All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 ± 119 IU/L and 72.7%) compared with the control group (713 ± 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-α (TNF-α) and superoxide anions produced by activated macrophages. Serum levels of TNF-α 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5 ± 7.0 ng/mL) as compared with the control group (105.2 ± 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.     

Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.     

Malignant mesothelioma of testicular tunica vaginalis

We report here a case with malignant mesothelioma of testicular tunica vaginalis. An 81-year-old Japanese man with left hydrocele was referred for operation. When hydrocelectomy was performed, a thick wall of tunica vaginalis without malignancy was observed. Seven months after hydrocelectomy, a hard irregular mass was noticed in the left scrotum, therefore inguinal orchiectomy was performed. Pathologically, the mass showed severe atypia and mitosis. The diagnosis of malignant mesothelioma was made. He refused any adjuvant treatment and died 1 year later from multiple metastases to the paraaortic lymph nodes and lumbar supine.     

A Novel Missense Mutation Causing a G487R Substitution in the S2–S3 Loop of Human ether‐à‐go‐go‐Related Gene Channel

hERG(G487R) Channel . Introduction: Mutations of human ether‐à‐go‐go‐related gene (hERG), which encodes a cardiac K⁺ channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2–S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function. Methods and Results: We made whole‐cell voltage‐clamp recordings from HEK‐293T cells transfected with wild‐type hERG [hERG(WT)], hERG(G487R), or both. We measured hERG channel‐mediated current as the “tail” of a depolarization‐elicited current. The current density of the tail current and its voltage‐ and time‐dependences were not different among all the cell groups. The time‐courses of deactivation, inactivation, and recovery from inactivation and their voltage‐dependences were not different among all the cell groups. Furthermore, we performed immunocytochemical analysis using an anti‐hERG subunit antibody. The ratio of the immunoreactivity of the plasma membrane to that of the cytoplasm was not different between cells transfected with hERG(WT), hERG(G487R), or both. Conclusion: hERG(G487R) can produce functional channels with normal gating kinetics and cell‐surface expression efficiency with or without the aid of hERG(WT). Therefore, neither the heterozygous nor homozygous inheritance of hERG(G487R) is thought to cause severe cardiac disorders. hERG(G487R) would be a candidate for a rare variant or polymorphism of hERG with an amino acid substitution in the unusual region of the channel subunit. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1246–1253, November 2012)     

Pharmacological Properties of Pteleprenine,a Quinoline Alkaloid Extracted from Orixa japonica,on Guinea-pig Ileum and Canine Left Atrium

We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium. Although pteleprenine (0·1–1 μM) had no effect on the contraction of the ileum induced by acetylcholine at 10 μM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0·1–10 μM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 μM From Schild analysis the pA₂ of pteleprenine on the guinea-pig ileum was found to be 6-6. The contraction of the ileum induced by 10 μM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine. receptors, was concentration-dependently suppressed by 10 nM-10 μM pteleprenine. In contrast, 0.1–10 μM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.     

Percutaneous cryoablation of renal cell carcinoma guided by horizontal open magnetic resonance imaging

BACKGROUND: Cryoablation is a treatment option for some patients with small exophytic lesions of the kidney. The purpose of this study is to determine the feasibility, safety, and intermediate-term treatment outcome of percutaneous cryoablation of renal cell carcinoma guided by horizontal open magnetic resonance imaging (MRI). METHODS: We prospectively used cryoablation to treat 13 patients with radiographically confirmed enhancing small, solid renal tumors (< or =4.8 cm). An argon gas-based cryoablation system was used. One to four cryoprobes with 2 or 3-mm diameters were placed percutaneously into the tumor under local anaesthesia and MRI guidance. Ice ball dimensions were monitored by 2-D MR images. Double freeze-thaw cycles were conducted throughout the procedure. After successful cryoablation, patients were followed on a regular basis to evaluate the treatment's clinical outcome. RESULTS: Median follow up from time of procedure is 35 months (range, 28-42). In all cases the entire procedure was accomplished without significant morbidity or complications. A mild retroperitoneal hematoma, which subsided spontaneously, was noted in one patient. Follow-up dynamic computed tomography (CT) at 3 months after operation confirmed the absence of enhancement in resolved tumor masses for 11 of 13 cases. None of these 11 patients had clinical evidence of recurrent disease at last follow up. The remaining two patients had lesions with some enhanced areas. Subsequent partial nephrectomy histologically confirmed the presence of vital tumor in, respectively, the center and the periphery of the residual masses. One of these patients developed multiple lung and ipsilateral adrenal metastases 13 months after surgical resection. CONCLUSIONS: Percutaneous cryoablation of small renal cell carcinomas under horizontal open MRI guidance appears to be safe and feasible. An intermediate-term follow up continues to demonstrate efficacy in most patients; however, a few patients experience incomplete ablation with risk of treatment failure. The ideal candidates for this procedure still need to be determined in longer follow up with diligent observation.