The Effect of Clonidine Pretreatment on Epidural Resiniferatoxin in a Neuropathic Pain Rat Model

Resiniferatoxin (RTX) is an ultrapotent synthetic TRPV1 (transient receptor potential vanilloid subtype 1) agonist with significant initial transient hyperalgesia followed by a prolonged analgesic effect in response to thermal stimulus. Using a rat model of neuropathic pain, we evaluated the effect of pretreatment with clonidine－which has been shown to relieve intradermal capsaicin-induced hyperalgesia－on the initial hyperalgesic response and the thermal analgesic property of RTX. Thirty-six male rats were divided into 6 treatment groups (n＝6 each):RTX 500ng, RTX 1μg, clonidine 20μg (Cl), Cl＋RTX 500ng, Cl＋RTX 1μg, or normal saline 20μL (control). We evaluated the short-term (180min) and long-term (20 days) analgesic effects of RTX after thermal stimulation and mechanical stimulation. RTX had significant initial transient hyperalgesia followed by a prolonged analgesic effect in response to the thermal stimulus, but the RTX 500ng and RTX 1μg groups showed no initial short-term thermal hyperalgesic responses when pretreated with clonidine. The Cl＋RTX 1μg ratsʼ behavior scores indicated that they were more calm and comfortable compared to the RTX 1μg rats. Even though we cannot precisely confirm that pretreatment with clonidine potentiates or adds to the analgesic effect of RTX, clonidine pretreatment with epidural RTX eliminated the initial RTX-associated hyperalgesic response and systemic toxicity in this neuropathic pain rat model

Proteomic analysis of pregnancy-related proteins from pig uterus endometrium during pregnancy

Many important molecular events associated with implantation and development occur within the female reproductive tract, especially within the uterus endometrium, during pregnancy periods. The endometrium includes the mucosal lining of the uterus, which provides a suitable site for implantation and development of a fertilized egg and fetus. To date, the molecular cascades in the uterus endometrium during pregnancy periods in pigs have not been elucidated fully. In this study, we compared the functional regulated proteins in the endometrium during pregnancy periods with those in non-pregnant conditions and investigated changes in expression patterns during pregnancy (days 40, 70, and 93) using two-dimensional gel electrophoresis (2-DE) and western blotting. The functional regulated proteins were identified and discovered from differentially expressed proteins in the uterus endometrium during pregnancy. We discovered 820 protein spots in a proteomic analysis of uterus endometrium tissues with 2-DE gels. We identified 63 of the 98 proteins regulated differentially among non-pregnant and pregnant tissues (matched and unmatched spots). Interestingly, 10 of these 63 proteins are development-, cytoskeleton- and chaperon-related proteins such as transferrin, protein DJ-1, transgelin, galectin-1, septin 2, stathmin 1, cofilin 1, fascin 1, heat shock protein (HSP) 90β and HSP 27. The specific expression patterns of these proteins in the endometrium during pregnancy were confirmed by western blotting. Our results suggest that the expressions of these genes involved in endometrium function and endometrium development from early to late gestation are associated with the regulation of endometrium development for maintaining pregnancy

Transmission of Seasonal Outbreak of Childhood Enteroviral Aseptic Meningitis and Hand-foot-mouth Disease

This study was conducted to evaluate the modes of transmission of aseptic meningitis (AM) and hand-foot-mouth disease (HFMD) using a case-control and a case-crossover design. We recruited 205 childhood AM and 116 HFMD cases and 170 non-enteroviral disease controls from three general hospitals in Gyeongju, Pohang, and Seoul between May and August in both 2002 and 2003. For the case-crossover design, we established the hazard and non-hazard periods as week one and week four before admission, respectively. In the case-control design, drinking water that had not been boiled, not using a water purifier, changes in water quality, and contact with AM patients were significantly associated with the risk of AM (odds ratio [OR]=2.8, 2.9, 4.6, and 10.9, respectively), while drinking water that had not been boiled, having a non-water closet toilet, changes in water quality, and contact with HFMD patients were associated with risk of HFMD (OR=3.3, 2.8, 6.9, and 5.0, respectively). In the case-crossover design, many life-style variables such as contact with AM or HFMD patients, visiting a hospital, changes in water quality, presence of a skin wound, eating out, and going shopping were significantly associated with the risk of AM (OR=18.0, 7.0, 8.0, 2.2, 22.3, and 3.0, respectively) and HFMD (OR=9.0, 37.0, 11.0, 12.0, 37.0, and 5.0, respectively). Our findings suggest that person-to-person contact and contaminated water could be the principal modes of transmission of AM and HFMD

Small anisotropy of the lower critical field and s±s_\pm-wave two-gap feature in single crystal LiFeAs

The in- and out-of-plane lower critical fields and magnetic penetration depths for LiFeAs were examined. The anisotropy ratio $\gamma_{H_{c1}}(0)$ is smaller than the expected theoretical value, and increased slightly with increasing temperature from 0.6$T_c$ to $T_c$. This small degree of anisotropy was numerically confirmed by considering electron correlation effect. The temperature dependence of the penetration depths followed a power law($\sim$$T^n$) below 0.3$T_c$, with $n$$>$3.5 for both $\lambda_{ab}$ and $\lambda_c$. Based on theoretical studies of iron-based superconductors, these results suggest that the superconductivity of LiFeAs can be represented by an extended $s_\pm$-wave due to weak impurity scattering effect. And the magnitudes of the two gaps were also evaluted by fitting the superfluid density for both the in- and out-of-plane to the two-gap model. The estimated values for the two gaps are consistent with the results of angle resolved photoemission spectroscopy and specific heat experiments.Comment: 10 pages, 5 figure

Impact of insulin therapy on the mortality of acute heart failure patients with diabetes mellitus

Background Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients. Methods A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups. Results DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21–1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14–1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c < 7.0 %) receiving insulin, whereas there was no significant association in patients with poor glycemic control (HbA1c ≥ 7.0%). Conclusions Insulin therapy was found to be associated with increased mortality compared to OHAs. The insulin therapy was harmful especially in patients with low HbA1c levels which may suggest the necessity of specific management strategies and blood sugar targets when using insulin in patients with HF.This study was supported by the Research of Korea Centers for Disease Control and Prevention (2010-E63003-00, 2011-E63002-00, 2012-E63005-00, 2013E63003-00, 2013-E63003-01, 2013-E63003-02, and 2016-ER6303-00

Acetic acid-indigo carmine chromoendoscopy for delineating early gastric cancers: its usefulness according to histological type

<p>Abstract</p> <p>Background</p> <p>Endoscopic treatments, such as endoscopic submucosal dissection (ESD) and laparoscopic gastrectomy, are increasingly used to treat a subset of patients with early gastric cancer (EGC). To achieve successful outcomes, it is very important to accurately determine the lateral extent of the tumor. Therefore, we investigated the diagnostic performance of chromoendoscopy using indigo carmine dye added to acetic acid (AI chromoendoscopy) in delineating differentiated or undifferentiated adenocarcinomas in patients with EGC.</p> <p>Methods</p> <p>We prospectively included 151 lesions of 141 patients that had an endoscopic diagnosis of EGC. All the lesions were examined by conventional endoscopy and AI chromoendoscopy before ESD or laparoscopic gastrectomy. The border clarification between the lesion and the normal mucosa was classified as distinct or indistinct before and after AI chromoendoscopy.</p> <p>Results</p> <p>The borders of the lesions were distinct in 66.9% (101/151) with conventional endoscopy and in 84.1% (127/151) with AI chromoendoscopy (<it>P </it>< 0.001). Compared with conventional endoscopy, AI chromoendoscopy clarified the border in a significantly higher percentage of differentiated adenocarcinomas (74/108 [68.5%] vs 97/108 [89.8%], respectively, <it>P </it>< 0.001). However, the border clarification rate for undifferentiated adenocarcinomas did not differ between conventional endoscopy and AI chromoendoscopy (27/43 [62.8%] vs 30/43 [70.0%], respectively, <it>P </it>= 0.494).</p> <p>Conclusions</p> <p>AI chromoendoscopy is useful in determining the lateral extent of EGCs. However, its usefulness is reduced in undifferentiated adenocarcinomas.</p

Neogenin expression may be inversely correlated to the tumorigenicity of human breast cancer

BACKGROUND: Neogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated. METHODS: To compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong) by a single well-trained blinded pathologist and statistically analyzed. RESULTS: The nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8) of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46) of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p < 0.001). CONCLUSION: Neogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation