Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles -

Molecular hydrogen (H2) is clinically administered; however, in some hospitals, H2 is given to patients without consideration of its safe use. In the present study, we prepared convenient and safe devices for the drinking of super-saturated H2 water, for intravenous drip infusion of H2-rich saline, and for the inhalation of H2 gas. In order to provide useful information for researchers using these devices, the changes in H2 concentration were studied. Our experimental results should contribute to the advance of non-clinical and clinical research in H2 medicine.     

Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT

Journal of Gastroenterology - REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma...     

Ala601-Thr type dysplasminogenaemia genetically diagnosed in patients with retinochoroidal vascular disorders

Dysplasminogenaemia has been reported in patients with retinochoroidal vascular disorders. The precise genetic defects of these cases, however, remain unclear because of the limitations of conventional diagnostic techniques. In this study, three patients with these diseases were investigated at the DNA level for the first time to define the molecular bases of these disorders. Polymerase chain reaction–restriction fragment length polymorphism analysis revealed that all three cases carried the same Ala601-Thr mutation. This defect may also play a role in the pathogenesis of circulation disorders in small local vessels because of reduced fibrinolytic activity due to decreased functional plasminogen levels.     

Scintigraphic comparison of neorectal emptying between colonic J-pouch anastomosis and straight anastomosis after stapled low anterior resection

BACKGROUND AND AIMS. Colonic J-pouch anastomosis after low anterior resection of the rectum has been reported to be associated with an increased risk of evacuation difficulty. Using scintigraphy we compared neorectal emptying after stapled low anterior resection between colonic J-pouch anastomosis and straight anastomosis. PATIENTS AND METHODS. We studied 19 patients after colonic J-pouch anastomosis and 22 after straight anastomosis. After the introduction of an artificial stool containing (99m)Tc-DTPA into the neorectum sequential lateral gamma images were obtained. From the time activity curve of radioactivity in the whole pelvis the time taken to evacuate one-half of the introduced artificial stool ( t(1/2)) and the percentage of artificial stool evacuated in 1 min (Evac(1)) were calculated. Fourteen volunteers were also studied as the reference group. RESULTS. The t(1/2) was significantly longer and Evac(1) significantly lower in patients after low anterior resection than in the reference group. t(1/2) was significantly longer in the pouch group than in the straight group. Anastomotic height was significantly correlated with both t(1/2) and Evac(1). Neither t(1/2) nor Evac(1) was correlated with the severity of impaired defecatory function. CONCLUSION. Although neither of the two parameters of neorectal emptying was correlated with the severity of impaired defecatory function, less effective neorectal emptying in patients after colonic J-pouch anastomosis than in those after straight anastomosis may be a factor causing evacuation difficulty after colonic J-pouch anastomosis.     

Influence of contrast ultrasonography with perflutren lipid microspheres on microvessel injury.

Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0 ml/kg) or Levovist (300 mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0 ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting.     

Factors responsible for pathogenicity in chickens of a low-pathogenic H7N7 avian influenza virus isolated from a feral duck

Highly pathogenic avian influenza viruses have poly-basic amino acid sequences at the cleavage site in their hemagglutinin (HA). Although this poly-basic region is a prerequisite factor for pathogenicity in chickens, not much is known about additional factors responsible for the acquisition of pathogenicity of the duck influenza virus in chickens. Here, we introduced multiple basic amino acid residues into the HA cleavage site of the A/duck/Hokkaido/Vac-2/2004 (H7N7) strain of avian influenza virus, which has low pathogenicity in chickens; the resultant Vac2sub-P0 strain was not intravenously pathogenic in chickens. In contrast, the Vac2sub-P3 strain, which was recovered from three consecutive passages of Vac2sub-P0 in chicks, was intravenously pathogenic in chickens. Six amino acid substitutions were identified by comparison of the Vac2sub-P3 and Vac2sub-P0 genomic sequences: Lys123Glu in PB2, Asn16Asp in PB1, Glu227Gly and Ile388Thr in HA, Gly228Arg in M1, and Leu46Pro in M2. The results of intravenous inoculations of chickens with recombinant virus indicated that all six amino acid substitutions were required to varying degrees for Vac2sub-P3 pathogenicity, with Glu227Gly and Ile388Thr in HA being particularly essential. These results reveal the roles of additional viral factors in the acquisition of pathogenicity in addition to the previously characterized role of the poly-basic amino acid sequences at the HA cleavage site.     

Renal replacement therapy with a cytokine‐adsorbing hemofilter after neonatal open-heart surgery

Journal of Artificial Organs - Two neonates with right atrial isomerism, single right ventricle, common atrioventricular valve regurgitation, and obstructive extra-cardiac total anomalous pulmonary...     

Parp‐1 deficiency in ES cells promotes invasive and metastatic lesions accompanying induction of trophoblast giant cells during tumorigenesis in uterine environment

Embryonic stem (ES) cells deficient in poly(ADP‐ribose) polymerase‐1 (Parp‐1) develop into teratocarcinomas with the appearance of trophoblast giant cells (TGCs) when injected subcutaneously into nude mice. Because the uterus is one of the original organs in which germ cell tumors develop with induction of trophoblast lineage, here we investigated whether Parp‐1 deficiency in ES cells affects teratocarcinoma formation processes by grafting ES cells into the horns of uteri. Teratocarcinomas developed from both wild‐type (Parp‐1^+/+) and Parp‐1^?/? ES cells. The weights of the tumors derived from Parp‐1^?/? ES cells were lower than those of the tumors derived from Parp‐1^+/+ ES cells (P < 0.05). The Parp‐1^?/? tumors showed the appearance of TGCs. Notably, organ metastasis to the lung and liver was observed for the Parp‐1^?/? tumors, but not for the Parp‐1^+/+ tumors (P < 0.05). Invasions were more frequently observed with the Parp‐1^?/? tumors compared with the Parp‐1^+/+ tumors (P < 0.05). Since TGCs are known to have invasive properties, the appearance of TGCs may have supported the metastatic process. The present findings suggest that loss of Parp‐1 during teratocarcinoma formation might augment invasive and metastatic properties of the tumors in the uterine environment.