Mitochondrial ATP-sensitive K+channels play a role in cardioprotection by Na+-H+exchange inhibition against ischemia/reperfusion injury

AbstractOBJECTIVESThe possible role of the ATP-sensitive potassium (KATP) channel in cardioprotection by Na+-H+exchange (NHE) inhibition was examined.BACKGROUNDThe KATPchannel is suggested to be involved not only in ischemic preconditioning but also in some pharmacological cardioprotection.METHODSInfarction was induced by 30-min coronary occlusion in rabbit hearts in situ or by 30-min global ischemia in isolated hearts. Myocardial stunning was induced by five episodes of 5-min ischemia/5-min reperfusion in situ. In these models, the effects of NHE inhibitors (cariporide and ethylisopropyl-amiloride [EIPA]) and the changes caused by KATPchannel blockers were assessed. In another series of experiments, the effects of EIPA on mitochondrial KATP(mito-KATP) and sarcolemmal KATP(sarc-KATP) channels were examined in isolated cardiomyocytes.RESULTSCariporide (0.6 mg/kg) reduced infarct size in situ by 40%, and this effect was abolished by glibenclamide (0.3 mg/kg), a nonselective KATPchannel blocker. In vitro, 1 μM cariporide limited infarct size by 90%, and this effect was blocked by 5-hydroxydecanoate (5-HD), a mito-KATPchannel blocker but not by HMR1098, a sarc-KATPchannel blocker. Infarct size limitation by 1 μM EIPA was also prevented by 5-HD. Cariporide attenuated regional contractile dysfunction by stunning, and this protection was abolished by glibenclamide and 5-HD. Ethylisopropyl amiloride neither activated the mito-KATPchannel nor enhanced activation of this channel by diazoxide, a KATPchannel opener.CONCLUSIONSOpening of the mito-KATPchannel contributes to cardioprotection by NHE inhibition, though the interaction between NHE and this KATPchannel remains unclear

Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study

This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries

Incidence and Risk of Anti-Resorptive Agent-Related Osteonecrosis of the Jaw after Tooth Extraction: A Retrospective Study

Bone-modifying agents (BMA) such as bisphosphonates and denosumab are frequently used for the treatment of bone metastases, osteoporosis, and multiple myeloma. BMA may lead to anti-resorptive agent-related osteonecrosis of the jaw (ARONJ). This study aimed to clarify the risk factors for and probabilities of developing ARONJ after tooth extraction in patients undergoing BMA therapy. In this study, the records of 505 target sites of 302 patients undergoing BMA who presented with mandibular fractures at the Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, from March 2014 to January 2022, were retrospectively analyzed for the onset of ARONJ after tooth extraction. The following variables were investigated as attributes: anatomy, health status, and dental treatment. The correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and the factors related to the onset of ARONJ were identified. The incidence rate of ARONJ was found to be 3.2%. Hypoparathyroidism was an important factor associated with ARONJ development. Thus, systemic factors are more strongly related to the onset of ARONJ after tooth extraction than local factors

Inhibition of vacuolar-type (H+)-ATPase by the cytostatic macrolide apicularen A and its role in apicularen A-induced apoptosis in RAW 264.7 cells

AbstractApicularen A and the known vacuolar-type (H+)-ATPase (V-ATPase) inhibitor bafilomycin A1 induced apoptosis of RAW 264.7 cells, while apicularen B, an N-acetyl-glucosamine glycoside of apicularen A, was far less effective. Apicularen A inhibited vital staining with acridine orange of the intracellular organelles of RAW 264.7 cells, inhibited the ATP-dependent proton transport into inside-out microsome vesicles, and inhibited the bafilomycin A1-sensitive ATP hydrolysis. The IC50 values of the proton transport were 0.58nM for apicularen A, 13nM for apicularen B, and 0.95nM for bafilomycin A1. Furthermore, apicularen A inhibited the bafilomycin A1-sensitive ATP hydrolysis more potently than apicularen B. F-ATPase and P-ATPase were not inhibited by apicularen A. We concluded that apicularen A inhibits V-ATPase, and thus induces apoptosis in RAW 264.7 cells

The Effectiveness of Pre-Operative Screening Tests in Determining Viral Infections in Patients Undergoing Oral and Maxillofacial Surgery

We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8,$905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV

Angiotensin II inhibits insulin-induced actin stress fiber formation and glucose uptake via ERK1/2

There is crosstalk in intracellular signaling between Angiotensin II (Ang II) and insulin. We hypothesized that the underlying mechanism might be related to changes in cytoskeleton. In the presence of 100 nM of Ang II, insulin-induced glucose uptake was decreased and insulin-induced actin filament organization was inhibited. PKC inhibitors, including GF 109203x and p38 MAPK inhibitor (SB 203580) neither improved insulin-induced actin reorganization nor glucose uptake. In contrast, the Ang II-induced inhibition of glucose uptake and actin filament disorganization was reversed by 10 μmol ERK 1/2 MAPK inhibitor (PD 98059). Pretreatment of Ang II increased ERK1/2 phosphorylation and inhibited insulin-induced Akt phosphorylation. The effect of Ang II on ERK 1/2 phosphorylation was blocked by Ang II type 1 receptor antagonists, RNH 6270 and PD 98059 but not by SB 203580 or Guanosine-5’-O-(2-ThioDiphosphate), a G-protein inhibitor. We next tested the effect of broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM 6001) on Ang II-inhibition of insulin signaling pathway. GM 6001 did not improve Ang II-induced actin filament disorganization and did not inhibit ERK1/2 phosphorylation. From these data in L6 myotube, we conclude that Ang II negatively regulates the insulin signal not through MMP signaling pathway but specifically through MMP-independent ERK 1/2 activation pathway, providing an alternative molecular mechanism for angiotensin-induced insulin resistance