Zebrafish as an animal model in epilepsy studies with multichannel EEG recordings

Despite recent interest in using zebrafish in human disease studies, sparked by their economics, fecundity, easy handling, and homologies to humans, the electrophysiological tools or methods for zebrafish are still inaccessible. Although zebrafish exhibit more significant larval-adult duality than any other animal, most electrophysiological studies using zebrafish are biased by using larvae these days. The results of larval studies not only differ from those conducted with adults but also are unable to delicately manage electroencephalographic montages due to their small size. Hence, we enabled noninvasive long-term multichannel electroencephalographic recording on adult zebrafish using customdesigned electrodes and perfusion system. First, we exploited demonstration of long-term recording on pentylenetetrazole-induced seizure models, and the results were quantified. Second, we studied skin- electrode impedance, which is crucial to the quality of signals. Then, seizure propagations and gender differences in adult zebrafish were exhibited for the first time. Our results provide a new pathway for future neuroscience research using zebrafish by overcoming the challenges for aquatic organisms such as precision, serviceability, and continuous water seepage. © The Author(s) 2017.1

Prefrontal functional connectivity analysis of cognitive decline for early diagnosis of mild cognitive impairment: A functional near-infrared spectroscopy study

Cognitive decline (CD) is a major symptom of mild cognitive impairment (MCI). Patients with MCI have an increased likelihood of developing Alzheimer's disease (AD). Although a cure for AD is currently lacking, medication therapies and/or daily training in the early stage can alleviate disease progression and improve patients' quality of life. Accordingly, investigating CD-related biomarkers via brain imaging devices is crucial for early diagnosis. In particular, “portable” brain imaging devices enable frequent diagnostic checks as a routine clinical tool, and therefore increase the possibility of early AD diagnosis. This study aimed to comprehensively investigate functional connectivity (FC) in the prefrontal cortex measured by a portable functional near-infrared spectroscopy (fNIRS) device during a working memory (WM) task known as the delayed matching to sample (DMTS) task. Differences in prefrontal FC between healthy control (HC) (n = 23) and CD groups (n = 23) were examined. Intra-group analysis (one-sample t-test) revealed significantly greater prefrontal FC, especially left- and inter-hemispheric FC, in the CD group than in the HC. These observations could be due to a compensatory mechanism of the prefrontal cortex caused by hippocampal degeneration. Inter-group analysis (unpaired two-sample t-test) revealed significant intergroup differences in left- and inter-hemispheric FC. These attributes may serve as a novel biomarker for early detection of MCI. In addition, our findings imply that portable fNIRS devices covering the prefrontal cortex may be useful for early diagnosis of MCI. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement1

Inhibitory effect of positively charged triazine antagonists of prokinecitin receptors on the transient receptor vanilloid type-1 (TRPV1) channel

Four positively charged compounds, previously shown to produce analgesic activity by interacting with prokinecitin receptor or T-type calcium channels, were tested for their ability to inhibit capsaicin-induced elevation of intracellular Ca(2+) elevation in HEK-293 cells stably transfected with the human recombinant TRPV1, with the goal of identifying novel TRPV1 open-pore inhibitors. KYS-05090 showed the highest potency as a TRPV1 antagonist, even higher than that of the open-pore triazine 8aA inhibitor. The latter showed quite remarkable agonist/desensitizer activity at the rat recombinant TRPM8 channel. The activity of KYS-05090 and the other compounds was selective because none of these compounds was able to modulate the rat TRPA1 channel. Open-pore inhibitors of TRPV1 may be a new class of multi-target analgesics with lesser side effects, such as loss of acute pain sensitivity and hyperthermia, than most TRPV1 antagonists developed so far

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 +/- 37 mu g/mL at 15 min. The systemic clearance was 347 +/- 117 mL/h/kg, and the steady-state volume of distribution was 223 +/- 67 mL/kg. Dialysis clearance was 71.1 +/- 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 +/- 0.150. The half-life (T-1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.OAIID:RECH_ACHV_DSTSH_NO:T201621129RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A003050CITE_RATE:1.279FILENAME:Byun_et_al-2016-Journal_of_Veterinary_Pharmacology_and_Therapeutics.pdfDEPT_NM:수의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/eb2b2d93-6cb2-4420-a374-90eb43215957/linkCONFIRM:

Subarachnoid Hemorrhage Mimicking Leakage of Contrast Media After Coronary Angiography

We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days

Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B

Background/Aims Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response. Methods This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10 IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal. Results After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log10 IU/mL (n=11) and >3 log10 IU/mL (n=28), respectively. Conclusion The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log10 IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration