Strength of the Association of Elevated Vitamin B12 and Solid Cancers: An Adjusted Case-Control Study.

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 ≥ 1000 ng/L with 785 controls matched for sex and age with B12 < 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 ≥ 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.

Risks linked to accidental inoculation of humans with veterinary vaccines: a 7-year prospective study.

AIM: Accidental inoculation of humans with veterinary vaccines can lead to early and late complications. The aim of our study is to describe these complications and their risk factors. METHODS: Prospective observational study conducted from 2007 to 2014 at Angers University Hospital's Poison Control Centre. The endpoints examined were: early and late locoregional complications, surgical treatment, and absence from work. The statistical analysis was based on a multivariate analysis. DISCUSSION: The presence of mineral oil adjuvants, the injection of the vaccine under pressure and injection in joint and tendon of the hand significantly increased early locoregional complications and surgery but only the presence of mineral oil adjuvant increased significantly late locoregional complications at one month. Absence from work is significantly correlated to the site of injection and the presence of mineral oil adjuvant. CONCLUSION: It is important to know about the contents of the veterinary vaccine in order to anticipate early and late complications that may arise (particularly due to the presence of mineral oil adjuvants). Special attention must also be given do the site of injection. We think that any accidental injection of veterinary vaccine into humans, especially those containing mineral oils, must lead to an early medical consultation. This must also be indicated on the product.

Markers of oil exposure in cold-water benthic environments: Insights and challenges from a study with echinoderms.

In spite of increasing naval activities and petroleum exploration in cold environments, there is currently a paucity of tools available to monitor oil contamination in boreal marine life, especially in sedentary (non-fish) species that dominate benthic communities. This research aimed to identify biotic sources of variation in biomarkers using subarctic echinoderms, and to identify suitable biomarkers of their exposure to hydrocarbons. The focal species included the sea star Asterias rubens, the brittle star Ophiopholis aculeata, the sea urchin Strongylocentrotus droebachiensis, and the sea cucumber Cucumaria frondosa, which are among the most abundant echinoderms in the North Atlantic and Arctic Oceans. The latter two species are also commercially exploited. A series of 96-h acute exposures of the water-accommodating fraction (WAF) of used lubricating oil (ULO) were performed in different seasons (i.e. distinct reproductive stages). Digestive and reproductive tissues were analyzed for baseline and response levels of glutathione peroxidase (GPx) and ethoxyresorufin-O-deethylase (EROD). GPx activity was detected in the pyloric caecum, stomach, and gonad of sea stars, the intestine and gonad of sea cucumbers, and the gonad of brittle stars and sea urchins. No seasonal variation in baseline GPx activity occurred. Upon exposure to the ULO WAF, sex-based differences were elicited in the GPx activity of sea star stomachs (lower in females than males). EROD activity was present in the pyloric caeca of sea stars, and the gonads of brittle stars and sea urchins. An interaction between season and sex on baseline EROD activity was measured in the gonads of sea urchins. Ovaries exhibited significant seasonal variation in EROD activity and had greater activity than testes during the spawning and post-spawning seasons. Seasonal variation in EROD activity also occurred in sea star pyloric caeca and brittle star gonads. Furthermore, testes of sea urchins exposed to the ULO WAF exhibited suppressed EROD activity compared to baseline levels. The nearly universal presence of GPx activity highlights its potential as a useful biomarker, while EROD activity was much more limited. Findings suggest a complex relationship between temporal and biotic factors on both the baseline and response levels of enzymatic activity, emphasizing the need to consider sex and sampling season in studies of biomarkers of hydrocarbon exposure in boreal indicator species that display annual reproductive cycles.

Vasodilator response to galvanic current stimulation of the skin accurately detects acetylsalicylic acid intake: A study in 400 vascular patients.

BACKGROUND AND AIMS: The first cause of low-dose acetylsalicylic-acid (ASA) inefficacy is poor adherence to treatment. No non-invasive technique is available to assess ASA intake. Current-induced vasodilation (CIV) was found abolished in healthy volunteers after low-dose ASA intake. We tested clinical characteristics, treatments, and comorbid conditions influencing CIV amplitude in vascular patients. METHODS: CIV was tested in 400 patients (277 males and 123 females, aged 65.4 ±â€¯13.4 years). We focused on clinical characteristics, treatments, and comorbid conditions as covariates of CIV amplitude. We studied the CIV amplitude to covariate relationships with multivariate linear regression and receiver operating characteristics (ROC). RESULTS: The multivariate linear model determined that ASA intake within the last 48 h and the interaction between ASA intake and body mass index (BMI) were the sole covariates associated with CIV amplitude. For the whole population, the area under the ROC curve (AUC) for CIV to predict ASA intake was 0.853 [95% confidence interval (CI): 0.814-0.892]. Considering separately the areas observed for non-obese (BMI ≤30, n = 303) and obese (BMI>30, n = 93) patients, the AUC [95% CI] was 0.873 [0.832-0.915] and 0.776 [0.675-0.878], respectively (p = 0.083). CONCLUSIONS: ASA is the only drug that affects the amplitude of CIV response observed after galvanic current application to the skin of vascular patients. CIV depends on BMI but not age or gender. As such, CIV appears to be a potential objective marker of ASA intake and could facilitate future non-invasive assessments of adherence to ASA treatment.

Effects of dissolved oxygen tension and agitation rate on the production of heat-shock protein glycoprotein 96 by MethA tumor cell suspension culture in stirred-tank bioreactors.

Heat-shock protein glycoprotein (gp96) serves as a natural adjuvant for chaperoning antigenic peptide into the immune surveillance pathway. In our laboratory, MethA tumor cell suspension culture process has been recently developed for gp96 production in spinner flask. In this work, effects of dissolved oxygen tension (DOT) and agitation rate on this process were studied in stirred-tank bioreactor. The optimal conditions for gp96 production were different with those for MethA tumor cell growth. MethA tumor cell growth pattern was not much changed by various levels of DOT and agitation rate, while gp96 biosynthesis was more sensitive to DOT and agitation rate. Compared with 50% of DOT, the production and specific productivity of gp96 was increased by 27 and 66% at 10% of DOT, respectively. Compared with the agitation rate of 100 rpm, the production and volumetric productivity of gp96 was increased by 48 and 144% at the agitation rate of 200 rpm, respectively. Low DOT (i.e., 10% of air saturation) and high agitation rate (i.e., 200 rpm) were identified to be favorable for gp96 biosynthesis. The results of this work might be useful to scale-up the bioprocess into the pilot scale.

Suspension culture process of MethA tumor cell for the production of heat-shock protein glycoprotein 96: process optimization in spinner flasks.

Heat-shock proteins (HSPs) act like "chaperones", making sure that the cell's proteins are in the right shape and in the right place at the right time. Heat-shock protein glycoprotein 96 (gp96) is a member of the HSP90 protein family, which chaperones a number of molecules in protein folding and transportation. Heat-shock protein gp96 serves as a natural adjuvant for chaperoning antigenic peptides into the immune surveillance pathways. Currently, heat-shock protein gp96 was only isolated from murine and human tissues and cell lines. An animal cell suspension culture process for the production of heat-shock protein gp96 by MethA tumor cell was developed for the first time in spinner flasks. Effects of culture medium and condition were studied to enhance the MethA tumor cell density and the production and productivity of heat-shock protein gp96. Initial glucose concentration had a significant effect on the heat-shock protein gp96 accumulation, and an initial glucose level of 7.0 g/L was desirable for MethA tumor cell growth and heat-shock protein gp96 production and productivity. Cultures at an initial glutamine concentration of 3 and 6 mM were nutritionally limited by glutamine. At an initial glutamine concentration of 6 mM, the maximal viable cell density of 19.90 x 10(5) cells/mL and the maximal heat-shock protein gp96 production of 4.95 mg/L was obtained. The initial concentration of RPMI 1640 and serum greatly affected the MethA tumor cell culture process. Specifically cultures with lower initial concentration of RPMI 1640 resulted in lower viable cell density and lower heat-shock protein gp96 production. At an initial serum concentration of 8%, the maximal viable cell density of 19.18 x 10(5) cells/mL and the maximal heat-shock protein gp96 production of 5.67 mg/L was obtained. The spin rate significantly affected the cell culture process in spinner flasks, and a spin rate of 150 rpm was desirable for MethA tumor cell growth and heat-shock protein gp96 production and productivity. Not only the cell density but also the production and productivity of heat-shock protein gp96 attained in this work are the highest reported in the culture of MethA tumor cell. This work offers an effective approach for producing heat-shock protein glycoprotein 96 from the cell culture process. The fundamental information obtained in this study may be useful for the efficient production of heat-shock protein by animal cell suspension culture on a large scale.