Background: Mycobacterium tuberculosis is a facultative intracellular pathogen which persists and multiplies within macrophage. Competent cell mediated immunity by cooperation of both T lymphocyte and macrophage of the host is required to kill the Mycobacterium tuberculosis. But a precise understanding of the pathogenesis of tuberculosis infection in pulmonary alveolar macrophage has not been achived. Research on the macrophage's basic microbicidal mechanism has elucidated the importance of oxygen-dependent or oxygen-independent components. Oxygen dependent processing begins with the reduction of oxygen by NADPH oxidase and generation of superoxide. In this study, the oxidative metabolic status of blood monocyte and pulmonary alveolar macrophage in patients with active pulmonary tuberculosis was accessed and compared with that of healthy control subjects to know whether there was a basic difference in superoxide generation by mononuclear cells between two groups. Methods: Pulmonary alveolar macrophage was purified after performing BAL(bronchoalveolar lavage) through the bronchi of infected lesion by plastic adhesion method. Blood monocyte was purified by Ficoll-Hypaque method. Superoxide generation by blood monocyte and pulmonary alveolar macrophage was measured by ferricytochrome-C reduction method after either stimulated with PMA(phorbol myristate acerate) or non-stimulated states. We also measured the effect of pulmonary tuberculosis patient's serum on superoxide generation by monocyte. Results: 1) Generation of superoxide by alveolar macrophage obtained from patients with pulmonary tuberculosis was little higher than those of controls, and PMA enhanced the generation of 2) Generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis was little higher than those of control(p>0.05), and PMA more enhanced the generation of superoxide in patientswith pulmonary tuberculosis than those in controls(p<0.02). 3) Patient's serum enhanced the generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis and controls, but not in the case of PMA stimulated blood monocyte. Conclusion: The present study suggest that the phenomenon of M.tuberculosis escape the microbicidal action of macrophage was not result of suppressed superoxide generation by blood monocyte and pulmonary alveolar macrophage, rather there might be a factor to stimulate the generation of superoxide by blood monocyte in pulmonary tuberculosis patient serum, but the comparision with effect of control's serum on superoxide generation needs further elucidation.
Park, Sang-Dong;Kim, Min-Jeong;Lee, A-Ram;Jang, Jun-Hyouk;Kim, Kyung-Ho
Journal of Acupuncture Research
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v.19
no.2
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pp.51-64
/
2002
We have compared(using the same series of experimental tissue samples) the levels of proteolytic enzyme activities and free radical-induced protein damage in synovial fluid from RA and CPH cases. Many protease types showed significantly increased (typically by a factor of approximately 2-3-fold) activity in RA, compared to normal rats. However, CPH significantly reduced the cytoplasmic enzyme activities of arginyl aminopeptidase, leucyl aminopeptidase, pyroglutamyl aminopeptidase, tripeptidyl aminopeptidase, and proline endopeptidase to almost about 1/10 each. For the Iysosomal proteases, synovial fluid samples from RA rats, CPH significantly reduced the enzyme activities of cathepsin B, dipeptidyl aminopeptidase I and dipeptidyl aminopeptidase II. In extracellular matrix degrading(collagenase, tissue elastase) and leukocyte as sociated proteases (leukocyte elastase, cathepsin G), CPH decreased these enzyme activities of collagenase, tissue elastase and leukocyte associated elastase in RA. In cytoplasmic and lysosomal protease activities in plasma from RA. CPH and normal plasma samples were not significantly different, suggesting that altered activity of plasma proteases (particularly those enzymes putatively involved in the immune response) is not a contributory factor in the pathogenesis of RA. In addition, the level of free radical induced damage to synovial fluid proteins was approximately twice that in RA, compared with CPH. CPH significantly decreased the level of ROS induced oxidative damage to synovial fluid proteins (quantified as protein carbonyl derivative). Therefore we conclude that both proteolytic enzymes and free radicals are likely to be of equal potential importance as damaging agents in the pathogenesis of inflammatory joint disease, and that the design of novel therapeutic strategies for patients with the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of protease mechanistic types (i.e. cysteine-, metallo- and serine- proteinases and peptidases). However, increased protein damage induced by ROS could not be rationalised in terms of compromised antioxidant total capacity, since the latter was not significantly altered in RA synovial fluid or plasma compared with CPH.
Purpose: Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS) and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR) in mouse model of asthma. Methods: Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA), LPS or $1.0{\mu}g$ LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL) fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; $P$ values for significance were set to 0.05. Results: Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL)-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion: These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic responses to OVA in this mouse model of astham. Our data show that early life exposure with OVA and/or LPS may have a protective role in the development of allergic airway inflammation and development of allergen-induced airway responses in mouse model of asthma.
Kim, Dae-Woon;Shin, Hee-Jung;You, Tae-Min;Noh, Gyeong-Woon;Kim, Hyun-Joo
The Korean Journal of Nuclear Medicine Technology
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v.15
no.1
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pp.101-105
/
2011
Purpose: Estradiol in the menstrual cycle and ovulation induction as an important test of currently national nuclear medicine laboratory in the normal patients and patients with infertility tests are being performed. For the diagnosis of menopause is an important test with follicle stimulating hormone (FSH) and Luteinizing hormone (LH). Currently participating in external quality control of the nation's hospitals that is 54 percent of 37 hospitals, 20 hospitals have been using A's reagent. The kit's test results are highly different from other kit comes with the test results of specimens have been found. And for the phenomenon is to study the problem. Materials and Methods: Estraiol test were referred to our hospital which results of samples as more than 100pg/ml 75 specimens measured by radioimmunoassay(RIA) test with company A company B company C company D Kit, Chemiluminescent assay (CMIA) to examine and compare to the results from april to August in 2010. Results: Kit for each manufacturing company as measured by the results obtained using the average value of the correlation coefficient (R2) and A company 0.8906 B 0.9527 C 0.9547 and D company correlation coefficient of 0.873 showed a good correlation that measuring the results of A company high concentrations when Company B Company C Company D with CMIA test concentrations measured low results that the two cases were discovered specimens. Conclusion: Most of the test results of 75 samples came up with a similar trend, but two cases were reported in the patients very differently. A company result reported higher than 700 pg/ml, while the rest of other test results report was approximately 10 pg/ml. The common point of two samples more than 50 years patients are estimated to be diagnosed with cancer in postmenopausal patients receiving treatment and levels of FSH were found to be greater than 50 mIU/ml. Did not identify the exact cause. I suggest if you are using A company kit that need to again check when Estradiol result and follicle stimulating hormone results is higher.
This study was initiated to investigate the skin whitening activities of methanol extracts from fruiting bodies of I. obliquus. The total polyphenols and flavonoids contents of I. obliquus methanol extracts were 31.85 mg/g and 28.33 mg/g, respectively. The methanol extract of the mushroom treated on B16/F10 melanoma and NIH3T3 cell lines did not show cytotoxic activity. 2,2-diphenyl-1-picrylhydrazyl(DPPH) free radical scavenging activity and chelating activity on ferrous ions of I. obliquus methanol extract were lower than those of positive control, tocopherol and BHT. The tyrosinase and L-DOPA inhibitory activities of the extract were lower than those of positive control, kojic acid and ascorbic acid. The tyrosinase and melanin synthesis inhibitory activities of the melanoma cells treated with the extract were comparable with positive control, arbutin. The experimental results suggested that methanol extract of I. obliquus contained inhibitory activities of tyrosinase and melanin synthesis in the B16/F10 melanoma cells by dose dependent manner. High ultra-violet absorption spectra in the range of 280-350 nm showed that I. obliquus extract could protect skin from UV radiation damage. Therefore, fruiting bodies of I. obliquus can be used for developing skin whitening, anti-UV and skin care agents.
Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.
Liver regeneration is a result of highly coordinated proliferation of hepatocytes and nonparenchymal liver cells. Partial hepatectomy (PH) is the most often used stimulus to study liver regeneration because, compared with other methods that use hepatic toxins, it is not associated with the tissue injury and inflammation, and the initiation of the regenerative stimulus is precisely defined. Granulocyte macrophage-colony stimulating factor (GM-CSF), which is a cytokine able to regulate the proliferation and differentiation of epithelial cells, was first identified as the most potent mitogen for bone marrow. Particularly, rrhGM-CSF, which is highly glycosylated and sustained longer than any other types of GM-CSF in the blood circulation, was specifically produced from rice cell culture. In this experiment, effects of rrhGM-CSF administration were evaluated in the regenerating liver after 78% PH of rats. Morphological changes induced by PH were characterized by destroyed hepatocyte plate around the central vein and enlarged nuclear cytoplasmic ratio and increased hepatocytes with two nuclei. And then, proliferation of liver cells (parenchymal and nonparenchymal) and rearrangement of plates and lobules seemed to be carried out during liver regeneration. These alterations in the experimental group preceded those of the control. Since proliferating cell nuclear antigen (PCNA) is known to be a nuclear protein maximally elevated in the S phase of proliferating cells, the protein was used as a marker of liver regeneration after PH in rats. PCNA levels by western blot analysis and immunohistology were compared between the two groups. PCNA protein expression of two groups at 12 hr and 24 hr after injury showed similar pattern. The protein expression showed the peak at 3 days in both groups, however, the protein level of the experimental group was higher than that of the control. On immunohistochemical observations, the reaction product of PCNA was localized at the nuclei of proliferating cells and the positive reaction in experimental group at 3 days was clearly stronger than that in control group. The results by Western blotting and immunohistology for PCNA showed similar pattern in terms of the protein levels. In conclusion, rrhGM-CSF administration during liver regeneration after 78% PH accelerated breakdown and restoration of the hepatic plate and expression of PCNA. These results suggest that rrhGM-CSF might play an important role during liver regeneration in rats.
Fischer 344 rats aged six weeks were diYided into four groups and group 1, 2, and 3 of rats were given an intraperitoneal injection of diethylnitrosamine at 200 mg/kg body weight and group 4 was given saline alone. Two weeks after beginning of the experiment, group 1 and 2 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for four weeks. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. During the last two weeks, group 1 and 3 of rats were received subcutaneously 3 consecutive weekly doses of iron dextran at 0.125 ml/100 g body weight. Subcutaneous injection of iron dextran resulted in hepatic siderosis in group 1 and 3 of rats. Pre neoplastic nodules were identified histopathologically by two markers, resistance to exogenous iron accumulation and glutathione S-transeferase placental form (GST-P) activity, while early carcinogen induced foci were hardly resistant to iron accumulation and though a few lesions were identified, it could hardly be distincted from normal hepatocytes of surroundings. However, GST-P positive nodules as well as foci were clearly distincted from normal hepatic cells of surroundings. In the quantitative analysis of carcinogen-induced nodules and foci, more lesions were detected by immunohistochemical method for GST-P than by prussian blue staining for resistant to iron accumulation. It is concluded that immunohistochemical marker for GST-P is more sensitive and reliable than iron-resistance marker, and that iron-resistance is not useful marker for early detection of carcinogen-induced hepatic lesions.
Kim, Do-Soon;Park, Jueng-Eun;Seo, Kwon-Il;Ko, Sung-Ryong;Lee, Jong-Won;Do, Jae-Ho;Yee, Sung-Tae
Journal of Ginseng Research
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v.30
no.3
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pp.117-127
/
2006
Ginseng is a medicinal herb widely used in Asian countries. Dendritic cells(DCs) play a pivotal role in the initiation of T cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. In this study, we examined the effects of Red-ginseng(water extract, edible and fermented ethyl alcohol extract, crude saponin) on the DCs phenotypic and functional maturation. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated by water extract, edible and fermented ethyl alcohol extract, crude saponin and LPS, respectively, for 24hours. The expression of surface co-stimulatory molecules, including MHC(major histocompatibility complex) class II, CD40, CD80 and CD86, was increased on DCs that were stimulated with crude saponin, but antigen-uptake capacity was decreased. The antigen-presenting capacity of Red-ginseng extracts-treated DCs as analyzed by allogeneic T cells proliferation and IL-2, $IFN-{\gamma}$ production was increased. Furthermore, $CD4^+$ and $CD8^+$ syngeneic T cell(OVA-specific) proliferation and $IFN-{\gamma}$ production was significantly increased. However, $CD4^+$ syngeneic T cell secreted higher levels of IL-2 in responding but not $CD8^+$ syngeneic T cell. These results indicate the immunomodulatory properties of Red-ginseng extracts, which might be therapeutically useful in the control of cancers and immunodeficient diseases through the up-regulation of DCs maturation.
Choi, Eun Ok;Kwon, Da Hye;Kim, Min Young;Hwang-Bo, Hyun;Kim, Hong Jae;Ahn, Kyu Im;Jeong, Jin-Woo;Lee, Ki Won;Kim, Ki Young;Kim, Sung Goo;Choi, Young Whan;Hong, Su Hyun;Park, Cheol;Choi, Yung Hyun
Journal of Life Science
/
v.26
no.10
/
pp.1207-1213
/
2016
Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.
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