Cannabinoids have been proposed to possess neuroprotective properties; though their mechanism of action remains contentious, they are posited to prevent neurodegenerative disorders, including Parkinson's disease, the pathogenesis of which has not been established. Recent studies have demonstrated that induction of proteasomal dysfunction in animal models results in a phenotype similar to Parkinson's disease. Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2) in dopaminergic neuronal death induced by a proteasomal synthase inhibitor (PSI), additionally testing the hypothesis that WIN55.212.2 modulates cytoplasmic accumulation of parkin and alpha-synuclein, a key feature of proteasomal dysfunction in Parkinson's. WIN55.212.2 protects PC12 cells from PSI-induced cytotoxicity, concomitantly inhibiting PSI-induced polyADP ribose polymerase expression and activation of caspase-3. While PSI induces cytoplasmic accumulation of alpha-synuclein and parkin, WIN55.212.2 counters these effects. Interestingly, however, while PSI induces the activation and nuclear translocalization of nuclear factor kappaB, WIN55.212.2 potentiates this effect. These data are suggestive that WIN55.212.2 might confer a neuroprotective benefit in PSI-induced proteasomal dysfunction, and could further protect against neuronal degeneration stemming from cytoplasmic accumulation of alpha-synuclein and parkin. These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson's disease.
alpha-Synuclein ; Animals ; Cannabinoids ; Caspase 3 ; Cytoplasm ; Dopaminergic Neurons ; Models, Animal ; Neurodegenerative Diseases ; Neurons ; NF-kappa B ; Parkinson Disease ; PC12 Cells ; Phenotype ; Receptors, Cannabinoid ; Ribose

We herein describe a 70-year-old woman who presented with respiratory failure due to extensive lung adenocarcinoma. Despite advanced disease, care in the intensive care unit with ventilator support was performed because she was a newly diagnosed patient and was considered to have the potential to recover after cancer treatment. Because prompt control of the cancer was needed to treat the respiratory failure, empirical treatment with an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was initiated before confirmation of EGFR-mutant adenocarcinoma, and the patient was successfully treated. Later, EGFR-mutant adenocarcinoma was confirmed.
Adenocarcinoma* ; Aged ; Female ; Humans ; Intensive Care Units ; Lung* ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Respiration, Artificial ; Respiratory Insufficiency* ; Ventilators, Mechanical ; Erlotinib Hydrochloride

Purpose: Long-term tracheal stent placement can increase the risk of stent-related complications; hence, removal of the stent after stabilization is attempted. However, little evidence has been established regarding the risk factors for tracheal restenosis. We aimed to identify the risk factors for tracheal restenosis in patients with post-intubation tracheal stenosis (PITS) and post-tracheostomy tracheal stenosis (PTTS). Materials and Methods: We retrospectively analyzed patients with PITS and PTTS between January 2004 and December 2019. Patients were classified into a success or failure group according to treatment outcomes. Patients with successful stent removal were defined as patients who did not require additional intervention after stent removal during the follow-up period. Multiple logistic regression analysis was performed to identify the factors associated with tracheal restenosis. Results: Among 269 stented patients, 130 patients who had removed the stent were enrolled in this study. During the follow-up period, 73 (56.2%) patients had a stable clinical course; however, 57 (43.8%) patients had restenosis. The proportion of trauma-induced intubation was higher in the success group than in the failure group (p=0.026), and the median stent length was shorter in the success group (45 mm) than in the failure group (50 mm, p=0.001). On multivariate analysis, trauma-induced intubation [adjusted odds ratio (aOR), 0.329; 95% confidence interval (CI), 0.117–0.927; p=0.036], and stent length <50 mm (aOR, 0.274; 95% CI, 0.130–0.578; p=0.001) were associated with a decreased risk of restenosis. Conclusion Trauma-induced intubation and stent length were associated with successful stent removal.

Background: After relieving stenosis with an airway silicone stent in post-tuberculosis bronchial stenosis (PTTS), stent removal is attempted if it is determined that airway patency can be maintained even after stent removal. However, the factors affecting airway stent removal are not well known. We investigate the factors that enable the successful removal of airway silicone stents in patients with PTTS. Methods: We retrospectively analyzed PTTS patients who underwent bronchoscopic intervention from January 2004 to December 2019. Successful stent removal is defined as airway patency maintained when the stent is removed, so that reinsertion of the stent is not required. A multivariate logistic regression analysis was used to identify independent factors associated with successful stent removal at the first attempt. Results: Total 344 patients were analyzed. Patients were followed up for a median of 47.9 (26.9–85.2) months after airway stent insertion. Approximately 69% of PTTS patients finally maintained airway patency after the stent was removed. Factors related to successful stent removal at the first attempt were older age and male sex. Absence of parenchymal calcification, segmental consolidation & bronchiolitis, and no trachea involved lesion were relevant to the successful stent removal. Stent dwelling for 12–24 months was associated with successful stent removal compared to a duration of less than 12 months. Conclusion For patients whose airway patency is determined to be maintained even without a stent, it is necessary to attempt stent removal in consideration of factors related to successful stent removal.

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) is a disease with high mortality if left untreated. But, confirmative diagnosis is difficult because many diagnostic modalities are nonspecific. Pulmonary angiography, which is considered as the gold standard diagnostic tool, is invasive, costly, time-consuming, and not always available in small centers. Echocardiography is a non-invasive and available in the emergency room without significant time delay. We investigated the role of echocardiography as a screening test in patients with suspected PE. MATERIALS AND METHODS: (A) Retrospective study: We analyzed the recorded videotapes of transthoracic echocardiography in fifty patients with confirmed PE from Jan 1995 to Aug 1999. From the frequent echocardiographic findings of those patients, positive criteria were defined as followed ( 2 among 1-5 or only 6). (1) RV or pulmonary artery dilatation (RVEDA/LVEDA 0.6) (2) RV hypokinesis (3) paradoxical septal wall motion (4) pulmonary hypertension (5) TR (moderate degree or more) (6) Visible thrombus. Although the degree of TR was less than moderate, if the degree of pulmonary hypertension was more than moderate, we considered as PE. (B) Prospective study: From Nov 1999 to June 2000, patients with suspected pulmonary embolism underwent a transthoracic echocardiography and perfusion-ventilation lung scan or chest CT. We assessed echocardiographic findings, sensitivity and specificity of the previously defined echocardiographic positive criteria for PE. RESULTS: (A) Retrospective study: The sensitivity of echocardiography for PE was 74%. (B) Prospective study: The number of enrolled patients was thirty-four. In twenty patients the diagnosis was PE. The sensitivity of echocardiography was 75% but the specificity was 14%. CONCLUSION: Echocardiography may be used as a good screening test in patients who are clinically suspicious of pulmonary embolism.
Angiography ; Diagnosis ; Dilatation ; Echocardiography* ; Emergency Service, Hospital ; Humans ; Hypertension, Pulmonary ; Lung ; Mass Screening* ; Mortality ; Prospective Studies ; Pulmonary Artery ; Pulmonary Embolism* ; Retrospective Studies ; Sensitivity and Specificity ; Thrombosis ; Tomography, X-Ray Computed ; Videotape Recording

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) is a disease with high mortality if left untreated. But, confirmative diagnosis is difficult because many diagnostic modalities are nonspecific. Pulmonary angiography, which is considered as the gold standard diagnostic tool, is invasive, costly, time-consuming, and not always available in small centers. Echocardiography is a non-invasive and available in the emergency room without significant time delay. We investigated the role of echocardiography as a screening test in patients with suspected PE. MATERIALS AND METHODS: (A) Retrospective study: We analyzed the recorded videotapes of transthoracic echocardiography in fifty patients with confirmed PE from Jan 1995 to Aug 1999. From the frequent echocardiographic findings of those patients, positive criteria were defined as followed ( 2 among 1-5 or only 6). (1) RV or pulmonary artery dilatation (RVEDA/LVEDA 0.6) (2) RV hypokinesis (3) paradoxical septal wall motion (4) pulmonary hypertension (5) TR (moderate degree or more) (6) Visible thrombus. Although the degree of TR was less than moderate, if the degree of pulmonary hypertension was more than moderate, we considered as PE. (B) Prospective study: From Nov 1999 to June 2000, patients with suspected pulmonary embolism underwent a transthoracic echocardiography and perfusion-ventilation lung scan or chest CT. We assessed echocardiographic findings, sensitivity and specificity of the previously defined echocardiographic positive criteria for PE. RESULTS: (A) Retrospective study: The sensitivity of echocardiography for PE was 74%. (B) Prospective study: The number of enrolled patients was thirty-four. In twenty patients the diagnosis was PE. The sensitivity of echocardiography was 75% but the specificity was 14%. CONCLUSION: Echocardiography may be used as a good screening test in patients who are clinically suspicious of pulmonary embolism.
Angiography ; Diagnosis ; Dilatation ; Echocardiography* ; Emergency Service, Hospital ; Humans ; Hypertension, Pulmonary ; Lung ; Mass Screening* ; Mortality ; Prospective Studies ; Pulmonary Artery ; Pulmonary Embolism* ; Retrospective Studies ; Sensitivity and Specificity ; Thrombosis ; Tomography, X-Ray Computed ; Videotape Recording

BACKGROUND: We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli wuggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therfore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. METHODS: Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes(OBM) were stimulated with LPS(10 micrograms/ml), H37Rv, or H37Ra(5X10(5) bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of TNFalpha and IL-1beta production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. RESULTS: TNFalpha and IL-1beta productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in TNFalpha and IL-1beta production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. CONCLUSION: Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.
Blotting, Northern ; Chemokine CCL5 ; Chemokines ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells* ; Healthy Volunteers ; Interleukin-8 ; Monocytes ; Phagocytosis ; RNA, Messenger ; Tuberculosis ; Tuberculosis, Pulmonary ; Tumor Necrosis Factor-alpha ; Virulence*

Primary tracheal amyloidosis (PTA) can lead to airway obstructions, and patients with severe PTA should undergo bronchoscopic interventions in order to maintain airway patency. Focal airway involvements with amyloidosis can only be treated with mechanical dilatation. However, the PTA with diffused airway involvements and concomitant cartilage destructions requires stent placement. Limited information regarding the usefulness of silicone stents in patients with PTA has been released. Therefore, we report a case of diffused PTA with tracheomalacia causing severe cartilage destruction, which is being successfully managed with bronchoscopic interventions and silicone stent placements.
Airway Obstruction ; Amyloidosis* ; Bronchoscopy ; Cartilage* ; Dilatation ; Humans ; Silicones* ; Stents* ; Tracheomalacia

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea syndrome(OSAS) is characterized by repeated apnea, hypopnea, and micro-arousals during sleep. Among various treatment modalities of OSAS, continuous positive airway pressure(CPAP) treatment is the most effective and successful. The aim of this study was to compare efficacy and safety of newly developed Korean CPAP with standard CPAP in OSAS patients. MATERIALS AND METHOD: In total, 20 of 26 recruited OSAS patients completed the study. All subjects first used the standard CPAP for 4 weeks. After an at least 2 week wash-out period, the subjects used the newly developed CPAP for 4 weeks. Polysomnography, questionnaires associated with sleep, lipid profile, pulmonary function test, cardiac marker, and physical examinations were evaluated at baseline and were followed-up after each treatment. RESULTS: After treatment with the newly developed CPAP, the apnea-hypopnea index was decreased from 53.2/hr to 2.5/hr and was equivalent to that of the standard CPAP. Most of the changes in questionnaire scores, laboratory findings, and physical examinations after newly developed CPAP treatment were equivalent to those with standard CPAP. No serious adverse events were observed during the study. CONCLUSION: The efficacy and safety of a newly developed CPAP are equivalent to those of standard CPAP in OSAS patients.
Apnea ; Continuous Positive Airway Pressure* ; Humans ; Methods ; Physical Examination ; Polysomnography ; Respiratory Function Tests ; Sleep Apnea, Obstructive*

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.
Animal ; Blood Cell Count ; Bronchoalveolar Lavage Fluid ; Carbon Dioxide/analysis ; Disease Models, Animal ; Dogs ; Female ; Fluorocarbons/pharmacology* ; Hemodynamics ; Histocytochemistry ; Inflammation/prevention & control ; Lung Diseases/physiopathology* ; Lung Diseases/chemically induced ; Male ; Oleic Acid ; Oxygen/analysis ; Pulmonary Gas Exchange/drug effects* ; Pulmonary Ventilation/physiology* ; Respiratory Function Tests ; Ventilators, Mechanical