AG Carriers Research Articles

Gas-filled microbubble-mediated delivery of antigen and the induction of immune responses

The use of well characterized recombinant or purified protein antigens (Ag) for vaccination is of interest for safety reasons and in the case where inactivated pathogens are not available (cancer, allergy). However it requires the addition of adjuvants such as Ag carrier or immune stimulators to potentiate their immunogenicity. In this study, we demonstrated that gas-filled microbubbles (MB) can serve as an efficient Ag delivery system to promote phagocytosis of the model Ag ovalbumin (OVA) without the need of ultrasound application. Once internalized by DC, OVA was processed and presented to both CD4 and CD8 T cells in vitro; such observations were coupled with the capacity of MB to activate DC. In vivo administration of MB-associated OVA in naïve wild-type Balb/c mice resulted in the induction of OVA-specific antibody and T cell responses. Detailed characterization of the generated immune response demonstrated the production of both IgG1 and IgG2a serum antibodies, as well as the secretion of IFN-γ and IL-10 by splenocytes. Interestingly, similar results were obtained with human DC in regards of Ag delivery and cell activation. Therefore, the data presented here settle the proof of principle for the further evaluation of MB-based immunomodulation studies.

Abstract 681: Prognostic role of Perp in breast cancer

Abstract Perp, a tetraspan plasma membrane protein, is activated by p53 during apoptosis and is also regulated by p63 where it functions as an essential component of the desmosome and contributes to epithelial integrity. A single nucleotide polymorphism (SNP) in Perp was identified by its effect on apoptotic efficiency in irradiated lymphoblastoid cell lines. Therefore, this SNP may have functional significance in clinical outcomes of cancer. In this study, this SNP in PERP was evaluated as a prognostic marker and in its relationship to other known prognostic factors. Genotyping was performed on DNA isolated from peripheral blood of 1020 patients with breast cancer and genotypes were linked with annotated clinical information. Analysis of recurrence free survival was performed on a subset limited to 790 Caucasians. Among Caucasian cases, homozygous SNP genotypes were nearly equally distributed (AA: 25% and GG: 26%). Using a COX proportional hazards survival analysis, the AA genotype was found to be an independent predictor of worse recurrence-free survival (RFS, hazard ratio [HR]: 1.95, 95% CI: 1.38-2.76, p=0.0001). RFS was similar between AG and GG carriers and was more favorable as compared to AA carriers. For patients receiving breast-conserving surgery followed by radiation, patients diagnosed at or above 51 years of age or patients with stage III disease, the deleterious effect of AA genotype on RFS was more significant. In addition, the AA genotype associated with decreased RFS in subgroups of Caucasian cases regardless of stratification by hormone receptor status, HER2 status, and whether they received chemotherapy or hormonal therapy. Adjusting for effects due to stage and chemotherapy, this association remained significant in estrogen receptor positive and progesterone receptor negative cases. We also analyzed the NCI-60 cell line panel for an association between this polymorphism and response to 132 standard chemotherapeutic drugs. A significant association was observed with respect to genotype and response to anti-mitotic agents. Collectively, cell lines with the AA genotype were more sensitive to anti-mitotic agents than the GG genotype. Clinical data suggest that the AA genotype of Perp has a functional phenotype leading to increased risk of recurrence. Further studies are needed to determine the mechanism behind this association, but ultimately this SNP may be useful as a prognostic marker in breast cancer and could be used as a tool to optimize treatment strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 681. doi:1538-7445.AM2012-681

Dissolvable Trimolybdate Nanowires as Ag Carriers for High-Efficiency Antimicrobial Applications

Elimination of bacteria and other microbes effectively is important to our daily life and a variety of medical applications. Here, we introduce a new kind of trimolybdate nanowires, namelyAg2−x(NH4)xMo3O10⋅3H2O, that carry a large amount of Ag atoms in the lattice and Ag-rich nanoparticles on the surface. These nanowires can eliminate bacteria ofE. coli,Staphylococcus aureus, and unknown microbes in raw natural water with high efficiency. For example, they can inactivate more than 98% ofE. coliwith a nanowire concentration of only 5 ppm in the solution. The excellent sterilization performance is attributed to the combined effects of Ag ions, Mo ions, and Ag-rich nanoparticles of theAg2−x(NH4)xMo3O10⋅3H2Onanowires. These nanowires are not dissolvable in deionized water but can be dissolved by the metabolic materials released from bacteria, making them attractive for many biological applications.

Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed. Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage IV had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment.

Prognostic Role of Host Immune Gene Polymorphisms for Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab and Chemotherapy. A Study Based on 554 Patients Included in the GELA (Groupe d'Etude des Lymphomes de l'Adulte) Prospective Multicentric Program LNH2003,

Abstract 3676 Background:Diffuse Large B-cell Lymphoma (DLBCL) is a heterogeneous disease based on biological analyses of tumor cells, with for instance the determination of two molecular subgroups, one with a profile close to germinal center B-cells and the second to activated B-cells. Data from the biology of tumor microenvironment could also be helpful to define different prognostic subgroups of DLBCL. The role of the biology of the patient with DLBCL, i.e. the host-related factors is little explored. Epidemiological studies showed that some inherited genetic variation in immune genes could increase the risk of lymphoma development and some retrospective studies indicated that patient’s outcome could be predicted by some germ line polymorphisms (SNPs) in cytokine genes. The aim of this study is to determine the prognostic impact of 13 SNPs in 7 immune genes, IL10 (4 SNPs), Tumor Necrosis factor α (TNFA), lymphotoxin α (LTA), BAFF (3 SNPs), IL1A, IL8RB, IL4R (2 SNPs) in a cohort of newly diagnosed DLBCL patients included in the GELA LNH2003 prospective trials all treated by rituximab combined with chemotherapy.Patients and Methods: 1564 patients from France, Switzerland and Belgium were included in the 5 prospective multicentric trials of the LNH2003 program of the GELA designed for DLBCL patients who were stratified in different subgroups based on age and International Prognostic Index (IPI) score. A sample of peripheral blood lymphocytes was collected before treatment from 760 patients who signed a specific consent form for this genetic study. After pathologic review and exclusion of patients not receiving rituximab (48 patients), 554 DLBCL patients were available for this study. SNPs were genotyped using a TaqMan® based assay. Results:The median age of the 554 patients was 61 years (range, 18–93 years), 57% of them were male and 50% of patients presented at diagnosis a 2–3 age-adjusted IPI score. Chemotherapy regimen consisted in a combination of rituximab with CHOP-21 (110 patients, 20%), CHOP-14 (181 patients, 33%), low dose CHOP for patients older than 80 years (60 patients, 11%), or ACVBP regimen (203 patients, 36%). At the end of treatment, complete response (CR) or unconfirmed CR was observed in 75% of patients. After a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) was 70.2% and 75.7%, respectively. All the polymorphism distributions of the SNPs analyzed were consistent with Hardy-Weinberg equilibrium. The main initial clinical characteristics of patients were not different according to the 13 studied SNPs, except for IL4R (rs2107356), CC carriers presented less frequently B symptoms than CT and TT carriers (28% vs. 41% and 61%, P = .01). No correlation was observed between the quality of the response at the end of the treatment and each genotype of the 13 studied SNPs. The 3-year PFS and OS were overall not influenced by the genotyping of the 13 SNPs. However, a trend for a better 3-year PFS for LTA +252GG carriers compared to LTA +252AG and AA carriers was observed (79.7% vs. 64.6% and 72.7%, P = .04). Conclusions:To our knowledge, this is the largest prospective multicentric study that investigates the role of immune SNPs on treatment response and outcome in a large cohort of newly diagnosed patients with DLBCL receiving rituximab. No correlation between SNPs and treatment response was observed. Analyses of the impact on outcome of each individual SNP showed only a trend for a prognostic role on PFS of LTA A252G SNP, which is already described as a functional SNP. The results will be further precise by the correlation of IL10, BAFF and TNFA /LTA full haplotypes with response and outcome. Disclosures:No relevant conflicts of interest to declare.

Enhanced Antigen Processing of Flagellin Fusion Proteins Promotes the Antigen-Specific CD8+ T Cell Response Independently of TLR5 and MyD88

Flagellin is a highly effective adjuvant for CD4(+) T cell and humoral immune responses. However, there is conflicting data in the literature regarding the ability of flagellin to promote a CD8(+) T cell response. In this article, we report that immunization of wild-type, TLR5(-/-), and MyD88(-/-) adoptive transfer recipient mice revealed the ability of flagellin fusion proteins to promote OVA-specific CD8(+) T cell proliferation independent of TLR5 or MyD88 expression by the recipient animal. Wild-type and TLR5(-/-) APCs were able to stimulate high levels of OVA-specific CD8(+) T cell proliferation in vitro in response to a flagellin fusion protein containing full-length OVA or the SIINFEKL epitope and 10 flanking amino acids (OVAe), but not to OVA and flagellin added as separate proteins. This effect was independent of the conserved regions of flagellin and occurred in response to OVAe alone. Comparison of IFN-γ production by CD8(+) effector cells revealed higher levels of SIINFEKL peptide-MHC I complexes on the surface of APCs that had been pulsed with OVAe-flagellin fusion proteins than on cells pulsed with OVA. Inhibition of the proteasome significantly reduced Ag-specific proliferation in response to OVAe fusion proteins. In summary, our data are consistent with the conclusion that flagellin-OVA fusion proteins induce an epitope-specific CD8(+) T cell response by facilitating Ag processing and not through stimulatory signaling via TLR5 and MyD88. Our findings raise the possibility that flagellin might be an efficient Ag carrier for Ags that are poorly processed in their native state.

Liver Stiffness Measurements in Inactive Hbs AG Carriers

Liver Stiffness Measurements in Inactive Hbs AG Carriers

FcγRIIB polymorphisms, periodontitis and preterm birth in Japanese pregnant women

Recently, numerous studies have investigated the association of preterm birth with periodontitis. FcγRIIb is a human low-affinity receptor for immunoglobulin G (IgG). We have previously demonstrated single nucleotide polymorphisms (SNPs) of FcγRIIb to be associated with periodontitis and the serum-specific IgG level against periodontopathic bacteria. In this study, we investigated whether FcγRIIB gene polymorphisms were associated with periodontitis and/or pregnancy outcome. We assessed the periodontal conditions of 122 Japanese pregnant women within 5 d of delivery, and polymorphisms in FcγRIIB and in other Fcγ receptors were detected from the genomic DNA. Using clinical and genomic data, we analyzed the relationship between periodontitis, preterm birth and Fcγ receptor polymorphisms. A significant difference was observed in the distribution of FcγRIIB-nt645+25A/G (rs2125685) between preterm and term birth groups, with a higher prevalence of nt645+25AA in the preterm birth group (p = 0.032). Additionally, the FcγRIIB-nt645+25GG carrier showed significantly higher results for the prevalence of periodontitis (p = 0.048), mean pocket depth (p = 0.021), mean clinical attachment level (p = 0.010), percentage of sites with pocket depth ≥ 4 mm (p = 0.005) and percentage of sites with clinical attachment level ≥ 3 mm (p = 0.007) than the AA carrier. An association between preterm birth and periodontitis was not observed in this study. These findings suggest that FcγRIIB-nt645+25AA carriers are more likely to experience preterm birth than FcγRIIB-nt645+25AG and GG carriers. Also, women with FcγRIIB-nt645+25G exhibited a greater tendency to have periodontitis than those with nt645+25A.

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which significantly promote proliferation of cancer cells in vitro and in vivo. We looked for a possible association between human CYP2C19*3 gene polymorphism and breast cancer in the Chinese Han population. In a Chinese Han case-control study of breast cancer patients (N = 600) and age- and gender-matched healthy controls (N = 600), we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in breast cancer patients than in control subjects (6.67 vs 3.00%; P = 0.003). The odds ratio for carriers of AG + AA genotype for breast cancer was 2.31 (95% confidence interval = 1.27-4.43). Among patients, estrogen receptor, tumor size, histologic grade, presence of primary lymphonode metastases, progesterone receptor positivity, and age at diagnosis were not found to be significantly associated with CYP2C19*3 genotypes (all P > 0.05). We conclude that the CYP2C19*3 gene polymorphism is associated with breast cancer risk in Chinese Han women.

Associations of polymorphisms of methionine synthase A2756G and methionine synthase reductase G66A with the risks of coronary artery disease: a meta-analysis

To evaluate the associations between polymorphisms of methionine synthase(MTR) A2756G and methionine synthase reductase(MTRR) G66A and risk of coronary artery disease. Literatures in Medline reporting the relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of coronary artery disease from January 1990 to May 2010 were searched. A total of 14 relevant articles were selected and 13 of them met the criteria. A Meta-analysis was performed to estimate the pooled odds ratio (OR) to evaluate the relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of coronary artery disease. All analyses were performed using the STATA statistical software. Among the 13 studies, eight case-control studies containing 2143 cases of coronary artery disease and 2270 controls were included in the analysis of MTR A2756G and risk of coronary artery disease. Meanwhile, five case-control studies with 811 cases of coronary artery disease and 387 controls were included in the analysis of MTRR G66A and risk of coronary artery disease. In the analysis of MTRR G66A related to the risk of coronary artery disease, there were 246 GG carries, 397 AG carriers and 168 AA carriers in the group of coronary artery disease, against 102 GG carriers, 203 AG carriers and 82 AA carriers in the control group. Compared with the MTRR GG carriers, the risk of coronary artery disease decreased significantly by 27% (OR = 0.73, 95%CI: 0.54 - 0.99) and 25% (OR = 0.75, 95%CI: 0.56 - 1.00) (Egger's test t = -0.19, P = 0.862) in the MTRR 66 AG and AG/AA carriers, respectively, and also decreased in the MTRR AA carriers but significant difference was observed (OR = 0.84, 95%CI: 0.42 - 1.68). There was no significant association between coronary artery disease and MTR A2756G. These results suggest that MTRR66 may play a role in coronary artery disease susceptibility. MTRR 66 A allele carries are associated with a statistically significant decreased risk of coronary artery disease susceptibility.

EFFECTIVE COMMERCIAL ADDITIVES FOR IMPROVING POLY- PROPYLENE FIBRES PROPERTIES BY THE MELT EXTRUSION PROCESS

The effect of three commercial inorganic additives supplied by Ciba Speciality Chemicals, Germany namely, Irgaguard B 5000 (carrier of Ag/ Zn zeolite), Irgaguard B7000 (carrier of Ag / Zn glass) and Irgaguard 1000 (triclosan) on the properties of polypropylene fibers was studied. These additives 0.1- 2 %(w/w) concentrations were well mixed to preheated isotatic PP chips and added into the hopper tanks of a Fourne’ double extruders machine together with purged nitrogen gas and melt extruded at 250ºC to produce the continuous fibers.

Effects of TiO 2 coating dosage and operational parameters on a TiO 2/Ag photocatalysis system for decolorizing Procion red MX-5B

In this study, titanium dioxide (TiO 2) powder was coated onto the surface of a dendritic silver (Ag) carrier to synthesize TiO 2/Ag for decolorizing Procion red MX-5B (MX-5B), and related operation factors were also studied. The results showed that even without ultraviolet-A (UVA) irradiation, the Ag carrier from the TiO 2/Ag catalyst had oxidizing ability, which could effectively degrade MX-5B color, but TiO 2 was ineffective. In addition, TiO 2 from TiO 2/Ag demonstrated photocatalysis performance when irradiated, and the Ag carrier further showed an electron-scavenging ability to mitigate electron–hole pair recombination, which can improve the photocatalytic efficacy. With the oxidization and electron-scavenging ability of Ag and the photocatalysis ability of TiO 2, TiO 2/Ag can decolor MX-5B more efficiently than TiO 2. The heavier Ag carrier also improves the solid–liquid separation of nano-TiO 2, making TiO 2/Ag more suitable for application in slurry systems of photocatalytic water treatment. When the TiO 2/Ag coating ratio was 50% by weight, there was a sufficient amount of TiO 2 on Ag's surface with a good distribution, and it exhibited a good photocatalysis decolorizing effect. In a study of how operational factors impact the decolorizing of MX-5B in the TiO 2/Ag photocatalysis system with UVA irradiation (UVA-TiO 2/Ag), the decolorization efficiency was optimal when the solution was maintained at pH 6.35. The addition of 0.01 M hydrogen peroxide (H 2O 2) aided the photocatalysis decolorization efficiency, although excessive H 2O 2 reacted with hydroxyl free radicals and decreased the active groups in the system, thereby reducing the photocatalysis activity. An operating temperature of 40 °C was conducive to MX-5B decolorization, which was better than operating at room temperature.

Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study

BackgroundMutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well.MethodsIn this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156).ResultsBased on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1–2.6], AA carriers OR = 1.8 [1.2–2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1–1.9], AA carriers OR = 1.6 [1.0–2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4–2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers.ConclusionThese results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.

Efficient Synthesis of a New Podand and Application as a Suitable Carrier for Silver Ion‐Selective Electrode

AbstractA new podand of 1,1′‐thia‐bis‐[1‐(chloroethan‐2‐acetamid‐α‐oxy)] naphtol was synthesized and used as a suitable carrier for Ag+ PVC membrane electrode. The electrode exhibited linear response with a Nernstian slope of (59.5±0.8 mV/decade) within a wide concentration range of 1.0×10−7 to 1.5×10−2 mol L−1 silver ions. The electrode had a fast response time of <10 s and detection limit of 8.6×10−8 mol L−1 with a working pH range from 3.7 to 9.0. The electrode was highly selective for Ag(I) ions over a large number of cations such as alkali, alkaline earth, and heavy metal ions. The proposed sensor has been applied as an indicator electrode for indirect determination of vitamin B1 in tablets by determination of Cl− ions in this compound with a standard solution of Ag(NO3).

Aspects of the in vitro bioactivity and antimicrobial properties of Ag+- and Zn2+-exchanged 11 Å tobermorites

11 A tobermorite, Ca(5)Si(6)O(16)(OH)(2) . 4H(2)O, is a layer lattice ion exchange mineral whose potential as a carrier for Ag(+) and Zn(2+) ions in antimicrobial, bioactive formulations has not yet been explored. In view of this, the in vitro bioactivity of Ag(+)- and Zn(2+)-exchanged 11 A tobermorites and their bactericidal action against S. aureus and P. aeruginosa are reported. The in vitro bioactivity of the synthetic unsubstituted tobermorite phase was confirmed by the formation of bone-like hydroxycarbonate apatite (HCA) on its surface within 48 h of contact with simulated body fluid. The substitution of labile Ag(+) ions into the tobermorite lattice delayed the onset of HCA-formation to 72 h; whereas, the Zn(2+)-substituted phase failed to elicit an HCA-layer within 14 days. Both Ag(+)- and Zn(2+)-exchanged tobermorite phases were found to exhibit marked antimicrobial action against S. aureus and P. aeruginosa, two common pathogens in biomaterial-centred infections.

Association between estrogen receptor α gene polymorphisms and early restenosis after eversion carotid endarterectomy and carotid stenting

ObjectiveOur aim was to identify the role of PvuII and XbaI polymorphisms of the ESR1 (estrogen receptor alpha) gene in the occurrence of early restenosis after carotid endarterectomy and carotid artery stenting. MethodsIn a non-randomized prospective study we analysed blood samples from 172 patients (105 men) with severe stenosis of the internal carotid artery, using the PCR-RFLP method. Patients were treated either by carotid endarterectomy (n=82) or carotid artery stenting (n=90), and were followed-up by ultrasonography with a median follow-up time of 12 months (7.32–14.65 months). Conventional laboratory parameters were also recorded. Restenosis (>50%) rates were compared between patients carrying different genotypes and risk factors were calculated by using multivariate logistic regression. ResultsAllelic frequencies were similar between sexes (C/T allele, 0.40/0.60 and 0.43/0.57; p=0.67; G/A allele, 0.35/0.65 and 0.32/0.68; p=0.65; in men and women, respectively). Significantly higher restenosis rate was observed in patients homozygous for the A-allele of the XbaI polymorphism as compared to carriers of AG and GG genotypes (23.4% vs. 10.5%, p=0.02). TT and TC genotypes of the PvuII polymorphism were also associated with greater restenosis rate, as compared with genotype CC (19.3% vs. 3.1%, p=0.02). Associations for both polymorphisms were more expressed in women and in CEA patients. At multivariate analysis, T-A haplotype was a predictor of restenosis in the whole patient cohort (adjusted odds ratio, 7.85; 95% CI, 1.01–60.98). ConclusionPresence of A and T alleles (of the XbaI and PvuII polymorphisms, respectively) were associated with higher incidence of carotid restenosis, while the presence of G and C alleles (of the XbaI and PvuII polymorphisms, respectively) were associated with lower incidence of carotid restenosis.

Association of Sequence Variations in Vitamin K Epoxide Reductase and γ-Glutamyl Carboxylase Genes with Biochemical Measures of Vitamin K Status

Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity may be explained by differences in vitamin K status. Men and women (n=416, 60-80 y), primarily of European descent, were genotyped for common polymorphisms in VKORC1 and GGCX. Cross-sectional associations exist between polymorphisms and biochemical markers of vitamin K [plasma phylloquinone, percent undercarboxylated osteocalcin (%ucOC)]. VKORC1 rs8050894 GG homozygotes had significantly higher cross-sectional measures of plasma phylloquinone than carriers of the CG or CC genotypes (plasma phylloquinone geometric means: GG 0.874+/-0.092 versus CG/CC 0.598+/- 0.044; p=0.020), whereas carriers of VKORC1 rs7294 AA or AG had significantly lower plasma phylloquinone concentrations compared to GG homozygotes (plasma phylloquinone geometric means: 0.579+/-0.045 versus 0.762+/-0.057; p=0.035). Cross-sectional analyses also revealed that heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower %ucOC relative to either homozygous group. Polymorphisms in genes encoding enzymes involved in vitamin K metabolism may modulate plasma concentrations of phylloquionone and percent carboxylation of osteocalcin.

Ag +- and Zn 2+-exchange kinetics and antimicrobial properties of 11 Å tobermorites

Ag +- and Zn 2+-exchanged zeolites and clays have been used as coatings and in composites to confer broad-spectrum antimicrobial properties on a range of technical and biomedical materials. 11 Å tobermorite is a bioactive layer lattice ion exchanger whose potential as a carrier for Ag + and Zn 2+ ions in antimicrobial formulations has not yet been explored. In view of this, batch Ag +- and Zn 2+-exchange kinetics of two structurally distinct synthetic 11 Å tobermorites and their subsequent bactericidal action against Staphylococcus aureus and Pseudomonas aeruginosa are reported. During the exchange reactions, Ag + ions were found to replace labile interlayer cations; whereas, Zn 2+ ions also displaced structural Ca 2+ ions from the tobermorite lattice. In spite of these different mechanisms, a simple pseudo-second-order model provided a suitable description of both exchange processes ( R 2 ≥ 0.996). The Ag +- and Zn 2+-exchanged tobermorite phases exhibited marked bacteriostatic effects against both bacteria, and accordingly, their potential for use as antimicrobial materials for in situ bone tissue regeneration is discussed.

Hépatite chronique B : situations rares : dialyse, transplantation rénale et traitements pré-emptifs en situation d’immunosuppression

Parenteral and community-acquired routes of contamination sanguins of hepatitis B virus (HBV) explain its frequency (9 to 20%) in dialysis patients and kidney recipients. In dialysis, HBV infection has few impact on morbidity and mortality; by contrast, in kidney recipients HBV: 1. reduces the allograft survival; 2. the patients survival in association with a frequent and rapid evolution to cirrhosis and hepatocellular carcinoma or rare cholestatic fibrosis. Finally, cirrhosis contra-indicates renal transplantation alone given its poor short-term prognosis and a combined liver-kidney transplantation has to be discussed. Thus, it is necessary to evaluate the liver severity of the liver disease. The treatement of HBV in allograft recipients and dialysis is based on nucleos(t)idic analogues like in the general population with the same advantages and questions. The variations of the immune status either in an HBV-infected patients at the induction or at the reduction of chemotherapies (solid tumors or hemopathies) or allograft transplantation may result in two, potentially severe, events in miror: a reactivation or a spontaneous discontinuation of viral replication (seronconversion). These risks evidence that any HBs Ag carrier exposed to immune suppression has to be diagnosed, evaluated for viral replication and underlying liver disease and has to be treated by a so-called pre-emptive treatment based on analogues.

MCP-1 Promoter Polymorphism at −2518 Is Associated with Metastasis of Nasopharyngeal Carcinoma after Treatment

We herein examined whether the single nucleotide polymorphism (SNP) at -2518 of the MCP-1 gene promoter region influences clinical outcomes among nasopharyngeal carcinoma (NPC) patients. The study population consisted of 411 NPC patients without metastasis at diagnosis. All patients were treated at the Chang Gung Memorial Hospital from March 1994 to November 2004. The MCP-1 SNP-2518 genotype of each patient was determined by TaqMan genotyping kit. Statistical analyses were conducted to compare disease-specific survival (DSS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) of patients according to genotype. MCP-1 expression in tumor biopsies was examined by immunohistochemistry. Among 411 NPC patients, carriers of AA and AG genotypes were prone to distant metastasis than that of GG genotype (hazard ratio, 2.21; P = 0.017, and hazard ratio, 2.23; P = 0.005, for AA and AG genotype, respectively) after initial radiotherapy. No genotype-specific significant difference was found in DSS, PFS, and LRFS. Furthermore, immunohistochemistry revealed that MCP-1 expression level was higher in NPC tumor cells from GG carriers compared with those from AA and AG carriers. MCP-1 SNP-2518 may be a valuable genetic marker for assessing the risk of developing distant metastasis after the radiotherapy in NPC patients. Carriers of A allele may require more aggressive chemotherapy implicating a potential marker for personalized medicine. We speculate that a regulatory SNP may be associated with the distant metastasis of NPC. Validation studies are warranted.