The effect of ongoing blood loss on human serum concentrations of perfluorinated acids

Perfluorinated alkyl acids (PFAAs) have been detected in serum at low concentrations in background populations. Higher concentrations haven been observed in adult males compared to females, with a possible explanation that menstruation offers females an additional elimination route. In this study, we examined the significance of blood loss as an elimination route of PFAAs. Pooled serum samples were collected from individuals undergoing a medical procedure involving ongoing blood withdrawal called venesection. Concentrations from male venesection patients were approximately 40% lower than males in the general population for perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). A simple pharmacokinetic model was used to test the hypothesis that blood loss could explain why adult males have higher concentrations of PFAAs than females, and why males undergoing venesections had lower concentrations compared to males in the general population. The model application generally supported these hypotheses showing that venesection might reduce blood serum concentrations by 37% (PFOA) and 53% (PFOS) compared to the observed difference of 44% and 37%. Menstruation was modeled to show a 22% reduction in PFOA serum concentrations compared to a 24% difference in concentrations between males and females in the background population. Uncertainties in the modeling and the data are identified and discussed.

CXCL10, CXCL11, HLA-A and IL-1β are induced in peripheral blood mononuclear cells from women withChlamydia trachomatisrelated infertility

Chlamydia trachomatis infections can result in the development of serious sequelae such as pelvic inflammatory disease and tubal infertility. In this study, peripheral blood mononuclear cells from women who were undergoing or had recently undergone IVF treatment were cultured ex vivo with C. trachomatis to identify the immune responses associated with women who had serological evidence of a history of Chlamydia infection. Cytokines secreted into the supernatant from the cultures were measured using ELISA, and the level of IL-1β was found to be significantly higher in Chlamydia positive women than Chlamydia negative women. qRT-PCR analysis of the expression of 88 immune-related genes showed trends towards an upregulation of CXCL10, CXCL11 and HLA-A in Chlamydia positive women compared with Chlamydia negative women. These findings support that some women launch a more marked proinflammatory response upon infection with C. trachomatis and this may be associated with why C. trachomatis induces infertility in some infected women.

Building a flexible, voluntary donation panel: An exploration of donor willingness

BACKGROUND As blood collection agencies (BCAs) face recurrent shortages of varying blood products, developing a panel comprising donors who are flexible in the product they donate based on same-time inventory demand could be an efficient, cost-effective inventory management strategy. Accounting for prior whole blood (WB) and plasmapheresis donation experience, this article explores current donors’ willingness to change their donation product and identifies the type of information required for such donation flexibility. STUDY DESIGN AND METHODS Telephone interviews (mean, 34 min; SD, 11 min) were conducted with 60 donors recruited via stratified purposive sampling representing six donor groups: no plasma, new to both WB and plasma, new to plasma, plasma, flexible (i.e., alternating between WB and plasma), and maximum (i.e., high frequency alternating between WB and plasma) donors. Participants responded to hypothetical scenarios and open-ended questions relating to their and other donors’ willingness to be flexible. Responses were transcribed and content was analyzed. RESULTS The most frequently endorsed categories varied between donor groups with more prominent differences emerging between the information and support that donors desired for themselves versus that for others. Most donors were willing to change donations but sought improved donation logistics and information regarding inventory levels to encourage flexibility. The factors perceived to facilitate the flexibility of other donors included providing donor-specific information and information regarding different donation types. CONCLUSION Regardless of donation history, donors are willing to be flexible with their donations. To foster a flexible donor panel, BCAs should continue to streamline the donation process and provide information relevant to donors’ experience.

Negative experiences and donor return: An examination of the role of asking for something different

BACKGROUND Negative donation experiences, including vasovagal reactions, deter donor retention. However, whether this deterrence effect varies as a function of whole blood (WB) donation history and requests to donate the same or a different product remains unclear. STUDY DESIGN AND METHODS The responses of 894 eligible WB donors who had been approached to convert to plasmapheresis and 954 eligible first-time plasmapheresis donors who had been surveyed on their last donation experience and their intention to donate plasma were considered. This information was matched with individual vasovagal reaction records, deferral category, WB donation history, and subsequent donation behavioral data obtained from the blood collection agency. RESULTS Path analysis indicated that the application of a deferral and an officially recorded vasovagal reaction decreased donors' intentions to continue plasmapheresis donation, but had no effect on WB donors' intentions to convert to plasmapheresis. Consistent with past findings, vasovagal reactions occurred more frequently with female and inexperienced donors. CONCLUSION Experiencing vasovagal reactions and deferrals may not universally deter donors from continuing to donate. Rather, the offer to convert to another form of donation—in this instance, plasmapheresis—after experiencing a negative donation event while donating WB may be sufficient to eliminate the deterrence effect on retention.

A novel fully validated LC–MS/MS method for quantification of pyridoxal-5′-phosphate concentrations in samples of human whole blood

Quantification of pyridoxal-5´-phosphate (PLP) in biological samples is challenging due to the presence of endogenous PLP in matrices used for preparation of calibrators and quality control samples (QCs). Hence, we have developed an LC-MS/MS method for accurate and precise measurement of the concentrations of PLP in samples (20 µL) of human whole blood that addresses this issue by using a surrogate matrix and minimizing the matrix effect. We used a surrogate matrix comprising 2% bovine serum albumin (BSA) in phosphate buffer saline (PBS) for making calibrators, QCs and the concentrations were adjusted to include the endogenous PLP concentrations in the surrogate matrix according to the method of standard addition. PLP was separated from the other components of the sample matrix using protein precipitation with trichloroacetic acid 10% w/v. After centrifugation, supernatant were injected directly into the LC-MS/MS system. Calibration curves were linear and recovery was > 92%. QCs were accurate, precise, stable for four freeze-thaw cycles, and following storage at room temperature for 17h or at -80 °C for 3 months. There was no significant matrix effect using 9 different individual human blood samples. Our novel LC-MS/MS method has satisfied all of the criteria specified in the 2012 EMEA guideline on bioanalytical method validation.

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.