Clinical efficacy of probiotic Bifidobacterium longum for the treatment of symptoms of Japanese cedar pollen allergy in subjects evaluated in an environmental exposure unit.

BACKGROUND: Japanese cedar pollinosis (JCPsis) affects nearly one in six Japanese. Oral administration of Bifidobacterium longum BB536 has been shown to be effective in relieving JCPsis symptoms during the pollen season. METHODS: This double- two-way crossover study was designed to evaluate the efficacy of BB536 on reducing symptoms in JCPsis patients exposed to Japanese cedar pollen (JCP) in an environmental exposure unit (EEU) outside of the normal JCP season. After a 1-week run-in period, subjects (n=24) were randomly allocated to receive BB536 powder (approximately 5x1010) or placebo twice a day for 4 weeks. After a 2-week washout period, subjects were crossed over to another 4 weeks of intake. At the end of each intake period, subjects received controlled JCP exposure for 4 hours in the EEU. Symptoms were self-rated 30 minutes before and every 30 minutes during the exposures. From the first day of exposure through the next 5 successive days, participants self-rated their delayed symptoms and medication uses. Blood samples were taken before the exposures. The mean JCP levels for exposures were 6500 to 7000 grains/m3 air. RESULTS: In comparison with placebo, BB536 intake significantly reduced the ocular symptom scores during JCP exposures. Evaluating delayed symptoms after exposures indicated that scores for disruption of normal activities were significantly lower in the BB536 group compared with the placebo group. Prevalence of medication use was markedly reduced by BB536 intake. CONCLUSIONS: These results suggest the potential beneficial effect of BB536 in relieving symptoms of JCP allergy.     

Reduction of wear volume from ultrahigh molecular weight polyethylene knee components by the addition of vitamin E

Wear performance and debris‐size distribution of vitamin E (DL‐α tocopherol, VE)‐added ultrahigh molecular weight polyethylene (UHMWPE) was evaluated using a knee‐simulator test. VE was mixed with GUR 1050 UHMWPE powder at 0.3 wt%, and the tibial components of the knee joint were made by direct compression molding. The VE‐added UHMWPE showed consistently lower wear volume throughout the test. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:460–464, 2008     

Protein‐bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase‐1 mutation‐associated familial amyotrophic lateral sclerosis and its transgenic mouse model

Growing evidence documents oxidative stress involvement in ALS. We previously demonstrated accumulation of a protein‐bound form of the highly toxic lipid peroxidation product crotonaldehyde (CRA) in the spinal cord of sporadic ALS patients. In the present study, to the determine the role for CRA in the disease processes of superoxide dismutase‐1 (SOD1) mutation‐associated familial ALS (FALS), we performed immunohistochemical and semiquantitative cell count analyses of protein‐bound CRA (P‐CRA) in the spinal cord of SOD1‐mutated FALS and its transgenic mouse model. Immunohistochemical analysis revealed increased P‐CRA immunoreactivity in the spinal cord of the FALS patients and the transgenic mice compared to their respective controls. In the FALS patients, P‐CRA immunoreactivity was localized in almost all of the chromatolytic motor neurons, neurofilamentous conglomerates, spheroids, cordlike swollen axons, reactive astrocytes and microglia, and the surrounding neuropil in the affected areas represented by the anterior horns. In the transgenic mice, P‐CRA immunoreactivity was localized in only a few ventral horn glia in the presymptomatic stage, in almost all of the vacuolated motor neurons and cordlike swollen axons and some of the ventral horn reactive astrocytes and microglia in the onset stage, and in many of the ventral horn reactive astrocytes and microglia in the advanced stage. Cell count analysis on mouse spinal cord sections disclosed a statistically significant increase in the density of P‐CRA‐immunoreactive glia in the ventral horns of the young to old G93A mice compared to the age‐matched control mice. The present results indicate that enhanced CRA formation occurs in motor neurons and reactive glia in the spinal cord of SOD1‐mutated FALS and its transgenic mouse model as well as sporadic ALS, suggesting implications for CRA in the pathomechanism common to these forms of ALS.     

Asymptomatic Fungemia Due to Rhodotorula spp. Caused by a Subcutaneously Implanted Central Venous Port Catheter

A 66-year-old man was admitted to our hospital for gastrointestinal perforation. He had a history of surgery and chemotherapy for colorectal cancer and had a subcutaneously implanted central venous port catheter. After surgery for gastrointestinal tract perforation, he developed an intra-abdominal abscess, which was treated with broad-spectrum antimicrobial agents and improved. Following this improvement, Rhodotorula spp. was detected in a blood culture and at the catheter tip. He was asymptomatic despite having fungemia. His condition improved after the removal of the catheter and the administration of antifungal drugs. Fungemia due to Rhodotorula spp. is rare, and asymptomatic fungemia is even rarer.     

Chylomicron remnants stimulate release of interleukin-1beta by THP-1 cells

Recent findings suggest that the oxidative modification of low-density lipoproteins (LDL) and an increase in triglyceride-rich lipoprotein particles including chylomicron remnants contribute to the progression of atherosclerosis, as does the inflammatory response. We therefore examined whether and how these lipoproteins affected interleukin (IL)-1beta release and mRNA expression for IL-1beta and IL-18 in THP-1 cells, a human monocyte cell line. Chylomicron remnants increased IL-1beta release into the conditioned medium by THP-1 in a dose- and time-dependent manner. At concentrations up to 1 microg/ml, chylomicron remnants increased IL-1beta release by 4-fold compared with the control. Neither native LDL nor oxidized LDL (OxLDL) significantly increased IL-1beta release. Chylomicron remnants increased IL-1beta mRNA expression by 3 times. Native LDL or OxLDL did not increase IL-1beta mRNA, while neither these lipoproteins nor chylomicron remnants increased IL-18 mRNA. Chylomicron remnants also increased the activities of caspase-1 and nuclear factor (NF)-kappaB significantly, while native LDL or OxLDL did not. In conclusion, chylomicron remnants stimulated IL-1beta mRNA expression and IL-1beta protein production probably via caspase-1 and NF-kappaB activation in THP-1 cells.     

Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone: a population-based case-control study in Shanghai, China

Biliary tract cancer, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, is a rare but highly fatal malignancy. Obesity and gallstones, both related to insulin resistance, are linked to an elevated risk of biliary cancer. The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs), expressed in adipose tissue, play a key role in the regulation of obesity-related insulin sensitivity, thus genetic variants of these two receptor genes may be related to biliary cancer and stones. We examined the associations of seven single-nucleotide polymorphisms in the PPAR-gamma, PPAR-delta, RXR-alpha, RXR-beta and INS genes with biliary cancer and stones in a population-based case-control study in Shanghai, China. We included 237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater cancer cases, 895 stone cases and 786 population controls. Relative to individuals with the RXR-beta C51T (rs2076310) CC genotype, those having the TT genotype had a 1.6-fold risk for bile duct cancer [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 0.99-2.84], with a more pronounced association among men (OR = 2.30; 95% CI = 1.14-4.65; P interaction = 0.07). This marker was also associated with a higher risk of gallstones among subjects with a higher body mass index (BMI) (>or=23 kg/m(2)) (OR = 1.80; 95% CI = 1.09-2.94), although the interaction with BMI was not statistically significant (P interaction = 0.28). No association was found between other variants and biliary cancers and stones. Results from this population-based study suggest that certain genetic variants involved in the regulation of obesity-related insulin sensitivity may increase susceptibility to bile duct cancer and gallstones.     

Risk Factors Associated with Surgical Site Infection after Hepatectomy for Liver Disease

The incidence of postoperative SSI （surgical site infection） after hepatic resection has decreased gradually with the refinement of surgical techniques and perioperative management. However, postoperative SSI still develops in a few patients after hepatic resection, leading to increased medical costs, longer hospitalization and a reduced quality of life in the postoperative course. The purpose of this study was to analyze the risk factors of SSI and to assist in predicting the occurrence of SSI after hepatic resection. A retrospective analysis of 227 patients who underwent hepatic resection without biliary reconstruction for liver disease between January 2006 and December 2012 was performed. Patients were divided into two groups according the occurrence of SSI. The association between SSI and various clinical parameters was investigated. Nineteen patients developed SSI： 9 with superficial or deep SSI and 10 with organ/space SSI. In univariate analysis, preoperative platelets, aspartate aminotransferase and alanine aminotransferase concentrations, intraoperative blood loss, perioperative transfusion, procedure of skin closure, and postoperative bile leakage differed statistically between the two groups. Patients with SSI required significantly longer hospitalization than those without SSI. In multivariate analysis, conventional skin closure and postoperative bile leakage were the significant risk factors. It is important to prevent bile leakage to reduce postoperative SSI. Moreover, subcuticular suture for skin closure would be effective in preventing incisional SSI. Continuous efforts should be made to prevent SSI and further study is needed to develop additional new strategies for preventing SSI.     

Oxidative stress induces insulin resistance by activating the nuclear factor-κB pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase

Aims/hypothesis Oxidative stress is associated with diabetes, hypertension and atherosclerosis. Insulin resistance is implicated in the development of these disorders. We tested the hypothesis that oxidative stress induces insulin resistance in rats, and endeavoured to identify mechanisms linking the two.Methods Buthionine sulfoximine (BSO), an inhibitor of glutathione synthase, was administered to Sprague-Dawley rats and 3T3-L1 adipocytes. Glucose metabolism and insulin signalling both in vivo and in 3T3-L1 adipocytes were examined. In 3T3-L1 adipocytes, the effects of overexpression of a dominant negative mutant of inhibitory B (IB), one role of which is to block oxidative-stress-induced nuclear factor (NF)-B activation, were investigated.Results In rats given BSO for 2 weeks, the plasma lipid hydroperoxide level doubled, indicating increased oxidative stress. A hyperinsulinaemic-euglycaemic clamp study and a glucose transport assay using isolated muscle and adipocytes revealed insulin resistance in BSO-treated rats. BSO treatment also impaired insulin-induced glucose uptake and GLUT4 translocation in 3T3-L1 adipocytes. In BSO-treated rat muscle, adipose tissue and 3T3-L1 adipocytes, insulin-induced IRS-1 phosphorylation in the low-density microsome (LDM) fraction was specifically decreased, while that in whole cell lysates was not altered, and subsequent translocation of phosphatidylinositol (PI) 3-kinase from the cytosol and the LDM fraction was disrupted. BSO-induced impairments of insulin action and insulin signalling were reversed by overexpressing the dominant negative mutant of IB, thereby suppressing NF-B activation.Conclusions/interpretation Oxidative stress induces insulin resistance by impairing IRS-1 phosphorylation and PI 3-kinase activation in the LDM fraction, and NF-B activation is likely to be involved in this process.Abbreviations BSO buthionine sulfoximine - GMSA gel mobility shift assay - IB inhibitory B - IKK IB kinase - LDM low-density microsome - NF-B nuclear factor-B - PI phosphatidylinositol