Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling.BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M₂ and M₃ receptors were examined.Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M₂ but decreased expression of M₃ in all aged groups of OVA.Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M₃ and M₂ muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.
ABSTRACT Objective: The tyrosine kinase inhibitor nilotinib has potent inhibitory activity against the stem cell growth factor receptor c-Kit and platelet-derived growth factor receptor (PDGFR). The present study aimed to determine whether nilotinib suppresses airway remodeling and whether its effect is associated with the c-Kit and PDGFR pathways. We also aimed to compare the effect of nilotinib and imatinib on remodeling.We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with nilotinib or imatinib during the OVA challenge.Compared with control mice, the mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, airway hyperresponsiveness (AHR), and exhibited features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of nilotinib significantly inhibited eosinophilic inflammation, AHR, and remodeling in mice chronically exposed to OVA. Nilotinib showed a trend of more potent effect than imatinib on attenuating remodeling in hydroxyproline assay and smooth muscle staining. Nilotinib treatment significantly reduced the expression of phosphorylated (p)-c-Kit, p-PDGFRβ, and p-extracellular signal-regulated kinase 1/2. The expression levels of the genes encoding c-Kit and PDGFRβ were also reduced by nilotinib treatment. Treatment with nilotinib did not affect significantly the level of OVA-specific IgE and IgG1 in serum. In vitro, nilotinib significantly inhibited cell proliferation of fibroblast.These results suggest that nilotinib administration can prevent airway inflammation, AHR, and airway remodeling associated with chronic allergen challenge.
The efficacy of the combination vaccine of the individual C-terminal fragments of ApxIA, ApxIIA and ApxIIIA of Actinobacillus pleuropneumoniae (APP) was evaluated in piglets.Twenty piglets were divided equally into 2 groups (n=10).All piglets were intramuscularly primed at 4 week-of-age (0 week post prime inoculation (WPPI)) and were intramuscularly boosted at 6 week-of-age (2 WPPI).Group A piglets were inoculated with sterile PBS and group B piglets were inoculated with the combination vaccine.Concentrations of each of the C-terminal fragment-specific IgG as determined by ELISA were significantly higher in group B than in group A from 2 WPPI until the end of this study.Clinical signs were observed from only 10% of group B piglets after the challenge with the mixture of APP serotypes 1, 2 and 5 at 4 WPPI, while 50% of group A piglets were protected against APP infections.Overall, intramuscular inoculation with the vaccine candidate can efficiently protect piglets against APP infection.
Abstract Background: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea.Methods: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns.Results: Among the 4,417 cases investigated, 179 (4.1%), 53 (1.2%), and 316 (7.2%) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were similar among the three groups (11.2%, 12.2%, and 10.4% in the younger, middle, and older groups, respectively). MDR/RR-TB case numbers decreased significantly as age increased (8.6%, 6.3%, 3.3%, respectively). Proportions of MDR/RR-TB among retreated patients in the younger generation decreased from 50.0% to 18.2%, but remained higher than that in the older generation. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups.Conclusions: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.
Background: Asthma is characterized by airway inflammation and remodeling. Roflumilast is a selective phosphodiesterase-4 (PDE4) inhibitor that has anti-inflammatory effect in chronic obstructive pulmonary disease (COPD). However, little is known regarding the effect of roflumilast in chronic asthma. This study is aimed to evaluate the effects of roflumilast on airway inflammation and remodelling in a murine model of chronic asthma. Methods: Female BALB/c mice, 6 weeks of age, were used. We developed a mouse model of airway remodeling in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Roflumilast was administered orally starting on the 38th and 5 days a week thereafter for 3 months during the intranasal OVA challenge. A lung fibroblast cell line was used in the proliferation assay. Results: Compared with control mice, mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, airway hyperresponsiveness (AHR), and exhibited features of airway remodeling. Administration of roflumilast significantly inhibited eosinophilic inflammation and AHR. The levels of interleukin (IL)-4, IL-5, and IL-13 in the bronchoalveolar lavage (BAL) fluids were significantly lower in the roflumilast group. The level of hydroxyproline was also significantly lower in the roflumilast group. In vitro, roflumilast significantly inhibited stem cell factor (SCF) induced cell proliferation of fibroblasts. Conclusions: These results suggest that roflumilast administration modulates the airway inflammation, AHR, and airway remodeling associated with chronic allergen challenge.
Intussusception primarily occurs in children and is uncommon in adults. Moreover, intussusception caused by intestinal tuberculosis is very rare. We report a case of intussusception induced by intestinal tuberculosis. A 53-year-old man presented to our hospital with complaints of cough and sputum for 2 weeks. We started anti-tuberculosis medication as the patient’s sputum acid-fast staining was positive. After 4 days of treatment, the patient developed abdominal cramping pain. Imaging studies showed ileo-ileal type intussusception. The patient underwent segmental resection of the small bowel and intestinal tuberculosis was confirmed on histological examination. He recovered after surgery and was discharged on anti-tuberculosis medication.
Abstract Background Active pulmonary tuberculosis (TB) occasionally coexists with lung cancer. However, the clinical and radiologic characteristics of this cooccurrence have not been fully evaluated. Methods Patients diagnosed with lung cancer and active pulmonary TB from January 2009 to December 2017 in four hospitals of the Catholic University of Korea were retrospectively reviewed. The clinical characteristics, including the TB diagnosis methods, lung cancer pathology, staging, initial radiographic features, and survival were analyzed and compared to 575 lung cancer patients without active pulmonary TB from the same hospitals. Results Forty-eight (0.48%) of the 9,936 lung cancer patients had active pulmonary TB confirmed by positive culture results or polymerase chain reaction analysis for M. tuberculosis at the time of the initial cancer diagnosis. The majority of the patients (95.9%) had non-small cell lung cancer and 56.2% of the lung cancers were located in the both upper lobes. In the initial computed tomography, the most frequent findings were a mass-like lesion (79.2%) and separate nodules (75%). When compared to lung cancer patients without TB, the body mass index (BMI) was lower (21.4 vs. 23.1, P = 0.001) in patients with TB. Moreover, the lung cancer patients with TB had advanced clinical stages compared to patients without TB; T3-4 (70.9% vs. 50.6%, P = 0.002), N2-3 (85.2% vs. 55.6%, P < 0.001); M1 (65.9% vs. 44.5%, P = 0.007). Patients' age, histology, location, and the presence of epidermal growth factor receptor mutations were not statistically different between the two groups. Interestingly, lung cancer with TB was associated with lower mortality (hazard ratio = 0.35, 95% CI: 0.2 1– 0.60). Conclusions Rarely diagnosed concurrent active tuberculosis in lung cancer patients was associated with lower BMI and advanced clinical stages. Active investigation of and treatment for active pulmonary TB in lung cancer patients could improve patient outcomes.
Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. There is emerging interest in the involvement of the transient receptor potential vanilloid 1 (TRPV1) channel in the pathophysiology of asthma. This study examined whether TRPV1 antagonism alleviates asthma features in a murine model of chronic asthma.BALB/c mice were sensitized to and challenged by ovalbumin to develop chronic asthma. Capsazepine (TRPV1 antagonist) or TRPV1 small interfering RNA (siRNA) was administered in the treatment group to evaluate the effect of TPV1 antagonism on AHR, airway inflammation, and remodeling.The mice displayed increased AHR, airway inflammation, and remodeling. Treatment with capsazepine or TRPV1 siRNA reduced AHR to methacholine and airway inflammation. Type 2 T helper (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13) were reduced and epithelial cell-derived cytokines (thymic stromal lymphopoietin [TSLP], IL-33, and IL-25), which regulate Th2 cytokine-associated inflammation, were also reduced. Airway remodeling characterized by goblet cell hyperplasia, increased α-smooth muscle action, and collagen deposition was also alleviated by both treatments.Treatment directed at TRPV1 significantly alleviated AHR, airway inflammation, and remodeling in a chronic asthma murine model. The TRPV1 receptor can be a potential drug target for chronic bronchial asthma.
This study examines the impact of COVID-19 on education gap and the effectiveness of response policies through a review of previous research. Based on this, the study presented a causal loop diagram illustrating the cyclical patterns of learning loss caused by COVID-19 across different socio-economic strata. The initiation of remote teaching led to learning deficiencies in lower-income groups, resulting in academic declines and widening educational gaps with higher-income counterparts. To prevent a recurrence of such deepening educational gaps in future disasters, the study proposed policy alternatives in three dimensions: 1) Establishment of policies addressing the fundamental resolution of self-care time, 2) Vision formulation for media literacy education targeting students and parents, and 3) Development of personalized learning content.
Abstract Background and objective Peptide nucleic acid ( PNA )‐mediated real‐time polymerase chain reaction clamping was recently developed to improve mutation detection sensitivity. Pleural effusion could be a good sample candidate for mutation analysis. To establish if PNA clamping could be used to detect KRAS mutation in particular in pleural effusion, we analysed its diagnostic performance. Methods We studied 57 patients with malignant effusion. KRAS mutation was evaluated in samples of matched tumour tissue, cell block, pleural effusion and serum using PNA clamping and direct sequencing. Results The detection rate of KRAS mutation using pleural effusion was 14% for PNA clamping and 10.5% for direct sequencing. The κ coefficient between the two methods was 0.76 ( P value < 0.0001), 1.00 ( P value < 0.0001) and 0.87 ( P value < 0.0001) in pleural effusion, tissue and cell block, respectively. The diagnostic performance of KRAS mutation detection from pleural effusion compared with the results obtained for all samples combined showed that the sensitivity, specificity, positive predictive value and negative predictive value were as follows: 89, 100, 100 and 98%, respectively for PNA clamping; 67, 100, 100 and 94%, respectively for directing sequencing. Conclusions The current study suggests that PNA clamping had a good concordance with direct sequencing for the detection of KRAS mutation in patients with malignant effusion. Furthermore, the good diagnostic performance obtained from pleural effusion samples provides evidence that pleural effusion can be a useful source for detecting KRAS mutation in a clinical setting, in which the collection of tumour tissues is challenging.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)