Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs

Background Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. Results The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). Conclusions These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure

Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut–liver axis of alcoholic liver disease

AbstractBackgroundRoles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD).MethodsWe evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a Lieber–DeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared.ResultsNo between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group (0.37 ± 0.06 ng/mL, 0.39 ± 0.12 ng/mL, and 0.33 ± 0.07 ng/mL, respectively, vs. 0.88 ± 0.31 ng/mL; p < 0.05). Interleukin-1β levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-α level of liver tissue was decreased in the KRG group.ConclusionThe pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments

Biliary complications in living donor liver transplantation: imaging findings and the roles of interventional procedures

PURPOSE: To describe the incidence, types, and findings of biliary complications in living donor liver transplantation (LDLT) and to determine the roles of interventional procedures. MATERIALS AND METHODS: Twenty-four biliary complications among 161 LDLT patients (24/161, 14.9%) were identified. These complications were divided into two groups according to the initial manifestation time, i.e., "early" (<60 days) or "late". The CT and cholangiographic findings were reviewed regarding the presence of a stricture or leak and the location, and length, shape, and degree of the stricture. Both groups were categorized into three subgroups: leak, stricture, and both. The type of interventional procedures used and their roles were determined. RESULTS: Early complications were identified in 14 of the 24 patients (58%) and late complications in 11 (46%). One patient showed both early and late complications. Biliary stricture was detected in 10 patients, leak in 10, and both in 5. By cholangiography, all strictures were irregular and short (mean length 15 +/- 6 mm) at the anastomotic site and complete obstruction was observed in 2 patients with late stricture. Twenty-three of the 24 patients were treated using percutaneous and/or endoscopic drainage procedures with or without balloon dilatation. Seventeen (74%) showed a good response, but reoperations were inevitable in 6 (26%). All patients except those with complete obstruction showed a favorable outcome after interventional management. CONCLUSION: Biliary leaks and strictures are predominant complications in LDLT. Most show good responses to interventional treatment. However, complete obstruction needs additional operative management

Stereotactic Body Radiotherapy for Isolated Para-aortic Lymph Node Recurrence after Curative Resection in Gastric Cancer

The aim of this study was to investigate whether stereotactic body radiotherapy (SBRT) can salvage gastric cancer patients with para-aortic lymph node (PALN) recurrence. From January 2003 to December 2006, 7 patients were treated for isolated PALN recurrence from gastric cancer after curative resection. Follow up durations ranged from 19 to 33 months (median; 26 months), and SBRT doses from 45 Gy to 51 Gy (median 48 Gy) in 3 fractions. Disease progression-free and overall survivals and toxicities were recorded. Response to treatment was assessed by computed tomography. Final patient outcomes were as follows: 2 were alive without evidence of disease, 3 remained alive with disease, and 2 patients died of disease. Five of 7 patients showed complete response and 2 patients partial response between 3 and 11 months after SBRT. Three-year overall and disease progression-free survival rates post-SBRT were 43% and 29%, respectively. No severe complication was detected during follow-up. Selected patients with isolated PALN recurrence can be salvaged by SBRT without severe complications

The genome sequence of Xanthomonas oryzae pathovar oryzae KACC10331, the bacterial blight pathogen of rice

The nucleotide sequence was determined for the genome of Xanthomonas oryzae pathovar oryzae (Xoo) KACC10331, a bacterium that causes bacterial blight in rice (Oryza sativa L.). The genome is comprised of a single, 4 941 439 bp, circular chromosome that is G + C rich (63.7%). The genome includes 4637 open reading frames (ORFs) of which 3340 (72.0%) could be assigned putative function. Orthologs for 80% of the predicted Xoo genes were found in the previously reported X.axonopodis pv. citri (Xac) and X.campestris pv. campestris (Xcc) genomes, but 245 genes apparently specific to Xoo were identified. Xoo genes likely to be associated with pathogenesis include eight with similarity to Xanthomonas avirulence (avr) genes, a set of hypersensitive reaction and pathogenicity (hrp) genes, genes for exopolysaccharide production, and genes encoding extracellular plant cell wall-degrading enzymes. The presence of these genes provides insights into the interactions of this pathogen with its gramineous host

New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry.Materials and methodsThis is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model.ResultsAmong 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38–3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60–4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p &lt; 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality.ConclusionThe GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system

The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy

Hydrofluoroether-assisted dilution of Na-ion concentrated ionic liquid electrolyte for safe, stable cycling of high-voltage Na-metal batteries

Sodium (Na)-powered rechargeable batteries (NRBs) are promising as sustainable energy storage systems. To overcome an inherent energy density handicap of NRBs, increasing cell voltage is necessary by building a Na metal battery (NMB), which simultaneously features coveted high-voltage stability and efficient Na dendrite protection. Although ionic liquids (ILs) are eligible to provide superior oxidative stability, their practical uses are challenging due to high viscosity and sluggish ionic transport at a higher Na concentration. Here, a localized Na+ ion concentrated ionic liquid (LNCIL) electrolyte consisting of an IL and a hydrofluoroether (HFE) as cosolvents is developed. The addition of a non-solvating HFE lowers the viscosity and improves separator wettability, thereby facilitating Na+ ion transport. Furthermore, HFE dilution promotes the involvement of dual anions (FSI/TFSI) in the development of a protective solid-electrolyte interphase, leading to Na dendrite suppression. A Na||Na3V2(PO4)3 cell incorporating the LNCIL electrolyte demonstrates excellent cyclability (~96.6% capacity retention over 500 cycles). Moreover, with oxidative stability up to 4.9 V (vs. Na/Na+) and non-flammability, the LNCIL electrolyte ensures the safe operation of high-voltage NMBs. © 2021FALS