• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.522-531
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• 2003

Background : Hemorrhagic shock and trauma are two of the most common causes of acute lung injury. The activation of cyclooxygenase is one of the important causes of acute lung injury. This study investigated the effect of aspirin, a well-known cyclooxygenase inhibitor, on severe hemorrhage-induced acute lung injury in rats. Methods : The hemorrhagic shock was induced by withdrawing blood; 20ml/kg of B.W., through the femoral artery in 5 min. The mean arterial pressure was recorded through the femoral artery on a polygraph. Results : In the present investigation, the lung tissue myeloperoxidase activity, protein contents and leukocyte counts, in bronchoalveolar lavage fluid, increased significantly 2 and 24 h after the hemorrhage induction. Although the decreased mean arterial pressure spontaneously recovered, acute lung injury occurred after severe hemorrhage. These changes were effectively prevented by a single intravenous injection of aspirin (10 mg/kg of B.W.) 30 min before the hemorrhage. Conclusion : These results suggest that severe hemorrhage-induced acute lung injury is mediated, in part, by the activation of cyclooxygenase. Furthermore, pretreatment of aspirin in acute lung injury-prone patients, or prophylactic treatment of aspirin to the patients with precipitating conditions, could be helpful in the prevention of acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.70 no.1
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• pp.21-27
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• 2011

Background: Although the gold standard method for research trials on epidermal growth factor receptor (EGFR) mutations has been direct sequencing, this approach has the limitations of low sensitivity and of being time-consuming. Peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping is known to be a more sensitive detection tool. The aim of this study was to compare the detection rate of $EGFR$ mutation and EGFR-tyrosine kinase inhibitor (TKI) responsiveness according to $EGFR$ mutation status using both methodologies. Methods: Clinical specimens from 112 NSCLC patients were analyzed for $EGFR$ mutations in exons 18, 19, 20, and 21. All clinical data and tumor specimens were obtained from 3 university hospitals in Korea. After genomic DNA was extracted from paraffin-embedded tissue specimens, both PNA-mediated PCR clamping and direct-sequencing were performed. The results and clinical response to $EGFR$-TKIs were compared. Results: Sequencing revealed a total of 35 (22.9%) mutations: 8 missense mutations in exon 21 and 26 deletion mutations in exon 19. PNA-mediated PCR clamping showed the presence of genomic alterations in 45 (28.3%) samples, including the 32 identified by sequencing plus 13 additional samples (6 in exon 19 and 7 in exon 21). Conclusion: PNA-mediated PCR clamping is simple and rapid, as well as a more sensitive method for screening of genomic alterations in $EGFR$ gene compared to direct sequencing. This data suggests that PNA-mediated PCR clamping should be implemented as a useful screening tool for detection of $EGFR$ mutations in clinical setting.

• Tuberculosis and Respiratory Diseases
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• v.69 no.6
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• pp.418-425
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• 2010

Background: Little is known about the long-term effects of angiotensin-converting enzyme (ACE) treatment on post-tuberculosis emphysema. This study evaluated the effects of ACE inhibition on cardiac function and gas exchange in patients with post-tuberculosis emphysema. Methods: At baseline and at 6 months after initiation of ACE inhibition therapy, patients underwent pulmonary function testing, arterial blood gas analysis, and echocardiography, both at rest and post exercise. Cardiac output (CO) and right ventricular ejection fraction (RVEF) were measured at those time points as well. Results: After ACE inhibition; resting and post-exercise RVEF ($Mean{\pm}SEM,\;61.5{\pm}1.0,\;67.6{\pm}1.2%$, respectively) were higher than at baseline ($56.9{\pm}1.2,\;53.5{\pm}1.7%$). Resting and post-exercise CO ($6.37{\pm}0.24,\;8.27{\pm}0.34L/min$) were higher than at baseline ($5.42{\pm}0.22,\;6.72{\pm}0.24L/min$). Resting and post-exercise $PaO_2$ ($83.8{\pm}1.6,\;74.0{\pm}1.2mmHg$, respectively) were also higher than at baseline ($74.2{\pm}1.9,\;66.6{\pm}1.6mmHg$). Post-exercise $PaCO_2$($46.3{\pm}1.1mmHg$) was higher than at baseline ($44.9{\pm}1.1;\; Resting\;42.8{\pm}0.8\;vs.\;42.4{\pm}0.9mmHg$). Resting and post-exercise A-a $O_2$ gradient ($12.4{\pm}1.4,\;17.8{\pm}1.5 mmHg$) were lower than at baseline ($22.5{\pm}1.5,\;26.9{\pm}1.6mmHg$). Conclusion: In post-tuberculosis emphysema, RVEF and CO were augmented with a resultant increase in peripheral oxygen delivery after ACE inhibition. These findings suggest that an ACE inhibitor may have the potential to alleviate co-morbid cardiac conditions and benefit the patients with post-tuberculosis emphysema.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.133-142
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• 2019

Background: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. Methods: Mouse AE II cell line MLE-12 were exposed to $1-10{\mu}g/mL$ BLM and $0.01-100{\mu}M$ baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. Results: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor ${\alpha}$, and transforming growth factor ${\beta}1$. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. Conclusion: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.25 no.1
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• pp.12-21
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• 2012

Background and Objectives : Allergic rhinitis is one of the most common diseases in the otorhinolaryngology area. in oriental clinic, Hyunggaeyungyo-tang(HYT) has been used as a primary prescription to treat allergic rhinitis. However, there have been no studies so far performed on the effect of this HYT use. The purpose of this study was find out therapeutic effects of its exclusive use on the rat with allergic rhinitis. Material and Methods : Thirty BALB/c mice were divided into three group : normal group(NOR), control group(CON) inoculated with allergic rhinitis and sample group(SAM) treated with the HYT extract after it was treated the same as the control group. Rats were sensitized intraperitoneally with ovalbumin solution 4times at intervals of 2 days. After that time, rats in SAM were administered by HYT to treat the inflammation. Results : 1. The number of eosinophil in SAM noticeably decreased than CON and this decrease had probability. The inhibition of eosinophil distribution. The infiltration of eosinophil in SAM noticeably decreased than CON. 2. The damaged mucosa as disruption of cilia in respiratory cell, vacant mucose secreting cell and infiltration of inflammation intricate cells in CON were increased than NOR, but SAM same as normal configuration. Decrease of icthing and sneezing intricate neurotransmitter (substance P). Decrease of angiogenesis intricate cytokine(MIP-2). 3. Transcription factor(NF-${\kappa}B$ p65) was decreased. 4. Transcription factor inhibitor(p-$I{\kappa}B$) was decreased. 5. Inflammation cytokine(iNOS) was decreased. Conclusion : The results suggest that HYT is significantly effective in the treatment of inflammation caused by allergic rhinitis through the suppression of NF-${\kappa}B$ activation and iNOS production.

• Journal of Embryo Transfer
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• v.25 no.1
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• pp.35-42
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• 2010

Many studies propose that dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I) is associated with neurodegenerative disorders, such as Parkinson's disease and Huntington's disease. Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. With a recombinant adeno-associated virus vector carrying the NDI1 gene (rAAV-NDI1) as the gene delivery method, we were able to attain high transduction efficiencies even in the human epithelial cervical cancer cells that are difficult to transfect by lipofection or calcium phosphate precipitation methods. Using a rAAV-NDI1, we demonstrated that the Ndi1 enzyme is successfully expressed in HeLa cells. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced HeLa cells were not affected by rotenone which is inhibitor of complex I, but was inhibited by flavone and antimycin A. The NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. In particular, in the NDI1-transduced cells, the yeast enzyme becomes integrated into the human respiratory chain. It is concluded that the NDI1 gene provides a potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.327-334
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• 2017

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established $Ca^{2+}$ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular $Ca^{2+}$ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular $Ca^{2+}$ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than $10{\mu}m$, induced intracellular $Ca^{2+}$ signaling, which was mediated by extracellular $Ca^{2+}$. The PM10-mediated intracellular $Ca^{2+}$ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.1
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• pp.27-31
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• 2000

Characteristics of ethanol production by a xylose-fermenting yeast, Pichia stipitis Y-7124, were studied. The sugar consumption rate and specific growth rate were higher in the glucose-containing medium than in the xylose-containing medium. Specific activities of xylose reductase and xylitol dehydrogenase were higher in the medium with xylose than glucose, suggesting their induction by xylose. Maximum specific growth rate and ethanol yield were achieved at 30 g xylose/L concentration without formation of by-products such as xylitol and acetic acid whereas a maximum ethanol concentration was obtained at 130 g/L xylose. Adding a respiratory inhibitor, rotenone, increased a maximum ethanol concentration by $10\%$ compared with the control experiment. In order to evaluate the pattern of ethanol inhibition on specific growth rate, a kinetic model based on Luong's equations was applied. The relationship between ethanol concentration and specific growth rate was hyperbolic for glucose and parabolic for xylose. A maximum ethanol concentration at which cells did not grow was 33.6 g/L for glucose and 44.7 g/L for xylose.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.5
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• pp.647-653
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• 2015

A 12-wk feeding trial was conducted to evaluate the essentiality of choline supplementation in diets for parrot fish. Five isonitrogenous and isocaloric diets were supplemented with 0 (as control), 500, 1,000, and 2,000 mg choline per kg diet, and a positive control diet without choline contained 0.3% of 2-amino-2-methyl-1-propanol as choline biosynthesis inhibitor (designated as Con, C500, C1000, C2000 and $Con^+$, respectively). Triplicate groups of fish (body weight, $8.8{\pm}0.01g$) were fed one of the experimental diets at a rate of 4% body weight twice daily. The fish fed $Con^+$ diet revealed significantly lower growth performance and feed utilization efficiency than other fish groups. Supplementation of choline to the basal diet did not significantly influence fish growth. The highest liver lipid content was observed in fish fed the $Con^+$ diet and inversely correlated with liver choline concentration although the differences were not significant. Also, significantly higher liver linoleic, eicosapentaenoic and docosahexaenoic acid contents were found in fish fed the $Con^+$ diet. Innate immune parameters including respiratory burst and myeloperoxidase activities were not significantly affected by dietary choline levels. The findings in this study conclude that choline concentration of approximately $230mgkg^{-1}$ diet meets the requirement of parrot fish.