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:

Deep learning based prediction of prognosis in nonmetastatic clear cell renal cell carcinoma

Abstract Survival analyses for malignancies, including renal cell carcinoma (RCC), have primarily been conducted using the Cox proportional hazards (CPH) model. We compared the random survival forest (RSF) and DeepSurv models with the CPH model to predict recurrence-free survival (RFS) and cancer-specific survival (CSS) in non-metastatic clear cell RCC (nm-cRCC) patients. Our cohort included 2139 nm-cRCC patients who underwent curative-intent surgery at six Korean institutions between 2000 and 2014. The data of two largest hospitals’ patients were assigned into the training and validation dataset, and the data of the remaining hospitals were assigned into the external validation dataset. The performance of the RSF and DeepSurv models was compared with that of CPH using Harrel’s C-index. During the follow-up, recurrence and cancer-specific deaths were recorded in 190 (12.7%) and 108 (7.0%) patients, respectively, in the training-dataset. Harrel’s C-indices for RFS in the test-dataset were 0.794, 0.789, and 0.802 for CPH, RSF, and DeepSurv, respectively. Harrel’s C-indices for CSS in the test-dataset were 0.831, 0.790, and 0.834 for CPH, RSF, and DeepSurv, respectively. In predicting RFS and CSS in nm-cRCC patients, the performance of DeepSurv was superior to that of CPH and RSF. In no distant time, deep learning-based survival predictions may be useful in RCC patients

Kv3.1 and Kv3.4, Are Involved in Cancer Cell Migration and Invasion

Voltage-gated potassium (Kv) channels, including Kv3.1 and Kv3.4, are known as oxygen sensors, and their function in hypoxia has been well investigated. However, the relationship between Kv channels and tumor hypoxia has yet to be investigated. This study demonstrates that Kv3.1 and Kv3.4 are tumor hypoxia-related Kv channels involved in cancer cell migration and invasion. Kv3.1 and Kv3.4 protein expression in A549 and MDA-MB-231 cells increased in a cell density-dependent manner, and the pattern was similar to the expression patterns of hypoxia-inducible factor-1α (HIF-1α) and reactive oxygen species (ROS) according to cell density, whereas Kv3.3 protein expression did not change in A549 cells with an increase in cell density. The Kv3.1 and Kv3.4 blocker blood depressing substance (BDS) did not affect cell proliferation; instead, BDS inhibited cell migration and invasion. We found that BDS inhibited intracellular pH regulation and extracellular signal-regulated kinase (ERK) activation in A549 cells cultured at a high density, potentially resulting in BDS-induced inhibition of cell migration and invasion. Our data suggest that Kv3.1 and Kv3.4 might be new therapeutic targets for cancer metastasis

Nano-Interstice Driven Powerless Blood Plasma Extraction in a Membrane Filter Integrated Microfluidic Device

Blood plasma is a source of biomarkers in blood and a simple, fast, and easy extraction method is highly required for point-of-care testing (POCT) applications. This paper proposes a membrane filter integrated microfluidic device to extract blood plasma from whole blood, without any external instrumentation. A commercially available membrane filter was integrated with a newly designed dual-cover microfluidic device to avoid leakage of the extracted plasma and remaining blood cells. Nano-interstices installed on both sides of the microfluidic channels actively draw the extracted plasma from the membrane. The developed device successfully supplied 20 μL of extracted plasma with a high extraction yield (~45%) in 16 min

Evaluation of multi-RCM ensembles for simulating spatiotemporal variability of Asian summer monsoon precipitation in the CORDEX-East Asia Phase 2 domain

Five regional climate models (RCMs)-CCLM, RegCM, HadGEM3-RA, SNURCM and WRF-participating in the Coordinated Regional Climate Downscaling Experiment-East Asia (CORDEX-EA) Phase 2 project are evaluated for their ability to simulate spatiotemporal variability in Asian summer precipitation. For this purpose, two dynamical downscaling sets, experiments forced by ERA-Interim reanalysis data (reproduction experiment) and historical data from three Coupled Model Intercomparison Project 5 (CMIP5) general circulation models (GCMs) (historical experiment) are analysed. The horizontal resolution of the downscaled results is 25 km, and the analysis period is from 1981 to 2005 (25 years). The RCMs show reasonable performance in simulating the spatial and temporal characteristics of summer precipitation in CORDEX-EA Phase 2 domain. To assess spatiotemporal patterns in Asian precipitation, cyclostationary empirical orthogonal function (CSEOF) analysis is used. In the first mode representing seasonal variations, the model ensemble results of both the reproduction experiment (Rep_ENS) and the historical experiment (His_ENS) simulate the peak times, location of precipitation and progression of the monsoons in Asia reasonably. Their features are greatly influenced by the moisture flux, indicating that the relation between precipitation and 850 hPa moisture flux is depicted well by RCM ensembles. In the second mode, which represents intraseasonal variations, the Rep_ENS depicts the western North Pacific summer monsoon break (WNPSM break) phenomenon similar to the observation. Although the His_ENS simulates the WNPSM break later than the observation, it does present the intraseasonal variation in the East Asian summer monsoon region. Based on these results, the five RCM ensemble results show the ability to capture spatiotemporal characteristics of summer precipitation in CORDEX-EA Phase 2 domain, as well as added value from dynamical downscaling

Influence of androgen deprivation therapy on serum urate levels in patients with prostate cancer: A retrospective observational study.

OBJECTIVES:Although estrogenic modulation of serum urate levels is well-known, the androgenic effect on urate homeostasis remains controversial. We investigated the effect of androgen deprivation therapy (ADT) on serum urate levels. METHODS:We retrospectively enrolled a total of 489 prostate cancer patients with available serum urate levels at baseline and 3 and 6 months after ADT (n = 150) or prostate surgery (n = 339). We extracted the demographic, clinical, and laboratory data from a data warehouse and compared the changes in urate levels between the two treatment groups and between the different ADT regimens (with versus without luteinizing hormone-releasing hormone (LHRH) agonists) using generalized estimating equation (GEE). RESULTS:The baseline urate levels and the proportion of hyperuricemic subjects were comparable between the two groups. After 6 months, the urate levels were significantly decreased (by -0.66 mg/dL, 95% confidence interval (CI) [-0.81 to -0.51]) in the ADT group, whereas they did not significantly change in the surgery group in the univariate GEE analysis. The ADT group (4.7% from 18.0% at baseline) had a significantly lower proportion of hyperuricemic patients than surgery group (16.5% from 15.9% at baseline) at 6-month (p < 0.001). Regardless of whether LHRH agonists were used, the serial urate levels were lowered by the ADT. Temporal changes in the urate levels were significantly associated with the treatment group, baseline hyperuricemia, and poor functional or advanced cancer status. The ADT-related serum urate level reduction also remained significant in the multivariate GEE analysis (regression coefficient = -0.43 [-0.67 to -0.19] after 3 months and -0.37 [-0.64 to -0.10] after 6 months). Moreover, propensity-score-matched analyses yielded the same results. CONCLUSIONS:Our results showed that longitudinal serum urate levels were significantly reduced in men receiving ADT. This finding suggests that androgen could have an independent role in urate homeostasis

Nonarteritic anterior ischemic optic neuropathy is associated with cerebral small vessel disease.

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p<0.001), which was also observed after adjusting for age, sex, comorbid conditions including hypertension, diabetes, and dyslipidemia, and smoking using the standardized mortality ratio (68% vs. 37%, p<0.001). A multivariate logistic regression analysis showed that the odds of cerebral SVD were 4.86 (95% CI, 2.10 to 11.24, p<0.001) times higher in patients with NAION than in the controls. We found that there was an association between cerebral SVD and NAION even after adjusting for age, sex, and medical histories. Clinicians should consider brain MRI scans in patients with NAION to prevent neurological impairment after cerebral SVD