Signal Transduction Mechanisms Underlying Group I mGluR-mediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat

Group I mGluRs (mGluR1 and 5) pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs) in the spinal trigeminal subnucleus oralis (Vo), we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 μM/5 min), activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting. The DHPG-induced increases of sEPSC frequency and amplitude were not NMDA receptor-dependent. The DHPG-induced increase in the frequency of sEPSCs, the presynaptic effect being further confirmed by the DHPG effect on paired-pulse ratio of trigeminal tract-evoked EPSCs, an index of presynaptic modulation, was significantly but partially reduced by blockades of voltage-dependent sodium channel, mGluR1 or mGluR5. Interestingly, PKC inhibition markedly enhanced the DHPG-induced increase of sEPSC frequency, which was mainly accomplished through mGluR1, indicating an inhibitory role of PKC. In contrast, the DHPG-induced increase of sEPSC amplitude was not affected by mGluR1 or mGluR5 antagonists although the long-lasting property of the increase was disappeared; however, the increase was completely inhibited by blocking both mGluR1 and mGluR5. Further study of signal transduction mechanisms revealed that PLC and CaMKII mediated the increases of sEPSC in both frequency and amplitude by DHPG, while IP3 receptor, NO and ERK only that of amplitude during DHPG application. Altogether, these results indicate that the activation of group I mGluRs and their signal transduction pathways differentially regulate glutamate release and synaptic responses in Vo, thereby contributing to the processing of somatosensory signals from orofacial region

Characteristics of blood tests in patients with acute cerebral infarction who developed symptomatic intracranial hemorrhage after intravenous administration of recombinant tissue plasminogen activator

Objective Patients suspected as having acute ischemic stroke usually undergo blood tests, including coagulation-related indexes, because thrombocytopenia and coagulopathy are contraindications for recombinant tissue plasminogen activator (rtPA) administration. We aimed to identify blood test indexes associated with symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke who received intravenous rtPA. Methods This retrospective observational study included patients diagnosed with acute ischemic stroke who were treated with intravenous rtPA at the emergency department of a tertiary hospital in Seoul between February 2008 and January 2018. Blood test indexes were compared between the sICH and non-sICH groups. Logistic regression and receiver-operating characteristic curve analyses were performed. Results In this study, 375 patients were finally included. Of 375 patients, 42 (11.2%) showed new intracranial hemorrhage on follow-up brain computed tomography, of whom 14 (3.73%) had sICH. Platelet count, aspartate aminotransferase and lactate dehydrogenase levels were significantly different between the sICH and non-sICH groups, and platelet count showed statistical significance in the regression analysis. Significantly lower platelet counts were observed in the sICH group than in the non-sICH group (174,500 vs. 228,000/mm3, P=0.020). The best cutoff platelet count was 195,000/mm3, and patients with platelet counts of <195,000/mm3 had a 5.4- times higher risk of developing sICH than those with platelet counts of ≥195,000/mm3. Conclusion Platelet count was the only independent parameter associated with sICH among the blood test indexes. Mild thrombocytopenia may increase the risk of sICH after intravenous administration of rtPA

Clinical Significance of Thrombosis in an Intracardiac Blind Pouch After a Fontan Operation

The univentricular heart after the Fontan operation may have a blind pouch formed by the pulmonary stump or rudimentary ventricle according to the anatomy before surgery. Thrombosis in an intracardiac blind pouch of patients with a univentricular heart is a hazardous complication. Because only a few reports have described this complication, the authors evaluated the clinical significance of thrombosis in an intracardiac blind pouch of a univentricular heart. They performed a retrospective review of medical records from August 1986 to December 2007. Four patients were confirmed as having thrombosis in a pulmonary artery stump and one patient as having thrombosis in a rudimentary ventricle shown by cardiac computed tomography (CT). This represents 1.85% (5/271) of patients with ongoing regular follow-up evaluation after the Fontan operation. The median age at diagnosis was 14.2 years. Two of the five patients were taking aspirin and one patient was taking warfarin when they were identified for the development of thrombosis. None of the patients demonstrated thrombosis in the Fontan tract or venous side of the circulation. Brain magnetic resonance imaging (MRI) showed that three patients had cerebral infarction and one patient had suggestive old ischemia. Three patients with thrombus in the pulmonary stump underwent pulmonary artery stump thrombectomy and pulmonary valve obliteration. One patient with thrombus in the rudimentary ventricle underwent ventricular septal defect (VSD) closure with thrombectomy. Thrombus in a blind pouch could cause systemic thromboembolism despite little blood communication. Therefore, surgical modification of the pulmonary stump and VSD closure of the rudimentary ventricle are required to reduce the risk of later thrombus formation. Clinicians should not overlook the possibility of thrombus in a ligated pulmonary artery stump or a rudimentary ventricle after the Fontan operation, which may increase the risk of embolic stroke for patients with single-ventricle physiology

The Incidence of Gastro-Esophageal Disease for the Patients with Typical Chest Pain and a Normal Coronary Angiogram

Background : Although patients may present with typical chest pain and exhibit ischemic changes on the cardiac stress test, they are frequently found to have a normal coronary angiogram. Thus, we wanted to determine which procedures should be performed in order to make an adequate diagnosis of the cause of chest pain. Methods : 121 patients (males: 42, 34.7%) who had a normal coronary angiogram with typical chest pain were included in this study. All the patients underwent upper endoscopy, Bernstein&apos;s test and esophageal manometry. Results : Among the 121 patients, clinically stable angina was noted in 107 (88.4%). Stress testing was done in 82 (67.8%); it was positive in 52 (63.4%). Endoscopic findings were erosive gastritis in 18 (14.8%), gastric ulcer in 4 (3.3%), duodenal ulcer in 5 (4.1%), and reflux esophagitis in 16 (13.2%). Positive results were observed on Berstein&apos;s test for 68 patients (56.2%); 59 (86.8%) of them had non-erosive reflux disease. On the esophageal manometry, 35 (28.9%) of these patients had motility disorders. Nutcracker esophagus was observed in 27 patients (22.3%), nonspecific esophageal motility disorder was observed in 5 (4.1%), and hypertensive lower esophageal sphincter was observed in 3 (2.5%). Among the 52 patients with positive cardiac stress testing and a negative coronary angiogram (this clinically corresponded to microvascular angina), 46 patients (85.1%) showed abnormal findings on the gastro-esophageal studies. Conclusions : In our study, 85.1% of the patients with microvascular angina revealed positive results of gastric or esophageal disease. In spite of any existing evidence of microvascular angina or cardiac syndrome X, it would be more advisable to perform gastro-esophageal studies to adequately manage chest pain

Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

Background/AimsWhile gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.MethodsThe data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.ResultsThe initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).ConclusionsThe clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis

Skin Moisturizing Effects of a Microneedle Patch Containing Hyaluronic Acid and Lonicerae flos

The utilization of cosmetic raw materials for medicinal purposes in a microneedle patch containing hyaluronic acid (HA) and Lonicerae flos ethanol extract (LEE) has increased based on their eco-friendly characteristics. The moisturizing effects of this microneedle patch were assessed on the forearms of 20 female participants, and our results showed an increase between 29.60% and 88.54% in skin moisture content at the same time points relative to the untreated group. Apart from confirming the safety of HA and Lonicerae flos, our findings may also promote the use of HA and medicinal herbs in relevant industries, indicating their potential as raw ingredients for the development of cosmetic products and topical dermatological drugs. The results suggested that HA, Lonicerae flos, and other combinations of chemical and natural products based on traditional oriental medicine could beneficially affect skin health

Electrical contact resistance of a thin oxide layer with a low mechanical load

The electrical contact resistance of a vertical binary contact between stainless steel balls with a low mechanical load was investigated. Using a statistical approach, we measured the voltage at which the dielectric breakdown occurs within a thin surface oxide layer and the distribution of the contact resistance. Electrical load-bearing conduction through a thin insulating layer was found to occur through two possible sequential processes. In both cases, once a conduction path is formed, the melting of bridges as in conventional contact theory is involved. This suggests that conduction through an oxide layer with a low mechanical load depends mainly on breakdown-induced bridges. Furthermore, the distribution of such path’s resistance shows the log-normal distribution with a long tail toward high resistance