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Purpose@#To investigate the effects of latanoprostene bunod (LBN) on nitric oxide (NO) production and permeability in human trabecular meshwork cells (HTMC). @*Methods@#HTMC were treated with 50 and 100 µM LBN and latanoprost free acid (LAT) for 30 minutes. Additionally, 100 µM LBN was co-exposed to 0.5 mM L-NAME (N-Nitroarginine methyl ester). Cellular viability and NO production were measured using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) and Griess assays. The permeability and resistance of the HTMC monolayer were evaluated by trans-endothelial electrical resistance (TEER) and carboxyfluorescein permeability. @*Results@#Exposure to 100 µM LBN led to increased NO production, whereas co-exposure to L-NAME reduced NO production. Treatment with 100 µM LBN decreased the TEER of the HTMC monolayer. LBN exposure heightened carboxyfluorescein permeability, but co-exposure to 100 µM LBN and L-NAME reduced permeability. LAT treatment did not affect NO production or permeability. @*Conclusions@#LBN increased the permeability of the HTMC monolayer and increased NO production. Therefore, LBN might increase trabecular outflow in addition to promoting uveoscleral outflow.
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Purpose@#In retinal endothelial cells, homocysteine (Hcy) activates matrix metalloproteinase (MMP)-9, which results in apoptosis. This study investigated these effects of Hcy in human trabecular meshwork cells (HTMC). @*Methods@#HTMC cultures using 5 mM low or 20 mM high glucose (HG)-containing media were exposed to 100 μM Hcy for 3 days. Cell viability was assessed with the MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. The MMP-9 and tissue inhibitor of MMP (TIMP)-1 levels were measured by western blotting and the degree of apoptosis was analyzed with flow cytometry using Annexin-propidium iodide double staining. @*Results@#Exposure to Hcy in HG decreased cell viability compared to HG alone (p = 0.036). Compared to HG alone, co-exposure to Hcy with HG decreased the TIMP-1 levels, albeit not significantly (p = 0.094), and did not affect the MMP-9 levels (p = 0.413). In addition, co-exposure to Hcy with HG produced no difference in the degree of apoptosis compared to HG alone (p = 0.437). @*Conclusions@#Unlike in retinal endothelial cells, Hcy did not affect the activities of TIMP-1, MMP-9, or the degrees of apoptosis significantly in HTMC. Thus, the effects Hcy may be limited in HTMC.
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Objective@#To analyze the overall treatment effects in terms of the amount of uprighting with changes in the three-dimensional positions of the mandibular posterior teeth after applying the biocreative reverse curve (BRC) system. @*Methods@#Thirty-four patients (mean age, 20.5 ± 8.56 years) were treated using the BRC system (mean period, 8.17 ± 2.19 months). Cone-beam computed tomography was performed before treatment and after treatment with the BRC system. The three-dimensional movement of each tooth was analyzed in the coordinate system at points on the crown and root apex. A paired t-test was used to analyze the treatment effects of the BRC system. @*Results@#The application of the BRC system spanning from the first premolar to the second molar resulted not only in buccal and distal uprighting, but also in increased buccal and distal tipping of the teeth. The premolars and the first molar were extruded, and the second molar was intruded. @*Conclusions@#When the BRC system is applied, simultaneous distal and buccal uprighting of the premolars and molars can be achieved bilaterally using a temporary skeletal anchorage device without unnecessary movement of the anterior teeth.
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Purpose@#To investigate the effect of a prostaglandin (PG) analogue with or without preservative benzalkonium chloride (BAK) on corneal sensitivity. @*Methods@#Central corneal sensitivity was measured prospectively with a Cochet–Bonnet esthesiometer in patients with normal tension glaucoma (NTG) or primary open angle glaucoma (POAG) before and 1 and 3 months after treatment. All patients began treatment with PG monotherapy with or without BAK preservative. @*Results@#The study enrolled 84 patients: 52 NTG and 32 POAG. The treatment was PG with BAK preservative in 45 eyes and without BAK preservative in 39 eyes. Without BAK, the mean corneal sensitivity was 58.22 ± 3.56, 57.77 ± 4.59, and 56.33 ± 5.47 mm before and after 1 and 3 months, respectively; with BAK the mean corneal sensitivity was 58.20 ± 4.51, 56.31 ± 6.22, and 55.52 ± 6.23 mm. Corneal sensitivity was reduced significantly in patients using PG with the preservative BAK after 3 months (p = 0.033). Co-administration of artificial tears did not affect this reduction in corneal sensitivity. @*Conclusions@#PG with the preservative BAK reduced corneal sensitivity and artificial tears did not improve this reduction. Reduced corneal sensitivity and accompanying side effects should be considered in the long-term use of PG with the preservative BAK.
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Purpose@#Since the division of the Korean Peninsula into South and North Korea in 1948, the gaps in the medical system and the socioeconomic status between these 2 countries has expanded. The purpose of this study was to analyze the distribution of different areas of research, as well as the types of research that was conducted in the North Korean medical journal, ‘Pediatrics, Obstetrics and Gynecology.’ This study aimed to specifically investigate the medical research status of healthcare in women and children. @*Methods@#This study analyzed a total of 949 papers that were published in the North Korean medical journal, ‘Pediatrics, Obstetrics and Gynecology.’ Papers from January 2015 to December 2019 were included. For the analysis, the 8th Korean Standard Classification of Diseases, disease name, subspecialty classification, and research classifications were extracted from the papers.Result: Of the 949 papers included in the analysis, 495, 366, and 88 studies were conducted in the major fields of obstetrics and gynecology, pediatrics, and on breast surgery, respectively. Within the field of obstetrics and gynecology, the most studied subspecialties were maternal and fetal medicine, general gynecology, and gynecologic oncology. To a lesser extent, the following subspecialties were reported: gynecologic endocrinology (6.7%), infertility (6.3%), and urogynecology (approximately 1%). @*Conclusion@#Although North Korean papers differ from those published worldwide (due to government intervention), they are still a useful source of information as they are easier to access than alternative data sources. The results from this study have implications for understanding the distribution of research on different areas of healthcare, as well as the burden of healthcare in North Korea.
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Purpose@#To investigate the effects of prostaglandin E2 agonist omidenepag (OMD) on the expression of matrix metalloproteinase (MMP) in human trabecular meshwork (TM) cells. @*Methods@#Primarily cultured human TM cells were exposed to 0, 1, 10, or 40 µmol/L OMD for 3 days. The permeability through the TM cell monolayer was assessed using carboxyfluorescein. Expressions of messenger ribonucleic acid and protein levels of MMP-1, MMP-3, and MMP-9 were measured by reverse transcription polymerase chain reaction and Western blotting, respectively. Also, the permeability, expression of messenger ribonucleic acid, and protein levels of MMPs were measured after exposure to 1 µmol/L latanoprost free acid (LAT). @*Results@#OMD and LAT did not affect the cellular survival (all p > 0.05). Each concentration of OMD and LAT did not affect the permeability of carboxyfluorescein significantly (all p > 0.05). LAT increased the level of MMP-1 protein but did not increase the levels of MMP-3 and MMP-9 proteins. Each concentration of OMD did not affect the levels of MMP-1, MMP-3, and MMP9 proteins (all p > 0.05) @*Conclusions@#In TM cells, prostaglandin E2 agonist OMD did not increase the permeability through the TM cell monolayer, and the protein levels of MMPs. These suggest that the direct effect on the trabecular outflow by OMD may be limited.
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Purpose@#To investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) on the activity of matrix metalloproteinase (MMP) in human trabecular meshwork cells (HTMC). @*Methods@#Primary HTMC cultures were exposed to 0, 0.25, and 0.50 mg/mL anti-VEGF bevacizumab (BV) for 24 hours. The permeability through the trabecular meshwork cell monolayer was assessed using carboxyfluorescein and trans-epithelial endothelial electrical resistance (TEER). The levels of MMP-1/-2 were measured by Western blotting and the production of nitric oxide (NO) was assessed with the Griess assay. @*Results@#Bevacizumab at 0.50 mg/mL decreased the permeability of carboxyfluorescein significantly (p = 0.017) and did not affect TEER (p = 0.308). Administration of 0.50 mg/mL BV decreased MMP-1 and MMP-2 activities (p = 0.014, p = 0.016, respectively) and inhibited NO production significantly (p = 0.023). @*Conclusions@#Anti-VEGF decreased the permeability through the HTMC monolayer, which was accompanied by decreased MMP-1/-2 activity and limited NO production.
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Objective@#Triage in the emergency department is important as mistriage leads to inefficient use of resources. The Korean Triage and Acuity Scale (KTAS) was developed in 2012 and has been implemented in emergency departments nationwide since January 2016. The purpose of this study was to determine whether KTAS can predict resource use in a pediatric emergency center. @*Methods@#From October to December 2019, a retrospective analysis was conducted by a review of medical records. Demographic data, KTAS grades, Emergency Severity Index (ESI) as an indicator of resource utilization and details of the use of each resource were collected. Patients were divided into non-trauma and trauma groups. KTAS grades 1 and 2 were defined as the severe group, grade 3 was the moderate group, and grades 4 and 5 were defined as the mild group. We investigated whether triage using KTAS is related to resource utilization. @*Results@#In the non-trauma group, ESI, length of stay in the emergency department, and hospitalization were significantly correlated with the KTAS groups. In the trauma group, there was no significant difference between the moderate and mild groups in the above variables except for hospitalization. This was because there was no significant difference in sedation, procedure, and intravenous injection, in the trauma group. @*Conclusion@#The KTAS triage helped predict resource utilization in the non-trauma group, but not in the trauma group especially between the moderate and mild groups. Additional research will be needed to predict resource utilization in children with trauma.
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Purpose@#To investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) on the activity of matrix metalloproteinase (MMP) in human trabecular meshwork cells (HTMC). @*Methods@#Primary HTMC cultures were exposed to 0, 0.25, and 0.50 mg/mL anti-VEGF bevacizumab (BV) for 24 hours. The permeability through the trabecular meshwork cell monolayer was assessed using carboxyfluorescein and trans-epithelial endothelial electrical resistance (TEER). The levels of MMP-1/-2 were measured by Western blotting and the production of nitric oxide (NO) was assessed with the Griess assay. @*Results@#Bevacizumab at 0.50 mg/mL decreased the permeability of carboxyfluorescein significantly (p = 0.017) and did not affect TEER (p = 0.308). Administration of 0.50 mg/mL BV decreased MMP-1 and MMP-2 activities (p = 0.014, p = 0.016, respectively) and inhibited NO production significantly (p = 0.023). @*Conclusions@#Anti-VEGF decreased the permeability through the HTMC monolayer, which was accompanied by decreased MMP-1/-2 activity and limited NO production.
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Objective@#Triage in the emergency department is important as mistriage leads to inefficient use of resources. The Korean Triage and Acuity Scale (KTAS) was developed in 2012 and has been implemented in emergency departments nationwide since January 2016. The purpose of this study was to determine whether KTAS can predict resource use in a pediatric emergency center. @*Methods@#From October to December 2019, a retrospective analysis was conducted by a review of medical records. Demographic data, KTAS grades, Emergency Severity Index (ESI) as an indicator of resource utilization and details of the use of each resource were collected. Patients were divided into non-trauma and trauma groups. KTAS grades 1 and 2 were defined as the severe group, grade 3 was the moderate group, and grades 4 and 5 were defined as the mild group. We investigated whether triage using KTAS is related to resource utilization. @*Results@#In the non-trauma group, ESI, length of stay in the emergency department, and hospitalization were significantly correlated with the KTAS groups. In the trauma group, there was no significant difference between the moderate and mild groups in the above variables except for hospitalization. This was because there was no significant difference in sedation, procedure, and intravenous injection, in the trauma group. @*Conclusion@#The KTAS triage helped predict resource utilization in the non-trauma group, but not in the trauma group especially between the moderate and mild groups. Additional research will be needed to predict resource utilization in children with trauma.
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Objective@#Although accurate diagnosis in neurologic emergencies is critical, the emergency department (ED) suffers from a shortage of neurologists. The purpose of this study was to investigate the effect of a dedicated neurologist on the competence in the management of ED physicians on patients with neurologic abnormalities. @*Methods@#We retrospectively reviewed the medical records of patients with neurologic abnormalities between 1 March 2016 and 30 September 2019. Two periods, including control and intervention periods, were assigned. Neurology consultations were routinely performed by an ED physician in the control period and by a physician of the ED working with a dedicated neurologist in the intervention period. @*Results@#In the control period, the most frequent chief complaints were dizziness (22.45%), focal motor weakness (except the face, 19.62%), altered mental status (9.98%), dysarthria (9.62%), seizures (8.57%), and headaches (6.87%). In the intervention period, the rate of final disposition by the ED physician was significantly increased in patients with dizziness (P<0.001), altered mental status (P=0.003), dysarthria (P<0.001), seizure (P<0.001), headaches (P<0.001), facial palsy (P<0.001), and memory impairment (P=0.043). @*Conclusion@#ED physicians who were educated by a dedicated neurologist could effectively enhance the competence in the management of the patient with neurologic abnormalities. We suggest that the method implemented in this study can be a good alternative for solving the gap in neurology department consultation.
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PURPOSE: To investigate the effects of hydrogen sulfide (H₂S) on the permeability of a cultured human trabecular meshwork cells (HTMC) monolayer and its interaction with nitric oxide (NO).METHODS: After exposing primary cultured HTMCs to 0, 50, 100, and 500 µM sodium hydrogen sulfide (NaHS) for 6 hours, the permeabilities through the HTMC monolayer were measured using a Transwell assay with carboxyfluorescein. The production of NO and eNOS mRNA expression were assessed using the Griess assay and reverse transcription-polymerase chain reaction, respectively. In addition, 0, 1, and 10 µM NaHS and 10 µM sodium nitroprusside (SN) were co-exposed to evaluate the possible synergistic effect of H₂S and NO.RESULTS: Greater than 100 µM NaHS increased the permeability through the HTMC monolayer in a dose-dependent manner (p < 0.05). These increased permeabilities were not accompanied by NO production or eNOS mRNA expression (p > 0.05). When 0, 1, and 10 µM NaHS and 10 µM SN were exposed together, there was no significant change of permeability, NO production, or eNOS mRNA expression (all, p > 0.05).CONCLUSIONS: NaHS at high concentrations increased the permeability of the HTMC monolayer, which was not affected by NO. NaHS at low concentrations did not show a synergistic effect with NO. Thus, H₂S at high concentrations may increase trabecular outflow, which may not be associated with NO.
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Purpose@#To investigate the effects of hydrogen sulfide (H2S) on the senescence and oxidative stress of cultured human trabecularmeshwork cells (HTMCs). @*Methods@#After inducing oxidative stress with 200 μM hydrogen peroxide (H2O2), primary cultured HTMCs were exposed to 0, 50,and 100 μM sodium hydrogen sulfide (NaHS) for 24 hours. Cell survival and senescence were measured using an MTT assayand SA-β-galactosidase staining, respectively. Generation of reactive oxygen species (ROS) and superoxide were measuredusing the dichlorofluorescein assay and modified cytochrome c assay. Production of nitric oxide (NO) and expression of eNOSmRNA were assessed using the Griess assay and reverse polymerase chain reaction. @*Results@#Cell survival was not affected by 200 μM H2O2. Exposure to 50 and 100 μM NaHS significantly decreased cellular senescence,compared with the H2O2-exposed control. Exposure to 50 and 100 μM NaHS decreased the generation of ROS, andexposure to 100 μM NaHS decreased the generation of superoxide. Treatment with 100 μM NaHS increased the production ofNO and expression of eNOS mRNA, respectively. @*Conclusions@#NaHS decreased the cellular senescence associated with the decreased generation of free radicals. Thus, H2Scould inhibit the senescence of HTMCs by reducing oxidative stress.
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Purpose@#We evaluated the protective effect of trabecular outflow drugs, Rho kinase (ROCK) inhibitors against oxidative stressin trabecular meshwork cells. @*Methods@#Primary-cultured human trabecular meshwork cells (HTMCs) were exposed to ROCK inhibitors at 10 and 20 μMY-27632, ripasudil or fasudil for 24 hours, after pretreatment with 200 μM hydrogen peroxide for 30 min. The cell viabilities andmetabolic activities were assessed using the Trypan Blue dye exclusion test and MTT assay, respectively. Reactive oxygen species(ROS) production was measured using the H2DCFDA assay, and the degree of apoptosis was measured with flow cytometryusing annexin-propidium iodide double staining. @*Results@#In HTMCs, Y-27632 suppressed ROS production. Ripasudil and fasudil increased the metabolic activities and decreasedthe degrees of apoptosis. Fasudil showed the most cytoprotective effects among the three ROCK inhibitors tested. @*Conclusions@#Against oxidative stress, ROCK inhibitors decreased apoptosis accompanied by decreased ROS production, especiallyfasudil. ROCK inhibitors may therefore have cytoprotective properties in addition to increasing trabecular outflow.
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Purpose@#To investigate the pathway and effects of minoxidil on trabecular outflow in cultured human trabecular meshwork (TM) cells. @*Methods@#After exposing primarily cultured TM cells to 0, 10, 50, or 100 µM minoxidil sulfate (MS), trabecular outflow was assessed by measuring TM cell monolayer permeability to carboxyfluorescein and transepithelial electrical resistance. To assess the pathway of permeability changes, caveolin-1, occludin, and claudin-5 levels were measured via western blot. Generation of reactive oxygen species (ROS) was measured using the dichlorofluorescein diacetate assay. To assess the involvement of nitric oxide (NO) in minoxidil-induced permeability increase, the degrees of endothelial nitric oxide synthase mRNA expression and NO production were measured with reverse transcription polymerase chain reaction and Griess assays, respectively. Permeability was also measured with co-exposure to 50 µM N-acetyl cysteine. @*Results@#MS significantly increased TM cell monolayer permeability (p < 0.05) and decreased transepithelial electrical resistance (p < 0.05). MS decreased the degree of endothelial nitric oxide synthase mRNA expression but did not affect NO production. MS decreased occludin and claudin-5 levels but did not affect caveolin-1 level. MS at 100 µM increased the generation of ROS, and MS-induced permeability increase was attenuated after co-exposure to 50 µM N-acetyl cysteine. @*Conclusions@#Minoxidil may preferentially increase trabecular permeability via a paracellular pathway by downregulation of tight junction proteins. This minoxidil-induced permeability through the TM may be mediated by generation of ROS.
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Background@#and Purpose: The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) is widely used for estimating the symptoms of Parkinson’s disease. Translation and validation of the MDS-UPDRS is necessary for non-English speaking countries and regions. The aim of this study was to validate the Korean version of the MDS-UPDRS. @*Methods@#Altogether, 362 patients in 19 centers were recruited for this study. We translated the MDS-UPDRS to Korean using the translation-back translation method and cognitive pretesting. We performed both confirmatory and exploratory factor analyses to validate the scale.We calculated the comparative fit index (CFI) for confirmatory factor analysis, and used unweighted least squares for exploratory factor analysis. @*Results@#The CFI was higher than 0.90 for all parts of the scale. Exploratory factor analysis also showed that the Korean MDS-UPDRS has the same number of factors in each part as the English version. @*Conclusions@#The Korean MDS-UPDRS has the same overall structure as the English MDSUPDRS. Our translated scale can be designated as the official Korean MDS-UPDRS.
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PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.
Subject(s)
Humans , Adenosine , Blotting, Western , Cyclic GMP , Dipyridamole , Matrix Metalloproteinases , Nitric Oxide , Permeability , Phosphodiesterase Inhibitors , Theophylline , Trabecular MeshworkABSTRACT
PURPOSE: To investigate the role of hydrogen sulfide in the survival and collagen gel contraction of cultured human Tenon's capsule fibroblasts (HTCFs). METHODS: Primarily cultured HTCFs were exposed to 0, 100, 200, or 300 µM hydrogen sulfide (sodium hydrogen sulfide, NaHS) for 2 days. Cellular survival was assessed by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Degree of apoptosis was assessed with flow cytometry using annexin-V/propidium iodide double staining. To evaluate the effect of NaHS on cellular transdifferentiation, HTCFs were stimulated with 5 ng/mL TGF-β1 and the level of expression of α-smooth muscle actin (SMA) mRNA was assessed using reverse-transcription polymerase chain reaction. The cells were embedded in collagen gel, and the amount of gel contraction was measured. RESULTS: NaHS at 300 µM reduced HTCF survival (p = 0.013); NaHS at both 200 and 300 µM increased apoptosis in a dose-dependent manner (p = 0.013 and p = 0.016). TGF-β1 increased the expression of α-SMA mRNA (p = 0.041); co-treatment with 100 µM NaHS decreased TGF-β1-induced α-SMA mRNA expression (p = 0.039) and inhibited collagen gel contraction. CONCLUSIONS: NaHS at high concentration reduced cellular survival and increased HTCF apoptosis. NaHS decreased TGF-β 1-induced increases in α-SMA mRNA expression and collagen gel contraction. Thus, hydrogen sulfide may suppress scar formation by inhibiting HTCF transdifferentiation and contraction of collagen gels.
Subject(s)
Humans , Actins , Apoptosis , Cicatrix , Collagen , Fibroblasts , Flow Cytometry , Gels , Hydrogen Sulfide , Hydrogen , Polymerase Chain Reaction , RNA, Messenger , Tenon CapsuleABSTRACT
PURPOSE: We investigated the extent of adenosine A1 agonist-induced expression and regulation of matrix metalloproteinase 2 (MMP-2) synthesis in human trabecular meshwork cells (HTMC). METHODS: Primary HTMC cultures were exposed to 0.1 or 1.0 µM N6-cyclohexyladenosine (CHA) for 2 h in the presence or absence of an inhibitor thereof, 8-cyclopentyl-1,3-dimethylxanthine (CPT). The expression level of mRNA encoding MMP-2 was assessed via reverse transcription-polymerase chain reaction, and the levels of tissue inhibitor of metalloproteinase 2 (TIMP2) and membrane-type-1 MMP (MT1-MMP) measured by Western blotting. The permeability of the HTMC monolayer was assessed with the aid of carboxyfluorescein. RESULTS: CHA at 1.0 µM increased the permeability of the HTMC monolayer (p = 0.003) and CHA at both 0.1 and 1.0 µM significantly increased MMP-2 mRNA expression, which was inhibited by co-exposure to CPT (all p < 0.05). CHA increased MMP-2 activity, decreased that of TIMP2, and increased that of MT1-MMP (all p < 0.05). CONCLUSIONS: CHA increased the permeability of the HTMC monolayer and increased MMP-2 activity, decreased TIMP2 activity, and increased MT1-MMP activity. Thus, regulation of TIMP2 and MT1-MMP expression may be involved in the adenosine A1 agonist-induced increase in MMP-2 activity.
Subject(s)
Humans , Adenosine , Blotting, Western , Matrix Metalloproteinase 14 , Matrix Metalloproteinase 2 , Permeability , RNA, Messenger , Tissue Inhibitor of Metalloproteinase-2 , Trabecular MeshworkABSTRACT
PURPOSE: To investigate the effects of valproic acid on the survival of cultured human Tenon's capsule fibroblasts (HTFBs). METHODS: Primary cultured HTFBs were exposed to 0, 0.25, 0.5, and 1.0 mM valproic acid with or without 0, 1.0, 2.5 µg/mL mitomycin C, and incubated for 5 days. Cell survival was assessed using an MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and the degree of apoptosis was assessed by flow cytometry using annexin-V/propidium iodide double staining. RESULTS: Valproic acid decreased the survival of HTFBs in a dose-dependent manner, and survival was further decreased by adding mitomycin C to valproic acid. Both valproic acid and mitomycin C induced apoptosis of HTFBs. Valproic acid induced less apoptosis than mitomycin C. CONCLUSIONS: Valproic acid decreased the cellular survival of HTFBs and induced apoptosis. The antiproliferative effects of valproic acid were further enhanced by the addition of mitomycin C.