group (N = 13) or the control group (N = 14). Arterial blood gas, exercise capacity and respiratory muscle function were measured before and after 6 months of NNPPV intervention. The number of hospital admissions and the length of stay during the 6-month period before and after NNPPV intervention were recorded. RESULTS: Subjects in the NNPPV group showed a significant reduction in arterial carbon dioxide partial pressure (PaCO2). bicarbonate (HCO3-), and base excess (BE), compared with those before intervention and of the control group. Six-minute walk distance (6MWD) also increased significantly from 232.2 +/- 79.3 m to 333.4 +/- 81.3 m in the NNPPV group after 6 months of intervention. The maximum voluntary ventilation (MVV) also increased significantly after NNPPV intervention. Moreover, the NNPPV group had significantly lower frequency of admission and fewer days of hospital stay during the intervention period compared with those before intervention and of the control group. CONCLUSION: Six months of NNPPV improved the arterial blood gas, increased exercise capacity and respiratory muscle endurance, and helped to reduce the frequency and the length of hospitalization in hypercapnic patients with severe obstructive lung disease.

Exercise Tolerance↗

PubMed2004

The effects of ciprofloxacin on chest radiographic regression in patients with drug intolerance or resistant tuberculosis.

BACKGROUND: The aim of this study was to identify the clinical efficacy of ciprofloxacin as a second-line anti-tuberculosis agent in pulmonary tuberculosis patients with drug intolerance or resistance. METHODS: There were 20 patients with drug related adverse effects or drug resistance enrolled in the ciprofloxacin treatment group (CG). There were also 32 patients enrolled in the non-ciprofloxacin treatment group (NCG) that maintained conventional drug regimens or the addition of other drugs like streptomycin. The radiographic presentation was evaluated using score grading. The speed and outcome of regression in the chest radiographic presentations were also evaluated. RESULTS: Data showed the CG had significantly more rapid regression than the NCG in drug-resistant patients (p < 0.01). For the adversely effected patients in the CG, the mean scores of pre- and post-treatment were 3.1+/-0.2 and 2.2+/-0.3 (p < 0.001), respectively. For the adversely effected patients in the NCG, the mean score of pre-treatment was 3.7+/-0.4 and post-treatment mean score was 3.0+/-0.4 (p < 0.05). For the drug-resistant patients in the CG, the mean scores of pre- and post-treatment were 4.3+/-0.4 and 3.4+/-0.5 (p < 0.05), respectively. For the drug-resistant patients in the NCG, the mean score of pre-treatment was 3.7+/-0.3 and post-treatment mean score was 3.2+/-0.3 (no significant difference). Obviously, the CG had the same effects compared with the NCG in adverse-effect group. On the other hand, the CG had the tendency of more rapid radiographic regression and better radiographic outcomes than the NCG in drug-resistant patients. CONCLUSIONS: Ciprofloxacin provides a better option for second-line drug treatment for pulmonary tuberculosis when patients cannot use conventional anti-tuberculosis agents.

Adult↗

PubMed2003

Endogenous nitric oxide downregulates the Bcl-2 expression of eosinophils through mitogen-activated protein kinase in bronchial asthma.

BACKGROUND: Eosinophil apoptosis might play a crucial role in the maintenance of persistent airway inflammation in asthma. Nitric oxide (NO) synthase activity is upregulated in eosinophils of asthmatic patients. Mitogen-activated protein kinase (MAPK) is implicated in regulating eosinophil apoptosis by modulating Bcl-2 expression. NO-induced cell apoptosis is associated with an inhibition of Bcl-2 expression. OBJECTIVE: We sought to study whether NO might induce eosinophil apoptosis through extracellular signal-regulated protein kinase (ERK) or p38 MAPK pathways and Bcl-2 expression. METHODS: Eosinophils were freshly isolated from peripheral blood of 16 asthmatic patients and 12 healthy subjects and then cultured with or without the NO synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) at 1 and 10 mmol/L for 16 hours. The expression of Bcl-2 and induced NO synthase on eosinophils was analyzed by means of flow cytometry. Apoptosis was assessed by means of propidium iodide and DNA ladder. The activity of ERK and p38 MAPK was determined by means of Western blotting. RESULTS: The induced NO synthase immunoreactivities and the spontaneous release of nitrite from the eosinophils of asthmatic patients were higher compared with those of healthy subjects. Eosinophils of asthmatic patients were found to express more highly constitutive Bcl-2 than those of healthy subjects. After incubation for 16 hours, the expression of Bcl-2 on eosinophils from patients with asthma was significantly enhanced by L-NAME. The percentage of apoptosis was decreased by the addition of 1 mmol/L L-NAME in patients with asthma. The activity of p38 MAPK and ERK in eosinophils from patients with asthma was enhanced in the presence of L-NAME. An inhibition of MAPK reduced the Bcl-2 expression and increased eosinophil apoptosis in patients with asthma. CONCLUSION: We concluded that inhibition of endogenous NO might increase the expression of Bcl-2 in eosinophils from patients with asthma through the signaling pathway of ERK or p38 MAPK, which in turn decrease the apoptosis.

Adult↗

PubMed2003

Effect of theophylline and specific phosphodiesterase IV inhibition on proliferation and apoptosis of progenitor cells in bronchial asthma.

1. Theophylline possesses anti-inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells. 2. Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM-CSF, stem cell factor, IL-3 and IL-5. Apoptosis was measured by flow cytometry of propidium-iodide-stained cells. 3. A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown. Theophylline (at 5 and 20 micro g ml(-1)) significantly inhibited colony formation and increased apoptotic cells in asthmatics compared to control. Salbutamol (0.1, 1, 10 micro M), dibutyryl-cAMP (0.1, 1 mM) and rolipram (0.1, 1 mM), a phosphodiesterase IV inhibitor, also dose-dependently decreased colony numbers and increased apoptosis of progenitor cells from asthmatics. 4. There was no significant effect of theophylline, db-cAMP, salbutamol or rolipram on colony formation or the survival of progenitor cells from normal subjects. AMP did not affect the colony formation and apoptosis. Expression of Bcl-2 protein on progenitor cells of asthma was downregulated by theophylline, salbutamol, db-cAMP and rolipram. 5. Theophylline and rolipram decreased colony formation committed to the eosinophil lineage, together with an increase in apoptosis through an inhibition of Bcl-2 expression effects that may occur through cAMP. The anti-inflammatory properties of theophylline include an inhibition of circulating progenitor cells.

Albuterol↗