Decreased Immunoreactivities of the Chloride Transporters, KCC2 and NKCC1, in the Lateral Superior Olive Neurons of Kanamycin-treated Rats

ObjectivesFrom our previous study about the weak expressions of potassium-chloride (KCC2) and sodium-potassium-2 chloride (NKCC1) co-transporters in the lateral superior olive (LSO) in circling mice, we hypothesized that partially damaged cochlea of circling mice might be a cause of the weak expressions of KCC2 or NKCC1. To test this possibility, we reproduced the altered expressions of KCC2 and NKCC1 in the LSO of rats, whose cochleae were partially destroyed with kanamycin.MethodsRat pups were treated with kanamycin from postnatal (P)3 to P8 (700 mg/kg, subcutaneous injection, twice a day) and sacrificed for immunohistochemical analysis, scanning electron microscope (SEM) and auditory brain stem response.ResultsThe SEM study revealed partially missing hair cells in P9 rats treated with kanamycin, and the hearing threshold was elevated to 63.8±2.5 dB SPL (4 ears) at P16. Both KCC2 and NKCC1 immunoreactivities were more prominent in control rats on P16. On 9 paired slices, the mean densities of NKCC1 immunoreactivities were 118.0±1.0 (control) and 112.2±1.2 (kanamycin treated), whereas those of KCC2 were 115.7±1.5 (control) and 112.0±0.8 (kanamycin treated).ConclusionWe concluded that weak expressions of KCC2 and NKCC1 in circling mice were due to partial destruction of cochleae

Complexity of Atherosclerotic Coronary Artery Disease and Long-Term Outcomes in Patients With Unprotected Left Main Disease Treated With Drug-Eluting Stents or Coronary Artery Bypass Grafting

ObjectivesThe aim of this study was to compare treatment effects of drug-eluting stents (DES) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease according to the complexity of atherosclerotic disease burden.BackgroundLimited information is available on the relationships between the extent of coronary atherosclerosis and very long-term outcomes of surgical or percutaneous LMCA revascularization.MethodsA total of 1,146 patients with unprotected LMCA disease who received DES (n = 645) or underwent CABG (n = 501) were evaluated. The extent of atherosclerotic disease burden was measured using the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score; a low-risk score was defined as ≤22, an intermediate-risk score as 23 to 32, and a high-risk score as ≥33.ResultsAfter multivariate adjustment with the inverse-probability-of-treatment weighting method, the 5-year risks for death (6.1% for DES vs. 16.2% for CABG; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.21 to 1.28; p = 0.15) and the composite of death, Q-wave myocardial infarction, or stroke (6.4% vs. 16.2%; HR: 0.54; 95% CI: 0.22 to 1.34; p = 0.18) favored DES in patients with low-risk SYNTAX scores; in contrast, the 5-year risks for death (26.9% vs. 17.8%; HR: 1.46; 95% CI: 0.92 to 2.30; p = 0.11) and the composite outcome (27.6% vs. 19.5%; HR: 1.36; 95% CI: 0.87 to 2.12; p = 0.18) favored CABG in patients with high-risk SYNTAX scores (interaction p = 0.047 for death, interaction p = 0.08 for composite outcome). Patients undergoing CABG consistently had lower rates of target vessel revascularization.ConclusionsAccording to the complexity of concomitant coronary disease, there were differential treatment effects on long-term mortality in patients with unprotected LMCA disease who received DES or underwent CABG

The Possible Role of Nitric Oxide on Enteric Nerves-Mediated Relaxation of the Gastric Smooth Muscle of the Guinea Pig

The influence of the enteric nerves stimulation on the contractility of gastric circular muscle was studied in guinea pig stomachs. The enteric nerves were activated by electric field stimulation(EFS; 90 V, 1 rns, 32 Hz square pulses for 1 s), EFS produced initial transient contraction followed by relaxation and slow recovery. The initial contraction was sensitively blocked by treatment with atropine. The following relaxation still occurred in nonadrenergic noncholinergidNANC) state. EFSinduced relaxation was reduced by LG-nitro-L-arginine(L-NNA), a nitric oxide(NO) synthase inhibitor. The relaxation was restored from the suppressed state after the application of L-arginine(L-arg), a substrate of nitric oxide synthase. With conventional intracellular recording, slow wave and inhibitory junction potential(IJP) were recorded. L-NNA had no effect on IJP, while apamin blocked it. In conclusion, it is suggested that NO may playa major role in EFS-induced relaxation. The exact mechanism of this relaxation is unknown, but the relaxation does not result from the IJP induced by the activation of apamin-sensitive potassium channels

Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease 5-Year Outcomes of the PRECOMBAT Study

AbstractBackgroundIn a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.ObjectivesThis study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.MethodsWe randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.ResultsAt 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).ConclusionsDuring 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968

Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

<p>Abstract</p> <p>Background</p> <p>Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.</p> <p>Results</p> <p>Both protein and mRNA expression of <it>FoxP3</it>, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of <it>FoxP3 </it>in CD4⁺T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, <it>FoxP3 </it>expression is increased in CD4⁺T cells when co-cultured with DCs and concomitantly treated with resistin.</p> <p>Conclusion</p> <p>Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.</p

Hepatoid adenocarcinoma of the stomach: an unusual case of elevated alpha-fetoprotein with prior treatment for hepatocellular carcinoma

Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC). Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP) level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP