Oligodendroglial GABAergic Signaling: More Than Inhibition! / 神经科学通报·英文版

GABA is the main inhibitory neurotransmitter in the CNS acting at two distinct types of receptor: ligand-gated ionotropic GABA

Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway / 神经科学通报·英文版

The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.

Clinical Implications of New Drugs and Regimens for the Treatment of Drug-resistant Tuberculosis / 전남의대학술지

The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB. This review covers promising novel TB drugs and regimens that are currently under development. Bedaquiline and delamanid are the most promising novel drugs for the treatment of MDR-TB, each having a high efficacy and tolerability. However, the best regimen for achieving better outcomes and reducing adverse drug reactions remains yet to be determined, with safety concerns regarding cardiac events due to QT prolongation still to be addressed. Pretomanid is a novel drug that potentially shortens the duration of treatment in both drug-susceptible and drug-resistant TB. Many regimens consisting of injection free drugs with shorter treatment duration compared to the conventional treatment are now undergoing clinical trials. Therefore a simple and short treatment with higher efficacy, and lesser adverse drug reactions and drug-drug interaction is expected for patients with MDR-TB.

Clinical Implications of New Drugs and Regimens for the Treatment of Drug-resistant Tuberculosis / 전남의대학술지

The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB. This review covers promising novel TB drugs and regimens that are currently under development. Bedaquiline and delamanid are the most promising novel drugs for the treatment of MDR-TB, each having a high efficacy and tolerability. However, the best regimen for achieving better outcomes and reducing adverse drug reactions remains yet to be determined, with safety concerns regarding cardiac events due to QT prolongation still to be addressed. Pretomanid is a novel drug that potentially shortens the duration of treatment in both drug-susceptible and drug-resistant TB. Many regimens consisting of injection free drugs with shorter treatment duration compared to the conventional treatment are now undergoing clinical trials. Therefore a simple and short treatment with higher efficacy, and lesser adverse drug reactions and drug-drug interaction is expected for patients with MDR-TB.

Pharmacokinetic characteristics of cilostazol 200 mg controlled-release tablet compared with two cilostazol 100 mg immediate-release tablets (Pletal) after single oral dose in healthy Korean male volunteers

Cilostazol controlled-release (CR) tablets have recently been developed by Korea United Pharm (Seoul, Korea). The tablets use a patented double CR system, which improves drug compliance by allowing "once daily" administration and reduces adverse events by sustaining a more even plasma concentration for 24 h. We conducted an open, randomized, two-period, two-treatment, crossover study to compare the pharmacokinetic (PK) characteristics and tolerability of cilostazol when administered to healthy Korean male volunteers as CR or immediate release (IR) tablets (Pletal, Korea Otsuka Pharmaceutical Co., Gyeonggi-do, Korea). Each volunteer was randomly allocated to receive a single tablet of cilostazol CR (200 mg) or two tablets of cilostazol IR (100 mg) with a 7-day washout period between treatments. Plasma cilostazol, OPC-13015 (3,4-dehydrocilostazol), and OPC-13213 (4'-trans-hydroxycilostazol) were assayed using liquid chromatography-tandem mass spectrometry for PK analysis. Thirty participants completed the study with no clinically relevant safety issues. The peak concentrations (C(max), mean ± SD) of cilostazol CR and cilostazol IR were 1414.6 ± 49.3 and 1413.1 ± 35.2 ng/mL, respectively, and the areas under the plasma concentration-time curve from 0 to the last concentration (AUC(last)) were 23928.7 ± 65.9 and 25312.0 ± 62.6 ng·h/mL, respectively. The geometric mean ratios (cilostazol CR/cilostazol IR, GMR) of the C(max) and AUC(last) values were 1.001 (90% CI: 0.822, 1.220) and 0.945 (90% CI: 0.814, 1.098), respectively. The frequencies of adverse events were similar. The present study showed that cilostazol PK and tolerability were comparable when administered to healthy Korean men, regardless of whether administered as cilostazol CR or IR.

Management of organophosphorus compound poisoning -A one year experience in a tertiary care hospital.

This study was undertaken to assess the distribution pattern, outcome and possible predictors affecting the mortality and the need for ventilator support in patients who had consumed organophosphorus compound pesticides. 91 patients who were admitted to the ICU between April 2009 and March 2010 with history of ingestion of organophosphorus pesticide, were studied. Baseline clinical assessment and investigations were undertaken and SOFA and APACHE II scores were calculated. Out of 91 patients, 39 required ventilator support. Of these 39 patients, 2 died, one due to severe sepsis and multiorgan dysfunction, and the other, a chronic alcoholic with chronic liver disease, due to hepatic encephalopathy and multiorgan dysfunction. The time elapsed since ingestion of poison, SOFA and APACHE II scores were significantly associated with patients requiring ventilator support. However with logistic regression analysis, none of these variables were able to either predict mortality or the need for ventilator support. The overall outcome in these cases was favourable as the mortality rate was 2.3%. Though the time elapsed since ingestion of the pesticide and the APACHE II score were found to predict the need for ventilation in many earlier studies, they failed to predict either the need for ventilation or mortality in the present study. The improved mortality rate could be attributed to an organized approach through protocols between the emergency department and the ICU in order to successfully manage patients with organophosphorus compound poisoning.

The Effect of Oxytocin on Subcellular Localization of Aquaporin-2 in Rat Kidney: an Ultrastructural Immunocytochemical Study / 대한신장학회잡지

BACKGROUND: The aquaporin-2 (AQP2) water channel is mainly located in the apical plasma membrane of epithelial cells in the connecting tubule and collecting ducts, but there has been some evidence of a moderate amount of basolateral localization of AQP2 in these nephron segments. Previous in vitro microperfusion studies showed that oxytocin has an antidiuretic action most likely mediated by the vasopressin V2 receptor (V2R) in rat inner medullary collecting duct. METHODS: By using ultrastructural preembedding immunocytochemistry with 1 nm immunogold in male Sprague-Dawley rat kidneys, we investigated the acute (60 min) effect of oxytocin (10 U) on the subcellular localization of AQP2 and tested whether the effect of oxytocin is prevented by a V2R antagonist, OPC-31260 (OPC). RESULTS: In control rat kidneys, AQP2 was mainly expressed in the apical plasma membrane and subapical vesicles in the connecting tubule (CNT) cells, principal cells of cortical (CCD), outer medullary collecting duct (OMCD) and initial part of inner medullary collecting duct (IMCD), and IMCD cells of terminal part of IMCD. Basolateral AQP2 labeling was observed in the CNT cells and IMCD cells. In contrast, there was little basolateral AQP2 labeling in the CCD and OMCD principal cells. Oxytocin treatment induced apical immunolabeling of AQP2 and caused an increase of AQP2 immunolabeling in the basal part including basolateral plasma membrane in the CNT cells, principal cells of CCD, OMCD and initial part of IMCD, and IMCD cells of terminal part of IMCD. Pretreatment of rats with a V2R antagonist OPC before oxytocin treatment caused translocation of AQP2 from the apical plasma membrane to the subapical vesicles. However, AQP2 labeling of basolateral plasma membrane was unchanged or slightly increased. CONCLUSION: Oxytocin induces an increase of AQP2 expression not only in the apical plasma membrane but also in the basolateral plasma membrane. Pretreatment with a V2R antagonist blocked redistribution of apical AQP2 immunolabeling, but did not cause retrieval of AQP2 from the basolateral plasma membrane. These results suggest that apical and basal targeting of AQP2 are regulated by different mechanisms.

A STUDY ON THE MARGINAL FIT OF ALL-CERAMIC CROWN USING CCD CAMERA / 대한치과보철학회지

The purpose of this study was to evaluate marginal fit of four all-ceramic crown systems 1) conventional In-Ceram, 2) copy-milled In-Ceram using Celay system, 3) IPS Empress, 4) OPC(Optimal Pressable Ceramic). All ceramic crowns were made on epoxy dies. The fabricated crowns were sandblasted, cleaned with ultrasonic cleansing, silanated, and cemented with Bistite composite resin cement. The selected marginal areas of the crowns were the labial, lingual, mesial, and distal surface. Each selected area of surface was 0.6Xl.6mm in dimension. The image of each marginal area was captured to computer files using DT-55 Frame Grabber and light microscope connected CCD camera. The marginal gaps were measured every 70mm using computer image analysis program. The results obtained were summarized as follows : 1. The marginal fit of four all-ceramic crowns were significantly different from each other(p<0.01), and mean marginal fit values obtained were 31.42 +/- 16.52mm in conventional In-Ceram, 55.45 +/- 27.90mm in copy-milled In-Ceram using Celay-system, 44.36 +/- 24.59mm in IPS Empress, 47.21 +/- 20.42mm in OPC. 2. In the marginal fit of conventional In-Cerani and copy-milled In-Ceram crowns using Celay-system there was no significant difference between mesiodistal and buccolingual surface. but in the marginal fit of IPS Empress and OPC crowns, there was significant difference between mesiodistal and buccolingual surface(p <0.01). 3. The marginal fit of four hinds of all-ceramic crowns was clinically acceptable.