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1.
International Neurourology Journal ; : 285-295, 2021.
Article in English | WPRIM | ID: wpr-914698

ABSTRACT

Purpose@#Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injuries, their effects and mechanisms of action in bladder I/R injuries remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insults in rats. @*Methods@#One hundred male Sprague-Dawley rats were randomly divided into 5 groups, each of which contained 20 rats: a sham-operated group, a bladder I/R group, and bladder I/R groups treated with metformin, sildenafil, or both agents. Ischemia was induced by clamping the bilateral common iliac arteries with atraumatic vascular clamps for 2 hours, followed by reperfusion for 7 days. During this period, rats were injected once daily with 4-mg/kg metformin and/or 1-mg/kg sildenafil. @*Results@#I/R injuries induced increased malondialdehyde levels and myeloperoxidase activity and decreased superoxide dismutase activity. These changes were attenuated by treatment with metformin and/or sildenafil. The I/R group had significantly higher Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), Bax, caspase-3, and nuclear factor-kappa B (NF-κB) levels, and lower extracellular signal-regulated kinase, and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment. No differences in the levels of these markers were observed between rats coadministered metformin and sildenafil and those treated with either agent alone. @*Conclusions@#Metformin and sildenafil protected the rat bladder against I/R injuries. This effect may have been due to the inhibition of reactive oxygen species production through MAPK, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.

2.
Korean Circulation Journal ; : 482-489, 2006.
Article in English | WPRIM | ID: wpr-183603

ABSTRACT

BACKGROUND AND OBJECTIVES: Curcumin, a yellow pigment of turmeric in curry, has been reported to interfere with nuclear factor (NF)-kappaB. This study was designed to investigate the underlying pathway of the anti-inflammation effect of curcumin on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor (TNF)-alpha (10 ng/mL). The levels of intracellular reactive oxygen species (ROS) were examined using a fluorescent dye DCFH-DA, and the adhesion of U-937 monocytes to the HUVECs was then examined. Nuclear factor kappa B (NF-kappaB) activation was determined by the NF-kappaB p65 translocation to the nucleus via immunocytochemistry. The expression of the NF-kappaB dependent pro-inflammatory molecules were measured by RT-PCR and ELISA. The phosphorylations of c-Jun N-terminal protein kinase (JNK), p38 and STAT-3 (signal transducer and activator of transcription-3) were measured by Western blotting. RESULTS: Curcumin blocked the activation of NF-kappaB by TNF-alpha, and it also reduced the ROS, monocyte adhesion and the phosphorylation of JNK, p38 and STAT-3 in the TNF-alpha-stimulated HUVECs. The expression of intracellular cell adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8 were attenuated by curcumin at both the transcription and translation levels. CONCLUSION: We suggest that curcumin could contribute to protection against the adverse vascular effects of the pro-inflammatory response through the modulation of NF-kappaB, JNK, p38 and STAT-3, and this is in addition to its antioxidant effect in endothelial cells.


Subject(s)
Antioxidants , Blotting, Western , Cell Adhesion , Curcuma , Curcumin , Endothelial Cells , Enzyme-Linked Immunosorbent Assay , Human Umbilical Vein Endothelial Cells , Immunohistochemistry , Inflammation , Interleukins , JNK Mitogen-Activated Protein Kinases , Monocytes , Necrosis , NF-kappa B , Phosphorylation , Protein Kinases , Reactive Oxygen Species , Transducers , Tumor Necrosis Factor-alpha
3.
Korean Circulation Journal ; : 576-582, 2005.
Article in English | WPRIM | ID: wpr-189125

ABSTRACT

BACKGROUND AND OBJECTIVES: Carvedilol is an anti-oxidative, the cardioprotective effects of which are mediated by the inhibition of NF-kappaB activation. The present study was designed to examine the effects of carvedilol, an alpha1- and beta-blocker, on tumor necrosis factor (TNF)-alpha stimulated human umbilical vein endothelial cells (HUVEC). Materials and METHODS: HUVEC were treated with TNF-alpha (10 ng/mL) in either the absence or presence of carvedilol. The levels of intracellular reactive oxygen species (ROS) were examined using a fluorescent dye DCFH-DA, with the adhesion of U-937 monocyte to the HUVEC. Nuclear factor kappa B (NF-kappaB) activation was determined by NF-kappaB p65 translocation to the nucleus using Western blotting and immunocytochemistry. The expressions of NF-kappaB dependent pro-inflammatory molecules, i.e., vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, were measured by RT-PCR and ELISA. Bcl-2 and phosphorylation of c-Jun N-terminal protein kinase (JNK) were measured using Western blotting. RESULTS: TNF-alpha treatment increased the activation of NF-kappaB, suppressed Bcl-2, and increased the phosphorylation of JNK, the ROS level and the adhesion of U-937. The levels of mRNA and protein expressions of VCAM-1, ICAM-1, MCP-1 and IL-8 were up-regulated by TNF-alpha. Carvedilol inhibited the phosphorylation of JNK, ROS formation and the adhesion of U-937 monocyte. In addition, carvedilol reduced the production of VCAM-1, ICAM-1, MCP-1 and IL-8 at the mRNA and protein levels, via the suppression of NF-kappaB activation. CONCLUSION: These results suggested that the anti-inflammatory effects of carvedilol on TNF-alpha stimulated endothelial cells could be explained by its ROS-scavenging and NF-kappaB inactivation properties.


Subject(s)
Humans , Blotting, Western , Endothelial Cells , Enzyme-Linked Immunosorbent Assay , Human Umbilical Vein Endothelial Cells , Immunohistochemistry , Intercellular Adhesion Molecule-1 , Interleukin-8 , Interleukins , Monocytes , NF-kappa B , Phosphorylation , Protein Kinases , Reactive Oxygen Species , RNA, Messenger , Tumor Necrosis Factor-alpha , Vascular Cell Adhesion Molecule-1
4.
Journal of Veterinary Science ; : 131-137, 2004.
Article in English | WPRIM | ID: wpr-128641

ABSTRACT

Toxic effects of ozone, 4-(N-methyl-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK), and/or dibutyl phthalate (DBP) were examined through NF-kappaB, AP-1, Nrf2, and osteopontin (OPN) in lungs and livers of B6C3F1 mice. Electrophoretic mobility shift assay (EMSA) indicated that mice treated with combination of toxicants induced high NF-kappaB activities. Expression levels of p105, p65, and p50 proteins increased in all treated mice, whereas IkB activity was inhibited in NNK-, DBP-, and combination-treated ones. All treated mice except ozone-treated one showed high AP-1 binding activities. Expression levels of c-fos, c-jun, junB, jun D, Nrf2, and OPN proteins increased in all treated mice. Additive interactions were frequently noted from two-toxicant combination mice compared to ozone-treated one. These results indicate treatment of mixture of toxicants increased toxicity through NF-kappaB, AP-1, Nrf2, and OPN. Our data could be applied to the elucidation of mechanism as well as the risk assessment of mixture-induced toxicity.


Subject(s)
Animals , Mice , Blotting, Western , DNA-Binding Proteins/metabolism , Dibutyl Phthalate/toxicity , Electrophoretic Mobility Shift Assay , Kidney/drug effects , Liver/drug effects , Mice, Inbred Strains , NF-E2-Related Factor 2 , NF-kappa B/metabolism , Nitrosamines/toxicity , Osteopontin , Ozone/toxicity , Proto-Oncogene Proteins/metabolism , Risk Assessment , Sialoglycoproteins/metabolism , Trans-Activators/metabolism , Transcription Factor AP-1/metabolism
5.
Korean Journal of Perinatology ; : 135-140, 2002.
Article in Korean | WPRIM | ID: wpr-45938

ABSTRACT

OBJECTIVE: Mean weight gains, standard deviations were calculated for each gestational months and the 10th, 25th, 50th, 75th, and 90th percentiles were determined. And the influence of prepregnancy body mass index and/or parity on monthly weight gain was investigated. METHODS: We analyzed the monthly weight gain data from 876 women who had healthy sigleton term pregnancy in Han-il Hospital(Jul 2001-Jun 2002). Data were categorized in three groups according to the prepregnancy body mass index. RESULTS: The monthly weight gain table has been determined and 'Sigmoid(S) shaped' monthly weight gain curve was presented. Primipara and multipara have less weight gain than nullipara in the 5th and the 7th-11th months. Monthly weight gains adjusted for parity and age were significantly different among prepregnancy body mass index groups from the 4th month. CONCLUSIONS: More careful prenatal care according to the monthly weight gain-gestational month tables is needed to prevent a lot of complications which may be associated with abnormal weight gain during pregnancy.


Subject(s)
Female , Humans , Pregnancy , Body Mass Index , Parity , Prenatal Care , Weight Gain
6.
Korean Journal of Obstetrics and Gynecology ; : 938-945, 2001.
Article in Korean | WPRIM | ID: wpr-98023

ABSTRACT

OBJECTIVE: To explore the intracellular signal transduction pathways of IL-1beta and TNF-alpha in inducing matrix metalloproteinase-9 (MMP-9) in human myometrial smooth muscle cells. METHODS: We studied the expression of MMP-9 induced by cytokines (TNF-alpha and IL-1beta) with zymography. The influence of TNF-alpha and IL-1beta on the phosphorylation of Jun N-terminal kinase (JNK) and IkB were studied with immunoblotting for p-JNK and p-IkB. The intranuclear shifting of NF-kB and AP-1 after treatment with TNF-alpha and IL-1beta were evaluated by EMSA. RESULTS: TNF-alpha- and IL-1beta-induced MMP-9 expression was not suppressed by NF-kB inhibitor (CAPE), AP-1 inhibitor (curcumin) and PKC inhibitor (calphostin C) but was inhibited by tyrosine kinase inhibitor (genistein). After treatment of myometrial smooth muscle cells with TNF-alpha and IL-1beta, phosphorylation of JNK and phosphorylation of IkB with degradation of IkB were evidently observed. The intranuclear translocations of NF-kB and AP-1 were strongly enhanced after treatment with TNF-alpha and IL-1 beta as demonstrated in EMSA. CONCLUSION: In myometrial smooth muscle cells, MMP-9 is induced by TNF-alpha and IL-1beta through PKC activation and transcriptional activations of NF-kB and AP-1. Independent of PKC activation, the signaling of TNF-alpha and IL-1beta in the induction of MMP-9 seems to be transmitted by way of either NF-kB or AP-1 activation in myometrial smooth muscle cells.


Subject(s)
Female , Humans , Pregnancy , Cytokines , Immunoblotting , Interleukin-1beta , Matrix Metalloproteinase 9 , Muscle, Smooth , Myocytes, Smooth Muscle , NF-kappa B , Phosphorylation , Phosphotransferases , Pregnant Women , Protein-Tyrosine Kinases , Signal Transduction , Transcription Factor AP-1 , Tumor Necrosis Factor-alpha , Uterus
7.
Korean Circulation Journal ; : 645-654, 2001.
Article in Korean | WPRIM | ID: wpr-98864

ABSTRACT

BACKGROUND: Acute thrombotic occlusion after percutaneous coronary intervention (PCI) is a serious complication that provokes acute myocardial infarction, cardiac death or emergent bypass surgery. The role of fibrinogen, C-reactive protein (CRP) and lipoprotein (a) [Lp(a)] in the patients who developed acute thrombotic occlusion after PCI was investigated. METHODS: The patients with acute coronary syndrome who underwent PCI at Chonnam National University Hospital between Jan. 1999 and Jun. 2000 were divided into two groups according to the occurrence of acute thrombotic occlusion: patients with thrombotic occlusion after PCI (Group I; 62.3+/-8.8 years, M:F=19:8) and patients without thrombotic occlusion after PCI (Group II; 59.6+/-10.6 years, M:F=271:95). Clinical and angiographic characteristics, levels of fibrinogen, CRP and Lp(a) were compared between two groups. RESULTS: There were no significant differences in the level of fibrinogen between two groups. The patients with elevated CRP (>0.5mg/dL) were more common in Group I than those in Group II (88.9% vs. 42.3%, p=0.0001) and the value of CRP was higher in Group I than in Group II (4.97+/-5.18 mg/dL vs. 2.27+/-4.23 mg/dL, p=0.002). The patients with high Lp(a) (>30mg/dL) were more prevalent in Group I than those in Group II (44.4% vs 18.6%, p=0.001). There were no significant differences in the risk factors for coronary artery disease, except for diabetes mellitus (Group I : Group II, 40.7% : 16.9%, p=0.002). Thrombolysis in Myocardial Infarction (TIMI) flow of Group I was lower than in Group II (p=0.0001). Multiple regression analysis after the adjustment for age, sex and other cardiovascular risk factors, diabetes mellitus, low TIMI flow, high CRP and Lp(a) were independently associated with the occurrence of acute thrombotic occlusion (p=0.008, 0.0001, 0.031, 0.035, respectively). CONCLUSION:The elevated values of CRP and Lp(a), diabetes mellitus, and low TIMI flow are significant predictive factors for the acute thrombotic occlusion in patients with acute coronary syndrome after PCI.


Subject(s)
Humans , Acute Coronary Syndrome , C-Reactive Protein , Coronary Artery Disease , Death , Diabetes Mellitus , Fibrinogen , Lipoprotein(a) , Lipoproteins , Myocardial Infarction , Percutaneous Coronary Intervention , Risk Factors , Thrombosis
8.
Korean Journal of Otolaryngology - Head and Neck Surgery ; : 42-47, 1998.
Article in Korean | WPRIM | ID: wpr-643618

ABSTRACT

BACKGROUND AND OBJECTIVES: The kinds of offending allergens in our environment have changed in accordance with the changes wrought in the living environment. Thus, the study of offending allergens in allergic rhinitis is important. This study attempted to find out annual and seasonal distribution of offending allergens in patients of allergic rhinitis and to investigate the common offending allergens. MATERIALS AND METHODS: A series of allergic skin tests were performed for 3,159 allergic rhinitis patients from Jan. 1981 to Jun. 1990 at the allergic clinic, St.Benedict Hospital, Pusan, Korea, and the results were reviewed. The allergic study included 1) an allergic skin test, 2) a nasal smear for eosinophil. RESULTS: The following summary shows the results of this study: 1) The ratio between male and female of allergic rhinitis patients was 1.15:1 with the peak age being the teens and the twenties (60.6%). 2) The peak season of allergic rhinitis was winter (29.6%), followed by autumn, spring and summer. 3) The common offending allergens were dust and mites (35.9%), pollens (31.2%), epithelials (24.8%). 4) The most common offending allergen was D. farinae (52.5%), followed by D. pteronyssinus, cat fur, Alder pollens and Hazel pollens. 5) 29.6% of patients reacted positive to the skin tests for perennial types of allergens only and 5.2% of patients demonstrated pure pollinosis. CONCLUSION: The most common offending allergen was found to be the dust mite, and the most common pollen was from Alder trees. Perennial types of allergic rhinitis exceeded seasonal types in their occurence.


Subject(s)
Adolescent , Animals , Cats , Female , Humans , Male , Allergens , Alnus , Dust , Eosinophils , Korea , Mites , Pollen , Rhinitis , Rhinitis, Allergic, Seasonal , Seasons , Skin Tests , Trees
9.
Korean Journal of Anatomy ; : 351-360, 1997.
Article in Korean | WPRIM | ID: wpr-654968

ABSTRACT

The expression of c-fos and c-jun in the brain of the rat after capsaicin treatment was investigated by in situ hybridization, dot blot hybridization and immunocytochemical methods. Adult male Sprague-Dawley rats[200g] were used for this study. The first set of rats received a single subcutaneous injection of capsaicin[50mg/Kg] dissolved in 10% Tween-80 and 10% ethanol in saline. The rats were decapitated 1, 3, 5, 10, 24, 72 hours and 1 week after capsaicin treatment. The control set of rats were treated with saline instead of capsaicin. In situ hybridization and dot blot hybridization were carried out. O1igonucleotide probe complimentary to c-fos mRNA sequences were used for this study and labeling of oligonucleotides was accomplished using the DNA tailing kit. The expression of c-fos mRNA on the nucleus of neurons in in situ hybridization was observed throughout the brain, and was especially abundant in the olfactory cortex, nucleus of diagonal band of Broca, habenular nuclei, periaqueductal gray, parabrachial nucleus, entopeduncular nucleus, ventral posterolateral nucleus of the thalamus and cerebellum. Compared to the control rats, c-fos mRNA were increased 24 hours after capsaicin injection and gradually decreased after 72 hours, returning to the normal control level 1 week after capsaicin injection. c-fos mRNA was detected only 1 week after capsaicin injection in the various areas of the brain. The fos protein-like immunoreactivity was initially somewhat decreased at 24 hours, but increased at 72 hours and reactions was maximally observed at 1 week after capsaicin treatment. But Jun protein immunoreactivity was not increased, on the contrary, it was even decreased both in numbers of reactive cells and immunoreactivity 1 week after capsaicin injection. From the above results, c-fos gene expression was pronounced in the nucleus concerned with pain, olfaction and taste such as VPL nucleus of the thalamus, olfactory cortex and parabrachial nucleus, in the limbic system concerned with stress and emotion such as nucleus of diagonal band of Broca, periaqueductal gray and habenular nucleus, in the structure concerned with somatic motor function such as entopeduncular nucleus and cerebellum. Also, the c-fos gene was activated by the capsaicin early in the course of effects, then the fos protein increased as a results of c-fos activation. On the other hand, c-jun did not respond to capsaicin treatment early in the course, but Jun protein decreased late in the course of capsaicin effects.


Subject(s)
Adult , Animals , Humans , Male , Rats , Brain , Capsaicin , Cerebellum , DNA , Entopeduncular Nucleus , Ethanol , Genes, fos , Habenula , Hand , In Situ Hybridization , Injections, Subcutaneous , Limbic System , Neurons , Olfactory Pathways , Oligonucleotides , Periaqueductal Gray , Rats, Sprague-Dawley , RNA, Messenger , Septal Nuclei , Smell , Thalamus , Ventral Thalamic Nuclei
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