Acute phase response in bovine coronavirus positive post-weaned calves with diarrhea

Bovine coronavirus (BCoV) is associated with severe diarrhea in calves, winter dysentery in adult cattle, and respiratory diseases in cattle of all ages. This study aimed to investigate the relationship between white blood cell counts and haptoglobin (Hp) and serum amyloid A (SAA) levels in post-weaned calves with diarrhea caused by BCoV and those that recovered from diarrhea. Blood and fecal samples were collected twice from the same animals; 17 post-weaned calves with diarrhea (first) and 15 post-weaned calves that recovered from diarrhea (second). Real-time polymerase chain reaction revealed that all 17 fecal samples from post-weaned calves with diarrhea and one out of 15 from diarrhea-recovered calves were positive for BCoV and negative for Cryptosporidium spp., Escherichia coli K99, Salmonella spp., bovine rotavirus, and bovine viral diarrhea virus. No Eimeria oocysts were detected using the flotation method. In comparison with post-weaned calves with diarrhea, in diarrhea-recovered calves, the lymphocyte count was significantly higher (P = 0.018), and the monocyte count was significantly lower (P = 0.001); however, the number of monocytes was still high. Post-weaned calves with diarrhea had a significantly higher Hp concentration (P < 0.001) compared with diarrhea-recovered calves. The results indicated that increased Hp concentration and monocytosis but not SAA may be associated with diarrhea caused by BCoV. The present study suggests that the monitoring of Hp concentration and monocyte count is useful in the diagnosis of post-weaned calves with diarrhea caused by BCoV in this field.This study was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2017R1A2B2005685)

Light-chain amyloidosis presenting with rapidly progressive submucosal hemorrhage of the stomach

SummaryThe gastrointestinal tract is frequently in involved light-chain (AL) amyloidosis, but significant hemorrhagic complications are rare. A 71-year-old man presented to our hospital with dyspepsia and heartburn for 1 month. Gastroscopy revealed a large submucosal hematoma at the gastric fundus. Two days later, a follow-up gastroscopy indicated extensive expansion of the hematoma throughout the upper half of the stomach. The hematoma displayed ongoing expansion during the endoscopic examination, suggesting that rupture was imminent. Emergency total gastrectomy was performed, and amyloidosis was confirmed after examining the surgical specimen. Bone marrow examination revealed multiple myeloma, and serum immunoglobulin assay confirmed the diagnosis of myeloma-associated AL amyloidosis. At manuscript submission, the patient was doing well and was undergoing chemotherapy

Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats

The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethyl-benzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following intravenous and oral administrations to rats. The plasma concentrations of both analytes were analyzed via high-performance liquid chromatography coupled with photodiode-array detection (HPLC-DAD). When VP-0502 was intravenously administered at 20 mg/kg, the analyte appeared in low levels with an AUC of 0.3 µg · h/ml, and C0 of 0.2 µg/ml in plasma. However, both the prodrug VP-0502AL and its metabolite VP-0502 appeared at comparatively higher levels following intravenous injection of VP-0502AL at the same dose. VP-0502AL's pharmacokinetic parameters were Vd: 4.6 l/kg; AUC: 3 µg · h/ml; t1/2: 0.5 h; C0: 6 µg/ml; CLtot: 7 l/h/kg; and MRT: 0.6 h. Following oral administration of VP-0502 (100 mg/kg), it was not detectable in plasma (<50 ng/ml), while after the oral administration of VP-0502AL, VP-0502 was quantitatively detected as an active metabolite for the first 7 h, with a maximum plasma concentration (Cmax) of 0.8 µg/ml, and an area under the concentration-time curve (AUC) of 2 µg · h/ml. The oral pharmaco-kinetic parameters of VP-0502AL were calculated to be: maximum concentration time (tmax) 2.7 h; Cmax 0.2 µg/ml; elimination half-life (t1/2): 0.8 h; and AUC 0.5 µg · h/ml. Overall the findings indicate that VP-0502AL has a favorable pharmacokinetic profile as a prodrug with rapid transformation into the active metabolite, and that the attachment of the amino acid alanine to VP-0502 is an effective approach to improve its oral bioavailability. VP-0502AL is predicted to become a new highly bioavailable anti-AIDS drug candidate and/or lead compound

The Effects of Acupuncture Stimulation for Brain Activation and Alcohol Abstinence Self-Efficacy: Functional MRI Study

We attempted to investigate whether acupuncture stimulation at HT7 can have an effect on brain activation patterns and alcohol abstinence self-efficacy. Thirty-four right-handed healthy subjects were recruited for this study. They were randomly assigned into two groups: the HT7 (Shenmen) group and the LI5 (Yangxi) group. Acupuncture stimulation was performed using a block paradigm during fMRI scanning. Additionally, the Korean version of Alcohol Abstinence Self-Efficacy Scale (AASES) was used to determine the effect of acupuncture stimulation on self-efficacy to abstain from alcohol use. According to the result of fMRI group analysis, the activation induced by HT7 stimulation was found on the bilateral postcentral gyrus, inferior parietal lobule, inferior frontal gyrus, claustrum, insula, and anterior lobe of the cerebellum, as well as on the left posterior lobe of the cerebellum (p<0.001, uncorrected). According to the AASES analysis, the interaction effect for gender and treatment was marginally significant (F(1,30)=4.152, p=0.050). For female group, the simple main effect of treatment was significant (F(1,11)=8.040, p=0.016), indicating that the mean change score was higher in the HT7 stimulation than in the LI5 stimulation. Therefore, our study has provided evidence to support that HT7 stimulation has a positive therapeutic effect on the alcohol-related diseases

Scutellaria baicalensis

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of Scutellaria baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of S. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of S. baicalensis compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the S. baicalensis extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function

Disability of Hearing Impairment Is Positively Associated With Urine Albumin/Creatinine Ratio in Korean Adults: The 2011–2012 Korea National Health and Nutrition Examination Survey

Objectives. The aim of this study was to determine whether chronic kidney disease (CKD) is associated with hearing thresholds in the nationwide, large-scaled Korean population. Methods. This study analyzed the data of 9,798 subjects of 19 years and older (4,387 males and 5,411 females). Urine albumin-to-creatinine ratio (ACR) was measured from first-voided spot urine samples. The air-conduction hearing threshold was measured at 0.5, 1, 2, 3, 4, and 6 kHz and pure tone audiogram (PTA) average was calculated as the four-frequency average of 0.5, 1, 2, and 4 kHz. Results. Urine ACR was significantly correlated with the PTA average of better ear in both genders, especially at 3 and 6 kHz in males and at 1, 3, 4, and 6 kHz in females. After adjusting, urine ACR also increased the risk of hearing loss in female, especially if urine ACR was 30 mg/g and more (odds ratio, 1.636–2.229. This study showed that the degree of hearing loss was significantly different according to categories of urine ACR in both genders. Hearing loss without disability was found less but that with bilateral hearing disability was found more as urine ACR increased. In generally, prevalence of hearing loss with disability was higher in males than females. Conclusion. This study demonstrated that urine ACR was significantly correlated with the PTA average of better ear in Korean adults of both genders. This study suggests that clinicians should carefully monitor the hearing level for subjects with elevated urine ACR, even though high urine ACR within the normal range

Aseptic Endocarditis in Behçet's Disease Presenting as Tricuspid Valve Stenosis

Aseptic endocarditis is an uncommon complication of Behçet's disease (BD). We describe a rare case of a 39-year-old female who had BD with aseptic endocarditis of the tricuspid valve (TV) presenting as tricuspid stenosis. She was diagnosed with BD four years ago. The mucocutaneous lesions were well-controlled with colchicine and short courses of corticosteroids. She remained free of signs and symptoms of BD for one year without any medication. Three months before admission, she gradually developed dyspnea on exertion and peripheral edema. Echocardiography revealed dilated right atrium and markedly thickened TV with severe stenosis. TV replacement was performed. Pathologic examination of the valve showed fibrinoid necrotic material and inflammatory cell infiltration. Blood cultures and cultures of the excised valve were negative for microorganisms

The Clinical Characteristics of Optic Neuritis in Korean Children

To study the clinical characteristics of optic neuritis in Korean children. A retrospective review of the medical charts of 20 patients who were diagnosed with optic neuritis before age 10 was conducted in this study. Data were collected on the demographics, clinical features, use of intravenous corticosteroids, neuroimaging, and diagnosis of multiple sclerosis. The mean age at diagnosis was 6.5 ± 1.8 years (range, 3 to 9 years). Seventeen patients (85%) were female, and 13 patients (65%) exhibited bilateral diseases. Visual acuity had decreased to ≤20 / 200 in 16 of the 20 patients, and recovered to ≥20 / 40 in 16 of the 20 patients. The mean duration between the worst visual acuity and 20 / 40 was 2.30 ± 2.91 months. Intravenous corticosteroid treatment was performed in 15 patients and exerted a beneficial effect on the visual outcomes. Disc swelling was observed in 75.8% of the affected eyes. Multiple sclerosis was diagnosed in five patients with a mean follow-up period of 21.9 ± 20.3 months. The presence of lesions in brain magnetic resonance images was identified as the most significant factor with regards to the occurrence of multiple sclerosis. In children with optic neuritis, a profound decrease in initial visual acuity and rapid recovery of visual acuity were confirmed. Corticosteroid treatment resulted in a beneficial effect on visual outcomes, but had no effect on the risk of multiple sclerosis. © 2011 The Korean Ophthalmological SocietyY

Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study

Background/Aims Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. Methods We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. Results A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. Conclusions A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection