Usefulness of urinary biomarkers for nephrotoxicity in cynomolgus monkeys treated with gentamicin, cisplatin, and puromycin aminonucleoside.

The objective of this study was to investigate the availability of novel urinary biomarkers (BMs) such as total protein, albumin, ß2-microglobulin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute nephrotoxicity in cynomolgus monkeys. Animals (total 9 males/3 groups) were administered gentamicin (GM) subcutaneously at 40 mg/kg for 7 days, cisplatin (CDDP) intravenously at 3 mg/kg once and puromycin aminonucleoside (PAN) intravenously at 20 mg/kg for 7 days. Two-hr urine on Days 0, 3, and 6, and 16-hr urine and blood on Days 1, 4, and 7 were collected. Novel urinary BMs and conventional clinical pathology parameters were evaluated in parallel to histopathological and electron microscopic examinations on the kidneys at termination. Urinary BMs and enzymes increased earlier than serum creatinine and blood urea nitrogen, particularly in 2-hr urine after dosing on Day 0, urinary albumin was increased in all groups and urinary NGAL with the highest magnitude of change rate among urinary BMs was observed in the GM and CDDP groups. Degeneration/necrosis and hyaline droplet of renal tubule, cellular cast and dilatation of renal tubule, and hypertrophy of podocytes were observed in the GEN, CDDP, and PAN groups, respectively. These results showed that the increases of urinary BMs reflected the agent-specific renal damages and these urinary BMs could be useful for the detection of segment-specific nephrotoxicity. Urinary albumin and NGAL are the most useful BMs to estimate glomerular and distal tubular damages, respectively, as well as proximal tubular damage in cynomolgus monkeys.

Effectiveness of trivalent influenza vaccine among children in two consecutive seasons in a community in Japan.

Influenza vaccination is considered the single most important medical intervention for the prevention of influenza. The dose of trivalent influenza vaccine in children was increased almost double since 2011/12 season in Japan. We estimated the influenza vaccine effectiveness for children 1-11 years of age using rapid test kits in Isahaya City, involving 28,884 children-years, over two consecutive influenza seasons (2011/12 and 2012/13). Children were divided into two groups, vaccinated and unvaccinated, according to their vaccination record, which was obtained from an influenza registration program organized by the Isahaya Medical Association for all pediatric facilities in the city. There were 14,562 and 14,282 children aged from 1-11 years in the city in 2011 and 2012 respectively. In the 2011/12 season, the overall vaccine effectiveness in children from 1-11 years of age, against influenza A and B were 23% [95% confidence interval (CI): 14%-31%] and 20% [95% CI: 8%-31%], respectively. In the 2012/13 season, vaccine effectiveness against influenza A and B was 13% (95% CI: 4%-20%) and 9% (95% CI: -4%-21%), respectively. The vaccine effectiveness was estimated using the rapid diagnosis test kits. Age-stratified estimation showed that vaccine effectiveness was superior in younger children over both seasons and for both virus types. In conclusion, the trivalent influenza vaccine has a significant protective effect for children 1-11 years of age against influenza A and B infection in the 2011/12 season and against influenza A infection in the 2012/13 season in a community in Japan.

[Juvenile nasopharyngeal angiofibroma--evaluation of the invasion of the pterygoid canal].

We operated on three patients with juvenile nasopharyngeal angiofibroma in the past 3 years. The endoscopic transnasal approach was utilized in all the cases, and in one case it was accompanied with a Caldwell-Luc procedure. All the tumors were located around the sphenopalatine foramen, but also had involved and enlarged the pterygoid canal. All the cases underwent preoperative selective embolization, but it was difficult to embolize the branch of the internal carotid artery. A partial resection of the middle turbinate facilitated the manipulation of the sphenopalatine foramen and the pterygoid canal. Endoscopic management of juvenile nasopharyngeal angiofibroma should be considered as a first-choice option for tumors at the early stage.

Dietary effect of pomegranate seed oil on immune function and lipid metabolism in mice.

OBJECTIVES: We evaluated the effects of dietary pomegranate seed oil (PSO), which contains high levels of punicic acid (9c, 11t, 13c-octadecatrienoic acid), on immune function and lipid metabolism in C57BL/6N mice. METHODS: Mice were fed experimental diets containing 0%, 0.12%, or 1.2% PSO for 3 wk. RESULTS: No significant differences were observed between growth patterns of the experimental groups. Splenocytes isolated from mice fed 0.12% or 1.2% PSO produced larger amounts of immunoglobulins G and M but not immunoglobulin A irrespective of stimulation with or without phorbol 12-myristate 13-acetate and the calcium ionophore A23187. Dietary PSO did not affect the percentages of B cells or CD4-positive or CD8-positive T cells in splenocytes. Levels of interleukin-4, interferon-gamma, and tumor necrosis factor-alpha production from splenocytes were comparable among all dietary groups. Analysis of serum lipid parameters showed significant increases in serum triacylglycerol and phospholipid levels but not in total cholesterol in the PSO groups. Serum, liver, epididymal, and perirenal adipose punicic acid levels were high with increases in dietary PSO level. However, punicic acid was not detected in splenocytes for any dietary group. Interestingly, 9c, 11t-conjugated linoleic acid level could be detected in serum, liver, and adipose tissues in mice fed the 0.12% or 1.2% PSO diet. CONCLUSIONS: These results suggest that PSO may enhance B-cell function in vivo.

Physiological difference between free and triglyceride-type conjugated linoleic acid on the immune function of C57BL/6N mice.

Previous studies have shown the physiological significance of dietary conjugated linoleic acid (CLA) in various experimental animals and in human beings. One of the important problems to better elucidate is the difference between triglyceride (TG) and free (FFA) dietary CLA. Here, using splenocytes, this study assesses how TG- and FFA-CLA modulate immunoglobulin and various cytokine productions. In this study, C57BL/6N mice were fed an experimental diet containing 0% CLA, 0.1 or 1% FFA-CLA, or 0.1 or 1% TG-CLA for 3 weeks. The production of immunoglobulin tended to be up-regulated by 1% FFA-CLA. As a result of protein array analysis using the supernatant from splenocytes cultured with no CLA, 1% FFA-CLA, and TG-CLA, some cytokine production was shown to be remarkably regulated by dietary FFA- and TG-CLA. A total of 32 cytokines were examined, and 11-14 produced cytokines that were 2-fold up-regulated as compared with control for FFA- or TG-CLA, respectively. Especially, the production of IL-9 and MCP-5 and other cytokines was remarkably up-regulated by both FFA- and TG-CLA. In addition, seven cytokines were 2-fold down-regulated by TG-CLA. These data show that there is a slight but significant difference between the functionalities of FFA- and TG-CLA.