The germ-free mice monocolonization with Bacteroides fragilis improves azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer.

Objective: Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated colorectal cancer (CAC). Previous studies have indicated that the composition of gut microflora may be involved in CAC induction and progress. Bacteroides fragilis (BF) is a Gram-negative anaerobe belonging to colonic symbiotic bacteria of the host. This study was aimed to investigate the protective role of BF in a colorectal cancer (CRC) model induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in germ-free (GF) mice. Materials and methods: Total 22 GF mice were divided into two groups: GF and BF group. Half of the GF mice were colonized with BF for 28 days before CRC induction by AOM/DSS. Results: BF colonization increased animal survival (100%). Cecum weight and cecum/body weight ratio significantly decreased in BF/AOM/DSS group. Interestingly, there was a significant decrease in tumor number and tumor incidence in the BF/AOM/DSS group as compared to the GF/AOM/DSS group. The adenocarcinoma/adenoma incidence and histologic score were also decreased in the BF/AOM/DSS group. In addition, immunohistochemistry staining found decreased numbers of cell proliferation (PCNA) and inflammatory cell (granulocytes) infiltration in the colon mucosa of the BF group. The ß-catenin staining in the BF/AOM/DSS group had fewer and weaker positive signal expressions. Taking together, the BF colonization significantly ameliorated AOM/DSS-induced CRC by suppressing the activity of cell proliferation-related molecules and reducing the number of inflammatory cells. Conclusions: Symbiotic BF may play a pivotal role in maintaining the gastrointestinal immunophysiologic balance and regulating anti-tumorigenesis responses.

Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components.

BACKGROUND: The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. METHODS: One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. RESULTS: Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4(+) and CD8(+) T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4 T1 mammary tumors and prolonging survival in test mice. Only HSP70, but not CRT or HMGB1, is effective for the suppression of both granulocytic and monocytic MDSC populations in vivo. Both HSP70 and HMGB1, but not CRT, are essential in activating the expression of three key ICD molecules-associated receptors on test DCs. Each of the three test ICD proteins can exhibit a distinguishable pattern in stimulating the expression of four key chemokines in test DCs. CONCLUSION: Our findings on the differential roles or effect of various ICD components in activating vaccinated DCs may help formulate new strategies for future cancer vaccine designs.

FLG P478S polymorphisms and environmental risk factors for the atopic march in Taiwanese children: a prospective cohort study.

BACKGROUND: Little is known about the role of genetic and environmental modifiers in atopic march. OBJECTIVE: To investigate the effects of filaggrin (FLG) P478S polymorphisms and environmental factors on the risk of asthma in a cohort of children with atopic dermatitis (AD). METHODS: In 2010, 3,246 children from Childhood Environment and Allergic Diseases Cohort Study cohort were recruited. There were 485 children with AD who were invited for further clinical evaluation. Environmental exposures and skin prick tests for allergens were collected at 3 years of age and the development of asthma was determined at 6 years. Multivariate logistic regressions were performed to estimate the association between genetic and environmental factors and the development asthma in children with AD. RESULTS: Of 397 children with AD who completed the follow-up, 97 developed asthma. After controlling for potential confounders, only mite sensitizations (odds ratio 1.89, 95% confidence interval 1.10-3.25) and the FLG TT genotype (odds ratio 2.26, 95% confidence interval 1.33-3.84) were significantly associated with the development of asthma in children with AD. Mite sensitizations and FLG variants had a synergistic effect on the development of asthma. When children with FLG variants were exposed to mite, the risk for asthma was compounded compared with those with FLG variants without mite exposure (odds ratio 3.58, 95% confidence interval 1.81-7.08). CONCLUSION: Mite sensitization and the FLG TT genotype couldt be associated with the development of atopic march.

Heatstroke Effect on Brain Heme Oxygenase-1 in Rats.

Exposure to high environmental temperature leading to increased core body temperature above 40°C and central nervous system abnormalities such as convulsions, delirium, or coma is defined as heat stroke. Studies in humans and animals indicate that the heat shock responses of the host contribute to multiple organ injury and death during heat stroke. Heme oxygenase-1 (HO-1)-a stress-responsive enzyme that catabolizes heme into iron, carbon monoxide, and biliverdin-has an important role in the neuroprotective mechanism against ischemic stroke. Here, we investigated the role of endogenous HO-1 in heat-induced brain damage in rats. RT-PCR results revealed that levels of HO-1 mRNA peaked at 0 h after heat exposure and immunoblot analysis revealed that the maximal protein expression occurred at 1 h post-heat exposure. Subsequently, we detected the HO-1 expression in the cortical brain cells and revealed the neuronal cell morphology. In conclusion, HO-1 is a potent protective molecule against heat-induced brain damage. Manipulation of HO-1 may provide a potential therapeutic approach for heat-related diseases.

Effects of Lactobacillus salivarius ssp. salicinius SA-03 Supplementation on Reversing Phthalate-Induced Asthma in Mice.

Probiotics may protect against asthma. We want to investigate whether probiotics can reverse the adverse effects of phthalate exposure on asthma. We selected the female offspring of BALB/c mice, born from pregnant female mice fed with diethylhexyl phthalate (DEHP). They were continuously administrated DEHP and Lactobacillus salivarius ssp. salicinius SA-03 when they were 5 weeks old, and ovalbumin (OVA) for asthma induction started at 6 weeks for 32 days. The mice were divided into four groups (n = 6/group): 1. control group (C), 2. OVA/DEHP group (OD), 3. OVA/DEHP/probiotics low-dose group (ODP-1X), and OVA/DEHP/probiotics high-dose group (ODP-5X). We found that the administration of probiotics significantly reduced the asthma severity of the mice, as well as serum IgE and IL-5. In the ODP-5X group, the proportion of CD4+ cells in the lung was reduced, whereas IL-10 in serum and CD8+ cells in BALF were increased. In histopathology, the ODP group showed reduced infiltration of inflammatory cells, bronchial epithelial cell hyperplasia, and tracheal mucus secretion. These results might indicate that high-dose probiotics may affect anti-inflammatory cytokines and reduce asthma-relative indicators. The above results may provide evidence that high-dose probiotics supplementation might play a modulating role in DEHP causes of allergic asthma in the pediatric animal model.

Haemophilus influenzae type b combination vaccines and atopic disorders: a prospective cohort study.

BACKGROUND/PURPOSE: Epidemiologic evidence for an association between vaccinations and atopy development is inconsistent. We evaluated the influence of Haemophilus influenzae type b (Hib) combination vaccines in 6-month-old infants on the prevalence of atopic disorders in 18-month-old children. METHODS: We used multistage, stratified systematic sampling to recruit 24,200 mother-newborn pairs from the Taiwan national birth registration in 2005. Vaccination status was ascertained through official vaccine cards, while risk factors for atopic disorders were gathered by questionnaires at 6 months of age. Information about development of atopic dermatitis (AD) and recurrent wheezing was collected at 18 months of age. The relationship between atopic disorders and Hib combination vaccines, diphtheria-pertussis-tetanus-Hib and oral poliomyelitis vaccines (DPT-Hib&OPV) and DPT-Hib-inactivated poliomyelitis vaccines (DPT-Hib-IPV), were estimated by multiple logistic regression. RESULTS: A total of 19,968 children completed the follow-up and participated in the study. AD was noted in 1584 (7.9%) infants while recurrent wheezing was found in 1220 (6.1%) infants. The adjusted odds ratios (ORs) (95% CI) for the development of AD in the DPT-Hib&OPV and DPT-Hib-IPV vaccination groups were given as 1.38 (1.15-1.65) and 1.49 (1.29-1.72), compared to those without Hib vaccination (DTP&OPV vaccination). However, the association between DPT-Hib&OPV and DPT-Hib-IPV vaccinations and recurrent wheezing failed to reach statistical significance. CONCLUSION: There is a potential risk for AD after receiving Hib combination vaccines. Hib vaccination is important to the public health, and therefore the observation requires further investigations.

Gene transfer of IGF1 attenuates hepatocellular apoptosis after bile duct ligation.

BACKGROUND: Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis, causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. Insulin-like growth factor 1 (IGF1) acts in an autocrine and paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3 K)/Akt, the downstream glycogen synthase kinase 3ß (GSK3ß), and anti-apoptotic pathways. This study investigated whether gene transfer of IGF1 could attenuate hepatocellular injury after bile duct ligation in rats. MATERIALS AND METHODS: Experiments were performed in 80 male Sprague-Dawley rats. Thirty minutes after bile duct ligation, hydrodynamics-based gene transfection with IGF1 plasmid via rapid tail vein injection. The rats were randomly divided into the following four groups: sham operated; BDL treated with pCMV-IGF1 gene; BDL treated with vehicle for pCMV-LacZ gene; and BDL only. RESULTS: IGF1 expression in liver after a single administration of IGF-1 plasmid was demonstrated. Liver function index, including serum alanine aminotransferase and aspartate aminotransferase, were significantly reduced in IGF1 gene transfer rats. We determined the mechanism of IGF1 gene transfer after BDL in terms of activation of Akt, inhibition of GSK3ß, and blockage of caspase-9 cleavage. Furthermore, hepatocyte stellate cell activation was markedly inhibited in IGF1 gene-treated rats. Apoptosis was significantly attenuated by IGF1 gene therapy. CONCLUSIONS: This study demonstrated that gene transfer of IGF1 could attenuate hepatocellular apoptosis and injury after bile duct ligation in rats.

Toll-like receptor 4 prevents AOM/DSS-induced colitis-associated colorectal cancer in Bacteroides fragilis gnotobiotic mice.

Bacteroides fragilis (BF) plays a critical role in developing and maintaining the mammalian immune system. We previously found that BF colonization could prevent inflammation and tumor formation in a germ-free (GF) colitis-associated colorectal cancer (CAC) mouse model. The role of Toll-like receptor 4 (TLR4) in CAC development has not been clearly elucidated in BF mono-colonized gnotobiotic mice. The wild-type (WT) and TLR4 knockout (T4K) germ-free mice were raised with or without BF colonization for 28 days (GF/WT, GF/T4K, BF/WT, and BF/T4K) and then CAC was induced under azoxymethane (AOM)/dextran sulfate sodium (DSS) administration. The results showed that tumor formation and tumor incidence were significantly inhibited in the BF/WT group compared to those observed in the GF/WT group. However, the tumor prevention effect was not observed in the BF/T4K group unlike in the BF/WT group. Moreover, the CAC histological severity of the BF/WT group was ameliorated, but more severe lesions were found in the GF/WT, GF/T4K, and BF/T4K groups. Immunohistochemistry showed decreased cell proliferation (PCNA, ß-catenin) and inflammatory markers (iNOS) in the BF/WT group compared to those in the BF/T4K group. Taken together, BF mono-colonization of GF mice might prevent CAC via the TLR4 signal pathway.

Congenital midline nasal mass: cases series and review of the literature.

Encephalocele, glioma and dermoid cyst are the most common midline nasal masses. Given their potential for intracranial extension, prompt treatment is necessary to prevent complications. Herein, we present two cases of midline nasal masses. A comparison was made to delineate the differences between their clinical courses, treatments and outcomes. Case 1 was a baby girl with respiratory distress beginning at birth. Nasal glioma without definite intracranial extension was present. The mass was completely excised with the aid of a video-assisted endoscope without complications. At follow-up two years after surgery, no recurrence was noted. Case 2 was a two-year-old boy with a midline nasal dermoid cyst. Extirpation of the lesion through a vertical-dorsal approach was performed. He was discharged three days after surgery with a satisfactory aesthetic result.

Determination of urine melamine by validated isotopic ultra-performance liquid chromatography/tandem mass spectrometry.

Little is known about melamine (MEL) analysis in children's urine. In this study, an isotopic ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed and systematically validated for the analysis of MEL in urine. The method is easily performed and comprises acidification, solid-phase extraction (SPE) and UPLC/MS/MS analysis. (13)C(3)N(3)((15)NH(2))(3) was used as the internal standard (IS) for calibration. Transition ions m/z 127 > 85 of MEL and m/z 133 > 89 of the IS were used for quantification and m/z 127 > 68 of MEL was used for quantitative confirmation. Recovery and precision were assessed to guarantee the applicability of the method. The limit of quantification (LOQ) was 0.01 microg/mL while the calculated method detection limit was 0.006 microg/mL. The mean recoveries ranged from 96-99%. The method was then applied to analyze urine samples from children who had potentially consumed MEL-tainted dairy products during screening in Taiwan. Ten nephrolithiasis cases and 20 age- and gender-matched controls were selected for this study. Three out of the 10 nephrolithiasis cases had elevated levels of MEL. Comparatively, twenty age- and gender-matched non-nephrolithiasis controls consuming Taiwan brand milk powder all showed MEL levels lower than the detection limit except for two children with background levels of 0.02 microg/mL. The background level in these children urine samples was established by UPLC/MS/MS analysis. Positive results of urine MEL tests might be associated with nephrolithiasis in these candidates. Measurement of urine MEL concentration can be helpful in confirming MEL-related nephrolithiasis, but its clinical application needs further clarification.

Effects of beta-carotene on antioxidant status in rats with chronic alcohol consumption.

This study examined the effects of beta-carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and beta-carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and alpha-tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with beta-carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing beta-carotene. The results indicate that beta-carotene supplementation can prevent ethanol-induced liver damage and increase GSH concentrations in erythrocytes and the liver.

Endurance training accelerates exhaustive exercise-induced mitochondrial DNA deletion and apoptosis of left ventricle myocardium in rats.

Even though exhaustive exercise-induced oxidative stress increases the risk of tissue damage, regular endurance training is widely assumed to improve cardiac function and protects against heart disease. We tested the hypothesis that an endurance training program prevents exhaustive exercise-induced increases in cardiac dysfunction and apoptosis in left ventricle (LV). Thirty-two male Sprague-Dawley rats were randomly divided into four groups: sedentary control (C), trained (T), exhaustively exercised (E), and trained plus exhaustively exercised (TE). Rats in T and TE groups ran on a motorized treadmill for 12 weeks. Rats in groups E and TE performed an exhaustive running test on a treadmill. The main effects of training were indicated by increased running time to exhaustion (80 +/- 5 and 151 +/- 13 min for groups E and TE, respectively, P = 0.0001), myocardial hypertrophy (0.38% and 0.47% for untrained and trained rats, respectively, P = 0.0002), decreased LV ejection fraction (88% and 71% for untrained and trained rats, respectively, P < 0.0001), accelerated mitochondrial DNA 4834-bp large deletion (mtDNA4834 deletion), and up-regulated protein levels of heat shock protein-70, cytochrome C, cleaved capsase-3, and cleaved PARP in LV following a bout of exhaustive exercise. Contrary to our hypothesis, these results suggest that endurance training induced significant impairment of regional systolic and diastolic LV myocardial function and ejection fraction in rats. Our findings show that endurance training accelerates exhaustive exercise-induced mtDNA4834 deletion and apoptosis in the LV.

Protective effects of L-arginine supplementation against exhaustive exercise-induced oxidative stress in young rat tissues.

Recently, we showed that L-arginine (L-Arg) supplementation could attenuate acute exercise-induced oxidative and inflammatory stress in aging rats. In this study, we investigate whether L-Arg supplementation protects cellular oxidative stress, inflammation, or the mitochondrial DNA 4834-bp large deletion (mtDNA4834 deletion) in 14-week-old young rats tissues during exhaustive exercise. Rats were randomly divided into four groups: sedentary control (SC); SC with L-Arg treatment (SC+Arg); exhaustive exercise (E); and exhaustive exercise with L-Arg treatment (E+Arg). Rats in the SC+Arg and E+Arg groups received supplemental 2% L-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill. The results showed a significant increase in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and lipid peroxide (malondialdehyde; MDA) levels of muscular, hepatic, and renal tissues in exercised rats as compared with sedentary rats. The increased XO, MPO, and MDA levels of these tissues significantly decreased in exercised rats supplemented with L-Arg. However, exhaustive exercise had no effect on mtDNA4834 deletions of muscular and hepatic tissues. The activities of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (CRE), lactate, uric acid, non-esterified fatty acid (NEFA), and D-3-hydroxybutyrate in the plasma significantly increased in the exercised rats compared with the sedentary rats, while the CK, lactate and uric acid levels in the plasma significantly decreased in L-Arg-supplemented exercised rats. These findings suggest that L-Arg supplementation reduces the oxidative damage to and inflammatory response in skeletal muscles, the liver, and kidneys caused by exhaustive exercise in young rats.

Ubiquinol Supplementation Alters Exercise Induced Fatigue by Increasing Lipid Utilization in Mice.

Ubiquinol (QH), a reduced form of coenzyme Q10, is a lipid antioxidant that is hydro-soluble and is commonly formulated in commercial supplements. Ubiquinol has been increasingly reported to exert antioxidant functions, in addition to its role in the cell energy-producing system of mitochondria and adenosine triphosphate (ATP) production. The aim of this study was to assess the potential beneficial effects of QH on anti-fatigue and ergogenic functions following physiological challenge. Forty 8-week-old male Institute of Cancer Research (ICR) mice were divided into four groups (n = 10 for each group): Group 1 (vehicle control or oil only); Group 2 (1X QH dose or 102.5 mg/kg); Group 3 (2X QH dose or 205 mg/kg); Group 4 (6X QH dose or 615 mg/kg). Anti-fatigue activity and exercise performance were studied using the forelimb grip strength experiment and exhaustive weight-loaded swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen), creatine kinase (CK), and free fatty acids (FFA) after an acute exercise challenge. The forelimb grip strength and exhaustive weight-loaded swimming time of the QH-6X group were significantly higher than those of the other groups. QH supplementation dose-dependently reduced serum lactate, ammonia, and CK levels and increased the FFA concentration after acute exercise. In addition, QH increased the liver and muscle glycogen content, an important energy source during exercise. Therefore, the results suggest that QH formulation is a safe dietary supplement for amelioration of fatigue and for promoting exercise performance.

2-Naphthol Levels and Allergic Disorders in Children.

BACKGROUND: The measurement of polycyclic aromatic hydrocarbons (PAH) in ambient air is quite difficult to perform. Using urine biomarkers of PAH such as 2-naphthol is one approach to this problem. This study explored the association between urine 2-naphthol levels and allergic diseases. The associations between 2-naphthol levels and oxidative stress biomarkers for the possible disease pathogenesis were also investigated. METHOD: A total of 453 kindergarten children from the (Childhood Environment and Allergic Diseases Study) CEAS cohort with urine samples were recruited. Urine 2-naphthol levels were measured by high-performance liquid chromatography mass spectrometry (HPLC-MS/MS) and markers of oxidative stress (8OHdG) were measured by enzyme-linked immunosorbent assays (ELISA). Information on environmental risk factors and allergic diseases were also collected. The association between 2-naphthol levels, 8OHdG levels, IgE, and allergic diseases were evaluated by multivariate linear regression and logistic regression. RESULTS: Levels of 2-naphthol were positively correlated with 8OHdG levels. A one ln-unit increase in the 2-naphthol level was positively associated to 8OHdG levels (per ln-unit: ß = 100.61, p < 0.001). When dividing 2-naphthol levels into quartiles, asthma was significantly associated with 2-naphthol levels at a concentration of >1.60 ng/mL (adjusted OR: 3.14, 95% CI 1.34⁻7.35). CONCLUSION: Urine 2-naphthol levels are associated with markers of oxidative stress and the risk of allergic diseases in young children.

Transcriptomic analysis reveals a controlling mechanism for NLRP3 and IL-17A in dextran sulfate sodium (DSS)-induced colitis.

The incidence of inflammatory bowel disease (IBD) has markedly increased. Our research findings during the past showed that medicinal plant extracts and the derived phytochemical components from Wedelia chinensis (WC) can have strong anti-colitis activities. Here, we further identified the key component phytochemicals from active fractions of different WC preparations (WCHA) that are responsible for the protective effect of WCHA in colitis mice. Of the 3 major compounds (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g., RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals treatment, luteolin was found to strongly suppress the DSS-activated IL-17 pathway in colon tissue. In addition, co-treatment with wedelolactone and luteolin had a synergistic effect on the expression level of some IL-17 pathway-related genes. Interestingly, our NGS analyses also indicated that luteolin and wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using a 3-dimensional cell co-culture system, we further demonstrated that luteolin could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in inflamed colon tissue, which also indicates the pharmacological potential of luteolin and wedelolactone in treating IBD.

Interactions Between Bisphenol A Exposure and GSTP1 Polymorphisms in Childhood Asthma.

PURPOSE: Bisphenol A (BPA) exposure may increase the risk of asthma. Genetic polymorphisms of oxidative stress-related genes, glutathione S-transferases (GSTM1, GSTP1), manganese superoxide dismutase, catalase, myeloperoxidase, and microsomal epoxide hydrolase may be related to BPA exposure. The aim is to evaluate whether oxidative stress genes modulates associations of BPA exposure with asthma. METHODS: We conducted a case-control study comprised of 126 asthmatic children and 327 controls. Urine Bisphenol A glucuronide (BPAG) levels were measured by ultra-performance liquid chromatography/tandem mass spectrometry, and genetic variants were analyzed by a TaqMan assay. Information on asthma and environmental exposure was collected. Analyses of variance and logistic regressions were performed to determine the association of genotypes and urine BPAG levels with asthma. RESULTS: BPAG levels were significantly associated with asthma (adjusted odds ratio [aOR], 1.29 per log unit increase in concentration; 95% confidence interval [CI], 1.081.55). Compared to the GG genotype, children with a GSTP1 AA genotype had higher urine BPAG concentrations (geometric mean [standard error], 12.72 [4.16] vs 11.42 [2.82]; P=0.036). In children with high BPAG, the GSTP1 AA genotype was related to a higher odds of asthma than the GG genotype (aOR, 4.84; 95% CI, 1.0223.06). CONCLUSIONS: GSTP1 variants are associated with urine BPA metabolite levels. Oxidative stress genes may modulate the effect of BPA exposure on asthma.

The impact of time, legislation, and geography on the epidemiology of traumatic brain injury.

In 1991, a population-based epidemiologic traumatic brain injury (TBI) study was done in urban and rural areas of Taiwan; this was 5 years before the helmet use law was passed and 8 years before the drink driving law was passed. In order to evaluate the impact of three major determinants (time, geography, and legislation) on the epidemiology of TBI, we conducted a prospective study in 2001 and used the 1991 data to examine the differences in TBI distribution in urban and rural Taiwan a decade after these laws were passed. In 2001, 5754 TBI cases were collected from the urban area of Taipei City, and 1474 TBI cases were collected from the rural area of Hualien County. The TBI incidence rate in Taipei City in 2001 was estimated to be 218/100,000 population (285/100,000 for males and 152/100,000 for females). When compared to the 1991 data, the incidence rate in 2001 had increased by 20%. The TBI incidence rate in Hualien County in 2001 was estimated to be 417/100,000 population (516/100,000 for males and 306/100,000 for females); this was a 37% increase over the 1991 data. Our study found that the distribution of causes and age distribution had shifted significantly over the 10-year period. In 2001, the age group with the highest incidence was 20-29 years, while in 1991 it had been the over 70 years age group. While traffic-related TBI had decreased, falls and assaults had increased in 2001. We also found that legislation, such as the helmet law, affects TBI distribution by decreasing the traffic-related TBI rate, decreasing the admission severity of TBI, and reducing TBI-related mortality. Finally, geography plays a crucial role in the outcome of TBI; over the 10 year period, Taipei had an increase in moderately severe outcomes, while Hualien had an increase in more severe outcomes. Comparative studies of TBI in urban and rural areas have shown that time, legislation, and geography are crucial determinants of TBI epidemiology. Although time and legal interventions seem to have more of an impact, geography does affect TBI outcomes.

Phytochemicals Approach for Developing Cancer Immunotherapeutics.

Phytochemicals or their derived compounds are being increasingly recognized as potentially potent complementary treatments for cancer. Among them, some phytochemicals are being actively evaluated for use as adjuvants in anticancer therapies. For instance, shikonin and hypericin were found to induce immunogenic cell death of specific cancer cells, and this effect was able to further activate the recognition activity of tumor cells by the host immune system. On the other hand, some derivatives of phytochemicals, such as dihydrobenzofuran lignan (Q2-3) have been found to induce the secretion of an endogenous anticancer factor, namely IL-25, from non-malignant cells. These findings suggest that phytochemicals or their derivatives confer a spectrum of different pharmacological activities, which contrasts with the current cytotoxic anticancer drugs commonly used in clinics. In this review, we have collected together pertinent information from recent studies about the biochemical and cellular mechanisms through which specific phytochemicals regulate target immune systems in defined tumor microenvironments. We have further highlighted the potential application of these immunotherapeutic modifiers in cell-based cancer vaccine systems. This knowledge provides useful technological support and know how for future applications of phytochemicals in cancer immunotherapy.

Multicenter evaluation of propofol for head-injured patients in Taiwan.

BACKGROUND: The present study was a multicenter, retrospective study which aimed to evaluate the efficacy of propofol, a new choice of pharmacotherapy in head-injured patients. METHODS: Head-injured patients admitted to 3 hospitals during the period from January 2003 to December 2004 were included in this clinical trial. Data on patients' demographics, laboratory data, GCS score, ICP, CPP, concurrent medications, and therapeutic outcomes were collected. RESULTS: Among the 104 patients included, only 44 were given propofol. The average age was 40.8 +/- 22 years for all patients, with 41.91 +/- 20.41 and 43.48 +/- 23.19 years for the propofol group and nonpropofol group, respectively (P=.097). There was no significant difference in baseline GCS score between the 2 groups (5.86 +/- 1.84 vs 5.66 +/- 1.59, P=.729). Mean ICP for the first 3 days in the ICU was 17.23 +/- 9.0 mm Hg in the propofol group and 33.19 +/- 32.56 in the nonpropofol group, respectively (P=.017). Mean CPP for the first 5 days in the ICU was 71.10 +/- 15.32 mm Hg in the propofol group and 43.20 +/- 29.92 mm Hg in the nonpropofol group (P<.001). A higher survival rate was found in the propofol group (81.8% vs 46.7%, P<.001). CONCLUSIONS: The present study demonstrated that propofol improved the outcome in recovery phase of head-injured patients.