Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-κB and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-κB was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-κB translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-α in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug

Efficacy of early immunomodulator therapy on the outcomes of Crohn’s disease

BACKGROUND: The natural course of Crohn’s disease (CD), with continuing relapses and remissions, leads to irreversible intestinal damage. Early adoption of immunomodulator therapy has been proposed in order to address this; however, it is still uncertain whether early immunomodulator therapy could affect the natural course of the disease in real practice. We evaluated the efficacy of such therapy on the prognosis of newly diagnosed patients with CD. METHODS: This retrospective study included 168 patients who were newly diagnosed with CD and who started treatment at Severance Hospital, Seoul, Korea between January 2006 and March 2013. The short- and long-term outcomes were compared between patients treated with early immunomodulator therapy and those treated with conventional therapy. RESULTS: A Kaplan-Meier analysis identified that administration of immunomodulators within 6 months after diagnosis of CD was superior to conventional therapy in terms of clinical remission and corticosteroid-free remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related adverse events were more frequent in the early immunomodulator therapy group than in the conventional therapy group P=0.029). CONCLUSIONS: Early immunomodulator therapy was more effective than conventional therapy in inducing remission, but not in preventing relapse. Baseline high CRP level was a significant indicator of relapse

Little Response of Cerebral Metastasis from Hepatocellular Carcinoma to Any Treatments

Objective : We retrospectively evaluated the survival outcome of patients with brain metastasis from hepatocellular carcinoma (HCC). Methods : Between 1991 and 2007, a total of 20 patients were diagnosed as having brain metastasis from HCC. The mean age of the patients was 55 +/- 13 years, and 17(85.0%) were men. Seventeen (85.0%) patients had already extracranial metastases. The median time from diagnosis of HCC to brain metastasis was 18.5 months. Fourteen (70.0%) patients had stroke-like presentation due to intracerebral hemorrhage (ICH). Ten (50.0%) patients had single or solitary brain metastasis. Among a total of 34 brain lesions, 31 (91.2%) lesions had the hemorrhagic components. Results : The median survival time was 8 weeks (95% Cl, 5.08-10.92), and the actuarial survival rates were 85.0%, 45.0%, 22.5%, and 8.4% at 4, 12, 24, and 54 weeks. Age < 60 years, treatment of the primary and/or extracranial lesions, and recurrent ICH were the possible prognostic factors (p = 0.044, p < 0.001, and p = 0.111, respectively). The median progression-free survival (PFS) time was 3 months (95% Cl, 0.95-5.05). Conclusion : The overall survival of the patients with brain metastasis from HCC was very poor with median survival time being only 8 weeks. However, the younger patients less than 60 years and/or no extracranial metastases seem to be a positive prognostic factor.Choi HJ, 2009, J NEURO-ONCOL, V91, P307, DOI 10.1007/s11060-008-9713-3Kim SR, 2006, WORLD J GASTROENTERO, V12, P6727Seinfeld J, 2006, J NEURO-ONCOL, V76, P93, DOI 10.1007/s11060-005-4175-3Cho DC, 2005, J CLIN NEUROSCI, V12, P699, DOI 10.1016/j.jocn.2004.08.026Chang L, 2004, SURG NEUROL, V62, P172, DOI 10.1016/j.surneu.2003.10.002Del Ben M, 2003, J EXP CLIN CANC RES, V22, P641El-Serag HB, 2002, J CLIN GASTROENTEROL, V35, pS72SALVATI M, 2002, J NEUROSURG SCI, V46, P77McIver JI, 2001, NEUROSURGERY, V49, P447Hayashi K, 2000, SURG NEUROL, V53, P379El-Serag HB, 1999, NEW ENGL J MED, V340, P745Peres MFP, 1998, ARQ NEURO-PSIQUIAT, V56, P658Deuffic S, 1998, LANCET, V351, P214Kim M, 1998, J NEURO-ONCOL, V36, P85TaylorRobinson SD, 1997, LANCET, V350, P1142Gaspar L, 1997, INT J RADIAT ONCOL, V37, P745LUCEY MR, 1997, LIVER TRANSPLANT SUR, V3, P628Murakami K, 1996, NEURORADIOLOGY, V38, pS31PATCHELL RA, 1990, NEW ENGL J MED, V322, P494OTSUKA S, 1987, NEUROL MED CHIR TOKY, V27, P654OKEN MM, 1982, AM J CLIN ONCOL-CANC, V5, P649PUGH RNH, 1973, BRIT J SURG, V60, P646

Phenotyping of rice in salt stress environment using high-throughput infrared imaging

Phenotyping of rice (Oryza sativa L. cv. Donggin) in salt stress environment using infrared imaging was conducted. Results were correlated with the most frequently used physiological parameters such as stomatal conductance, relative water content and photosynthetic parameters. It was observed that stomatal conductance (R2 = –0.618) and relative water content (R2 = –0.852) were significantly negatively correlated with average plant temperature (thermal images), while dark-adapted quantum yield (Fv/Fm, R2 = –0.325) and performance index (R2 = –0.315) were not consistent with plant temperature. Advantages of infrared thermography and utilization of this technology for the selection of stress tolerance physiotypes are discussed in detail

Introduction of Transmembrane Inner Ear (tmie) Gene Can Recover the Hearing Impairment and Abnormal Behavior in the Circling Mouse

The spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing the causative gene, transmembrane inner ear (tmie), for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir -tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir -tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse

Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures

PurposeThe aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM.MethodsA retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day.ResultsSeventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults.ConclusionLEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring

Efficacy of Antibiotics Sprayed into Surgical Site for Prevention of the Contamination in the Spinal Surgery

Study DesignRetrospective study.PurposeTo evaluate the effect of intraoperative wound application of vancomycin on preventing surgical wound contamination during instrumented lumbar spinal surgery.Overview of LiteraturePostoperative infection is the one of the most devastating complications of lumbar surgery. There are a few reports showing the benefits of intraoperative wound application of vancomycin during spinal surgery. However, there is no report about the effectiveness of local vancomycin instillation in prevention of surgical wound contamination.MethodsEighty-six patients underwent instrumented lumbar spinal surgery. Mean patient age was 65.19 years (range, 23-83 years). There were 67 females and 19 males. During surgery, vancomycin powder was applied into the surgical site before closure in 43 patients (antibiotic group) and vancomycin powder was not applied into the surgical site before closure in 43 patients (control group). The tip of the surgical drain was cultured to evaluate surgical wound contamination. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured on the first, third, seventh, and fourteenth day after the operation.ResultsWe found two patients with a positive culture from the tip of surgical drains in the antibiotic group, and one patient with a positive culture from the tip of the surgical drain in the control group. Postoperative ESR and CRP levels did not show significant differences between the two groups. On the third postoperative day, ESR in patients of the antibiotic group was more significantly decreased than that in patients of the control group, while CRP level did not show a significant difference between the two groups.ConclusionsThere was no evidence to suggest that intraoperative vancomycin application is effective in decreasing the risk of postoperative wound infection after instrumented posterior lumbar fusion surgery

HIGH CROSSOVER RATE1 encodes PROTEIN PHOSPHATASE X1 and restricts meiotic crossovers in Arabidopsis.

Meiotic crossovers are tightly restricted in most eukaryotes, despite an excess of initiating DNA double-strand breaks. The majority of plant crossovers are dependent on class I interfering repair, with a minority formed via the class II pathway. Class II repair is limited by anti-recombination pathways; however, similar pathways repressing class I crossovers have not been identified. Here, we performed a forward genetic screen in Arabidopsis using fluorescent crossover reporters to identify mutants with increased or decreased recombination frequency. We identified HIGH CROSSOVER RATE1 (HCR1) as repressing crossovers and encoding PROTEIN PHOSPHATASE X1. Genome-wide analysis showed that hcr1 crossovers are increased in the distal chromosome arms. MLH1 foci significantly increase in hcr1 and crossover interference decreases, demonstrating an effect on class I repair. Consistently, yeast two-hybrid and in planta assays show interaction between HCR1 and class I proteins, including HEI10, PTD, MSH5 and MLH1. We propose that HCR1 plays a major role in opposition to pro-recombination kinases to restrict crossovers in Arabidopsis.Marie Curie International Training Network COMREC European Research Council (ERC) National Research Foundation of Korea Suh Kyungbae Foundatio