ABSTRACT
Purpose@#Early recurrence of hepatocellular carcinoma (HCC) remains a challenging issue after hepatic resection (HR) because of the associated poor prognosis. Models for tumor recurrence after liver transplantation (MoRAL) have been designed to predict tumor recurrence in HCC patients in the liver transplantation setting. This study aimed to validate the predictability of MoRAL for HCC recurrence or patient death and to evaluate the predictors of early HCC recurrence in hepatectomy patients with treatment-naïve solitary HCC. @*Methods@#This study included 443 patients with HCC recurrence after HR from January 2005 to December 2011. Patients were stratified into early recurrence (n = 312) and late recurrence (n = 131) groups according to the development of recurrence either within or more than 2 years after hepatectomy. @*Results@#The median levels of alpha-fetoprotein and protein induced by vitamin K absence-II and the median MoRAL score were significantly higher in the early recurrence group than in the late recurrence group. Regarding pathologic characteristics, the median tumor size, prevalence of tumor grade 3 or 4, microvascular invasion, presence of tumor necrosis, and macrovascular invasion in the early recurrence group were greater than those in the late recurrence group.Multivariate analysis showed that tumor grade 3 or 4, microvascular invasion, and high preoperative MoRAL score were predisposing factors for early HCC recurrence after HR. @*Conclusion@#The MoRAL score can be used to predict early recurrence in patients with HCC who undergo curative HR.Using this model, other treatments could be considered for patients with early recurrence predicted after HR.
ABSTRACT
Objectives@#This study aims to assess dental hygienists’ level of digital literacy and its effect on occupational self-efficacy and organizational commitment. @*Methods@#The online survey results, obtained from 307 respondents, were statistically analyzed using frequency analysis, t-test, one-way ANOVA, and multiple regression analysis with the IBM SPSS 20.0 software. @*Results@#The factors affecting the technology portion of digital literacy included age (P<0.001), years in career (P<0.001), number of personnel in workplace (P=0.009), level of education (P=0.001), region of workplace (P=0.002), and form of workplace (P=0.021). The factors affecting the application portion of digital literacy included age (P<0.001), years in career (P=0.009), and number of personnel in the workplace (P=0.008). The level of occupational self-efficacy positively affected the technology portion of digital literacy, while organizational commitment positively affected the technology portion and negatively affected the application portion of digital literacy. @*Conclusions@#Although this study has limitations, it carries significance as a survey of dental hygienists’ digital literacy standing. To adapt to and function in the current society of digital informatics, ongoing education and research on digital literacy are warranted.
ABSTRACT
Aging in mammals, including humans, is accompanied by loss of bone and muscular function and mass, characterized by osteoporosis and sarcopenia.Although resistance exercise training (RET) is considered an effective intervention, its effect is blunted in some elderly individuals. Fibroblast growth factor (FGF) and its receptor, FGFR, can modulate bone and muscle quality during aging and physical performance. To elucidate this possibility, the FGFR inhibitor NVP-BGJ398 was administrated to C57BL/6n mice for 8 weeks with or without RET. Treatment with NVPBGJ398 decreased grip strength, muscular endurance, running capacity and bone quality in the mice. FGFR inhibition elevated bone resorption and relevant gene expression, indicating altered bone formation and resorption. RET attenuated tibial bone resorption, accompanied by changes in the expression of relevant genes. However, RET did not overcome the detrimental effect of NVP-BGJ398 on muscular function. Taken together, these findings provide evidence that FGFR signaling may have a potential role in the maintenance of physical performance and quality of bone and muscles.
ABSTRACT
Purpose@#To report a case of unilateral progressive atypical acute zonal outer retinitis in a healthy young female.Case summary: A 32-year-old healthy woman presented with visual disturbance in the left eye for 1 week. Best corrected visual acuity was 0.4 in the left eye. No abnormal findings were detected on brain magnetic resonance imaging and a laboratory work-up. Zonal retinal opacity around the optic nerve disc was noticed in a fundus photo which was consistent with the outer retinal signal defect on optical coherence tomography and a defect in the central visual field from perimetry. Multiple evanescent white dot syndrome was suspected based on fluorescein angiography and indocyanine green angiography. Prednisolone was prescribed. Visual acuity was reduced to hand-motion after 10 days with extended zonal retinal opacity. No virus was detected by multiplex polymerase chain reaction of the aqueous humor. The lesion did not improve despite high-dose intravenous steroid and antiviral treatment. @*Conclusions@#Visual function was lost with the progression of outer retinitis. This case differed from previous cases as the outer retinitis progressed rapidly from the posterior pole to the peripheral retina. It was named fulminant progressive atypical acute zonal outer retinitis.
ABSTRACT
Purpose@#We report a case of infectious scleritis featuring kissing choroidal detachment and serous retinal detachment.Case summary: A 65-year-old female presented with ocular pain and hyperemia of the right eye 1 week in duration. Anterior chamber inflammation was evident. After pterygium excision, a thinned sclera and loss of conjunctiva around a necrotic lesion were observed. Necrotizing scleritis with anterior uveitis was diagnosed and topical and systemic steroids commenced. After 1 week, the scleral thickness increased, but conjunctival injection and choroidal detachment were newly noticed. Infectious scleritis was suspected and the pterygium excision site cultured. Although empirical antibiotics (fortified ceftazidime and tobramycin) were prescribed, the choroidal and serous retinal detachments became aggravated. Pseudomonas aeruginosa was identified on scleral culture, and topical piperacillin/tazobactam and systemic cefepime (2 g) commenced. Although the antibiotics were appropriate, the choroidal and serous retinal detachments became further aggravated. Necrotic tissue was subjected to surgical debridement. Two days later, the infectious signs had diminished and a systemic steroid was added. Over the next few weeks, all of the choroidal and serous retinal detachments, and the infectious signs, improved. @*Conclusions@#Patients with infectious scleritis featuring severe choroidal detachment and serous retinal detachment resistant to appropriate antibiotics may require surgical debridement of necrotic tissue. After controlling the infectious signs, systemic steroids should be considered to ensure a good prognosis.
ABSTRACT
Purpose@#To report a case of poor visual prognosis complicated by residual subretinal fluid after use of the internal limiting membrane flap technique to treat macular hole retinal detachment in a patient with high myopia.Case summary: A 55-year-old male stated that he had experienced a transparent circle in the central visual field of the right eye for 1 month. His best-corrected visual acuity (BCVA) was 0.32 and the axial length of the right eye was 32.57 mm. Fundus examination revealed a macular hole with retinal detachment localized to the posterior pole. We performed vitrectomy, membrane peeling, internal limiting membrane peeling with inverted internal limiting membrane flap, and silicone oil injection. On day 1 after surgery, the macular hole was closed, but subretinal fluid was noticed in the macula. At 3 months after surgery, the BCVA was 0.16 and the silicone oil was removed. At 14 months after the first surgery, the subretinal fluid was completely absorbed, but leopard-pattern pigment degeneration became prominent and the macula exhibited ellipsoid zone disruption. The BCVA decreased to 0.1. @*Conclusions@#In patients exhibiting macular hole retinal detachment in the context of high myopia, an inverted internal limiting membrane flap may increase the macular hole closure rate but disturb subretinal fluid drainage. As persistent subretinal fluid may cause permanent retinal damage with a poor visual prognosis, the surgical method must be carefully chosen.
ABSTRACT
Purpose@#To report a case of unilateral progressive atypical acute zonal outer retinitis in a healthy young female.Case summary: A 32-year-old healthy woman presented with visual disturbance in the left eye for 1 week. Best corrected visual acuity was 0.4 in the left eye. No abnormal findings were detected on brain magnetic resonance imaging and a laboratory work-up. Zonal retinal opacity around the optic nerve disc was noticed in a fundus photo which was consistent with the outer retinal signal defect on optical coherence tomography and a defect in the central visual field from perimetry. Multiple evanescent white dot syndrome was suspected based on fluorescein angiography and indocyanine green angiography. Prednisolone was prescribed. Visual acuity was reduced to hand-motion after 10 days with extended zonal retinal opacity. No virus was detected by multiplex polymerase chain reaction of the aqueous humor. The lesion did not improve despite high-dose intravenous steroid and antiviral treatment. @*Conclusions@#Visual function was lost with the progression of outer retinitis. This case differed from previous cases as the outer retinitis progressed rapidly from the posterior pole to the peripheral retina. It was named fulminant progressive atypical acute zonal outer retinitis.
ABSTRACT
Purpose@#We report a case of infectious scleritis featuring kissing choroidal detachment and serous retinal detachment.Case summary: A 65-year-old female presented with ocular pain and hyperemia of the right eye 1 week in duration. Anterior chamber inflammation was evident. After pterygium excision, a thinned sclera and loss of conjunctiva around a necrotic lesion were observed. Necrotizing scleritis with anterior uveitis was diagnosed and topical and systemic steroids commenced. After 1 week, the scleral thickness increased, but conjunctival injection and choroidal detachment were newly noticed. Infectious scleritis was suspected and the pterygium excision site cultured. Although empirical antibiotics (fortified ceftazidime and tobramycin) were prescribed, the choroidal and serous retinal detachments became aggravated. Pseudomonas aeruginosa was identified on scleral culture, and topical piperacillin/tazobactam and systemic cefepime (2 g) commenced. Although the antibiotics were appropriate, the choroidal and serous retinal detachments became further aggravated. Necrotic tissue was subjected to surgical debridement. Two days later, the infectious signs had diminished and a systemic steroid was added. Over the next few weeks, all of the choroidal and serous retinal detachments, and the infectious signs, improved. @*Conclusions@#Patients with infectious scleritis featuring severe choroidal detachment and serous retinal detachment resistant to appropriate antibiotics may require surgical debridement of necrotic tissue. After controlling the infectious signs, systemic steroids should be considered to ensure a good prognosis.
ABSTRACT
Purpose@#To evaluate the efficacy of trabeculectomy with mitomycin C (MMC) for primary open angle glaucoma (POAG) in eyes refractory to a trabecular micro-bypass stent. @*Methods@#We reviewed the medical records of patients with POAG who underwent trabeculectomy with MMC after failed trabecular micro-bypass stent implantation. All patients had a ≥12 months follow-up. We compared surgical outcomes according to trabecular micro-bypass stent implantation using a Kaplan-Meier survival analysis. Complete surgical success was defined as intraocular pressure (IOP) ≤18 mmHg and IOP reduction ≥20% without medication. @*Results@#A total of 19 patients (20 eyes) were included; 10 eyes of nine patients in the trabecular micro-bypass stent group and 10 eyes of 10 patients in the control group. The cumulative probabilities of complete success after trabeculectomy with MMC were 80% and 90% after 1 year in the trabecular micro-bypass stent and control groups, respectively (p = 0.584). Mean IOP decreased from 29.0 ± 7.4 mmHg preoperatively to 12.4 ± 3.1 mmHg at the final visit in the trabecular micro-bypass stent group (p < 0.001). Mean IOP decreased from 29.2 ± 7.5 mmHg preoperatively to 12.1 ± 4.1 mmHg at the final visit in the control group (p < 0.001). The preoperative and final IOP were not significantly different between the two groups (p = 0.828, p = 0.387, respectively). @*Conclusions@#Trabeculectomy with MMC was an effective method for controlling IOP in patients with POAG refractory to a trabecular micro-bypass stent.
ABSTRACT
Purpose@#To report a rare case of corneal perforation treated with a multilayer collagen sheet graft transplantation after amniotic membrane graft failure to prevent corneal perforation in a fungal corneal ulcer.Case summary: A 64-year-old woman with a past history of rheumatoid arthritis 1 year prior was transferred to our hospital due to unresponsive treatment of a corneal ulcer. Although the corneal ulcer of the right eye was treated with antibiotics for 10 days, loss of the corneal epithelial layer and corneal stromal infiltration were observed on examination. A culture test was conducted on the corneal ulcer that identified the pathogen as the Paecilomyces strain. Corneal perforation occurred 1 month after undergoing an amniotic membrane graft to prevent this outcome. A multilayer collagen sheet graft (Aongen®; Pharos Tech Medical, Seoul, Korea) was applied at the perforated corneal ulcer site without a donor cornea. One year after this operation, visual acuity has not been restored; however, corneal perforation of the ulcer site has not progressed. @*Conclusions@#If there is no donor cornea, partial corneal transplantation using a multilayer collagen sheet graft is thought to be a therapeutic method to treat corneal perforation in cases involving impacted corneal perforation or corneal perforation that occurs in corneal disease.
ABSTRACT
TWIK-related two-pore domain K+ channel-2 (TREK-2) has voltageindependent activity and shows additional activation by acidic intracellular pH (pH i ) via neutralizing the E332 in the cytoplasmic C terminal (Ct). We reported opposite regulations of TREK-2 by phosphatidylinositol 4,5-bisphosphate (PIP2 ) via the alkaline K330 and triple Arg residues (R355-357) inhibition and activation, respectively. The G334 between them appeared critical because its mutation (G334A) endowed hTREK-2 with tonic activity, similar to the mutation of the inhibitory K330 (K330 A). To further elucidate the role of putative bent conformation at G334 ,we compared the dual mutation forms, K330 A/G334 A and G334 A/R 355-7 A, showing higher and lower basal activity, respectively. The results suggested that the tonic activity of G334 A owes to a dominant influence from R355-7. Since there are additional triple Arg residues (R 377-9 ) distal to R355-7 , we also examined the triple mutant (G334A/R355-7 A/R377-9 A) that showed tonic inhibition same with G334 A/R 355-7 A. Despite the state of tonic inhibition, the activation by acidic pH i was preserved in both G 334 A/R355-7 A and G334 A/R 355-7A/R377-9 A, similar to the R355-7 A.Also, the inhibitory effect of ATP could be commonly demonstrated under the activation by acidic pH i in R355-7A, G334 A/R355-7 A, and G334 A/R355-7 A/R377-9 A. These results suggest that the putative bent conformation at G334 is important to set the tug-of-war between K330 and R355-7 in the PIP2 -dependent regulation of TREK-2.
ABSTRACT
KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.
ABSTRACT
TWIK-related two-pore domain K+ channel-2 (TREK-2) has voltageindependent activity and shows additional activation by acidic intracellular pH (pH i ) via neutralizing the E332 in the cytoplasmic C terminal (Ct). We reported opposite regulations of TREK-2 by phosphatidylinositol 4,5-bisphosphate (PIP2 ) via the alkaline K330 and triple Arg residues (R355-357) inhibition and activation, respectively. The G334 between them appeared critical because its mutation (G334A) endowed hTREK-2 with tonic activity, similar to the mutation of the inhibitory K330 (K330 A). To further elucidate the role of putative bent conformation at G334 ,we compared the dual mutation forms, K330 A/G334 A and G334 A/R 355-7 A, showing higher and lower basal activity, respectively. The results suggested that the tonic activity of G334 A owes to a dominant influence from R355-7. Since there are additional triple Arg residues (R 377-9 ) distal to R355-7 , we also examined the triple mutant (G334A/R355-7 A/R377-9 A) that showed tonic inhibition same with G334 A/R 355-7 A. Despite the state of tonic inhibition, the activation by acidic pH i was preserved in both G 334 A/R355-7 A and G334 A/R 355-7A/R377-9 A, similar to the R355-7 A.Also, the inhibitory effect of ATP could be commonly demonstrated under the activation by acidic pH i in R355-7A, G334 A/R355-7 A, and G334 A/R355-7 A/R377-9 A. These results suggest that the putative bent conformation at G334 is important to set the tug-of-war between K330 and R355-7 in the PIP2 -dependent regulation of TREK-2.
ABSTRACT
KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.
ABSTRACT
Purpose@#To report a rare case of corneal perforation treated with a multilayer collagen sheet graft transplantation after amniotic membrane graft failure to prevent corneal perforation in a fungal corneal ulcer.Case summary: A 64-year-old woman with a past history of rheumatoid arthritis 1 year prior was transferred to our hospital due to unresponsive treatment of a corneal ulcer. Although the corneal ulcer of the right eye was treated with antibiotics for 10 days, loss of the corneal epithelial layer and corneal stromal infiltration were observed on examination. A culture test was conducted on the corneal ulcer that identified the pathogen as the Paecilomyces strain. Corneal perforation occurred 1 month after undergoing an amniotic membrane graft to prevent this outcome. A multilayer collagen sheet graft (Aongen®; Pharos Tech Medical, Seoul, Korea) was applied at the perforated corneal ulcer site without a donor cornea. One year after this operation, visual acuity has not been restored; however, corneal perforation of the ulcer site has not progressed. @*Conclusions@#If there is no donor cornea, partial corneal transplantation using a multilayer collagen sheet graft is thought to be a therapeutic method to treat corneal perforation in cases involving impacted corneal perforation or corneal perforation that occurs in corneal disease.
ABSTRACT
In vascular smooth muscle, K⁺ channels, such as voltage-gated K⁺ channels (Kv), inward-rectifier K⁺ channels (Kir), and big-conductance Ca²⁺-activated K⁺ channels (BK(Ca)), establish a hyperpolarized membrane potential and counterbalance the depolarizing vasoactive stimuli. Additionally, Kir mediates endothelium-dependent hyperpolarization and the active hyperemia response in various vessels, including the coronary artery. Pulmonary arterial hypertension (PAH) induces right ventricular hypertrophy (RVH), thereby elevating the risk of ischemia and right heart failure. Here, using the whole-cell patch-clamp technique, we compared Kv and Kir current densities (I(Kv) and I(Kir)) in the left (LCSMCs), right (RCSMCs), and septal branches of coronary smooth muscle cells (SCSMCs) from control and monocrotaline (MCT)-induced PAH rats exhibiting RVH. In control rats, (1) I(Kv) was larger in RCSMCs than that in SCSMCs and LCSMCs, (2) I(Kv) inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMCs, (3) I(Kir) was smaller in SCSMCs than that in RCSMCs and LCSMCs, and (4) I(BKCa) did not differ between branches. Moreover, in PAH rats, I(Kir) and I(Kv) decreased in SCSMCs, but not in RCSMCs or LCSMCs, and I(BKCa) did not change in any of the branches. These results demonstrated that SCSMC-specific decreases in I(Kv) and I(Kir) occur in an MCT-induced PAH model, thereby offering insights into the potential pathophysiological implications of coronary blood flow regulation in right heart disease. Furthermore, the relatively smaller I(Kir) in SCSMCs suggested a less effective vasodilatory response in the septal region to the moderate increase in extracellular K⁺ concentration under increased activity of the myocardium.
Subject(s)
Animals , Rats , Coronary Vessels , Heart Diseases , Heart Failure , Hyperemia , Hypertension , Hypertrophy, Right Ventricular , Ischemia , Membrane Potentials , Monocrotaline , Muscle, Smooth , Muscle, Smooth, Vascular , Myocardium , Myocytes, Smooth Muscle , Patch-Clamp Techniques , Potassium Channels , Septum of BrainABSTRACT
PURPOSE: The purpose of this study was to compare the translucency and color changes of ceramic laminate veneers of different composition following glazing process. MATERIALS AND METHODS: 10 mm × 10 mm square specimens of 0.6 mm and 1.0 mm thicknesses were fabricated with IPS e.max Press (EM) and IPS e.max ZirPress (ZP) (n=10 per group). The color coordinates (CIE L* a* b*) of the specimens were recorded with a colorimeter before and after glazing. The color changes and translucency parameter (TP) were calculated. For the comparisons with the composition and thicknesses between the ‘not glazed’ and ‘glazed’ groups, statistical analyses were done through paired T-test, independent two-sample T-test, and multiple regression analysis using SPSS 18.0 (P < .05). RESULTS: The TP of 0.6 mm EM was higher than that of 0.6 mm ZP. Total color difference (ΔE*) between bare and glazed specimens of 1.0 mm EM was greater than that of 1.0 mm ZP with statistical significance. Following glazing, specimens from all groups showed statistically significant amount of decrease in L* and a*, and statistically significant increase in b*. The result of multiple regression analysis of EM and ZP showed that ΔL* improved ΔE*. CONCLUSION: Within the limitations of present study, we conclude that translucency and color of ceramic laminate veneers change significantly after glazing process, and the nature and amount of changes vary with different compositions.
Subject(s)
Ceramics , Dental VeneersABSTRACT
Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.
Subject(s)
Animals , Humans , Mice , Colitis , Colitis, Ulcerative , Colon , Cytokines , Dextran Sulfate , Dextrans , Epithelial Cells , Homeostasis , Inflammation , Inflammatory Bowel Diseases , Interferons , Interleukin-10 , Interleukin-17 , Interleukin-6 , Lymph Nodes , Peroxidase , Spleen , STAT3 Transcription Factor , T-LymphocytesABSTRACT
Myoblast fusion depends on mitochondrial integrity and intracellular Ca²⁺ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with [Ca²⁺]i regulation in normal and mitochondrial DNA-depleted (ρ0) L6 myoblasts. The ρ0 myoblasts showed impaired myotube formation. The inwardly rectifying K⁺ current (I(Kir)) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated Ca²⁺ channel and Ca²⁺-activated K⁺ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the I(Kir). The ρ0 myoblasts showed depolarized resting membrane potential and higher basal [Ca²⁺]ᵢ. Our results demonstrated the specific downregulation of I(Kir) by dysfunctional mitochondria. The resultant depolarization and altered Ca²⁺ signaling might be associated with impaired myoblast fusion in ρ0 myoblasts.
Subject(s)
Antimycin A , Down-Regulation , Electron Transport , Ion Channels , Membrane Potentials , Mitochondria , Muscle Development , Muscle Fibers, Skeletal , Myoblasts , Oxidative PhosphorylationABSTRACT
Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are anti-diabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by 1 µM gemigliptin while not by saxagliptin and sitagliptin up to 10 µM. The ACh-EDR of SHR MA was also improved by 1 µM gemigliptin while similar recovery was observed with higher concentration (10 µM) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endotheliumdenuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with 30 µM pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.