Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis

To elucidate the associations between Lp(a) levels and coronary and aortic atherosclerosis, we performed aortic MRI in 143 patients undergoing coronary angiography. Severity of aortic atherosclerosis was represented as plaque scores. Of the 143 patients, 104 had coronary artery disease (CAD). Thoracic and abdominal aortic plaques were found in 89 and 131 patients. Lp(a) levels increased stepwise with the number of stenotic coronary vessels: 15.7 (CAD(-)), 21.2 (1-vessel), 21.4 (2-vessel), and 22.9 mg/dl (3-vessel) (P<0.05). For aortic atherosclerosis, 143 patients were divided into quartiles by plaque scores. Lp(a) did not differ among quartiles of thoracic plaques: 17.1, 19.0, 23.5, and 21.2 mg/dl (P=NS), whereas Lp(a) increased stepwise with quartiles of abdominal plaques: 17.1, 19.2, 19.1, and 24.0 mg/dl (P<0.05). Lp(a) was an independent factor for CAD and abdominal aortic plaques, but not thoracic plaques. Thus, Lp(a) levels were associated with aortic atherosclerosis, especially in abdominal aorta, as well as coronary atherosclerosis.     

Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation

Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glial-to-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function.     

New Surgical Approach to Large Splenorenal Shunt in Living Donor Liver Transplantation: Diversion of SMV and SPV Blood Flow

Introduction

The management of a large splenorenal shunt is important because it affects recipient outcome, particularly in living donor liver transplantation.

Methods

To manage large splenorenal shunts in living donor liver transplantation, we diverted superior mesenteric vein and splenic portal vein blood flow by ligation at the root of the splenic portal vein.

Result

This procedure was applied for five patients in whom superior mesenteric vein blood flow had been completely stolen by a splenorenal shunt preoperatively. Postoperative course was excellent in all cases.

Conclusion

This technique completely prevents morbidity related to large splenorenal shunts after living donor liver transplantation.     

Multicenter-evaluation of optimal cell density to determine antimicrobial susceptibility for Haemophilus influenzae by the automated RAISUS system when the early-harvested bacterial cells were used

The fully automated microbial system, RAISUS (Nissui Pharmaceutical, Tokyo, Japan) can provide antimicrobial susceptibility test results for the isolates of Haemophilus influenzae. It is known that viable cell concentrations (colony forming unit/ml) of H. influenzae significantly vary depending on the incubation period. For the rapid reporting of antimicrobial susceptibility test results, we evaluated optimal cell density when we prepared the cell suspension using the early-harvested (6 hour incubation) cells for RAISUS. A total of 180 clinical isolates, comprising of 33 ampicillin-susceptible isolates, 114 beta-lactamase negative but ampicillin-resistant isolates and 33 beta-lactamase positive and amoxicillin/clavulanic acid susceptible or -resistant isolates, were included. All the isolates were genetically defined according to the detection of TEM gene and specific mutation (s) in fts I gene. The isolates were incubated on chocolate agar plates for 6 hours, and then the cell suspensions were prepared and adjusted to 0.5, 0.25 and 0.125 McFarland standards through serially dilutions. The respective cell suspensions were tested by the RAISUS AST panels. The % agreements between RAISUS and Clinical and Laboratory Standards Institute standard microdilutions in ampicillin category interpretations were 66.7%(McFarland 0.5), 77.8% (McFarland 0.25) and 83.9%(McFarland 0.125). When the McFarland 0.125 cell suspensions were inoculated, the majority of discrep ant interpretations were minor errors (15.0%) and the occurrence of major error was 3.4%. There was no very major error throughout the study. Essential agreement in MIC determinations (with or within +/- 1 doubling dilution) for 11 beta-lactam antimicrobial agents tested improved to 95.2% by McFarland 0.125 when compared to 77.4% by McFarland 0.5. It was also demonstrated that the viable cell concentrations prepared from 6 hour incubation cultures were 2.5 to 6.5 times higher than those from 22 hour-incubations. With these results, it can be concluded that the early harvested cell suspension of H. influenzae is applicable to RAISUS antimicrobial susceptibility test with lower cell density (McFarland 0.125). With this adjustment, the antimicrobial susceptibility test for H. influenzae will be completed by RAISUS within 26 hours after primary isolation.     

Combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1′-oxybis-, tetrapropylene derivs. in rats

We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1′-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000?mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42–53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods. Increases in prothrombin time and activated partial thromboplastin time values were observed only in males at 200 and 1000?mg/kg/day. Hypertrophy of centrilobular hepatocytes was observed with increased liver weight in both sexes at 200 and 1000?mg/kg/day, but there was no histologic evidence of hepatotoxicity. Diffuse hypertrophy of follicular cells in thyroid glands was observed in females at 200?mg/kg/day and in both sexes at 1000?mg/kg/day, with an increased blood cholesterol level in females at 1000?mg/kg/day. The conception index was decreased for females at 1000?mg/kg/day; and no abnormalities were detected in the reproductive indices of implantation, delivery, or pups’ condition, although a slight increase in the pups’ body weight was noted at birth. Our data indicate a no-observed-adverse-effect level of 40?mg/kg/day for repeated-dose toxicity on the basis of the prolongation of blood coagulating time, and of 200?mg/kg/day for reproductive/developmental toxicity on the basis of the decreased conception index.