Whole Blood Concentrations Research Articles

Dependency of R2 and R2* relaxation on Gd‐DTPA concentration in arterial blood: Influence of hematocrit and magnetic field strength

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R2 (*) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time‐consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R2 (*) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open‐source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient‐echo sequence (proof‐of‐concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient‐echo and spin‐echo sequences. The results show that for both gradient‐echo and spin‐echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R2 (*) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.

Clinical Validation of a Volumetric Absorptive Micro-Sampling Device for Pharmacokinetic Studies With Tranexamic Acid.

We assessed the accuracy of tranexamic acid (TXA) concentrations measured in capillary whole blood using volumetric absorptive micro-sampling (VAMS) devices. Paired venous and VAMS capillary blood samples were collected from 15 healthy volunteers participating in a pharmacokinetic study of alternative routes (oral, IM and IV) of administering TXA. To assess accuracy across a range of concentrations, blood was drawn at different times after TXA administration. We measured TXA concentrations in plasma, whole blood from samples collected by venepuncture and whole blood from venous and capillary samples collected using VAMS devices. TXA was measured using a validated high sensitivity liquid chromatography - mass spectrometry method. We used Bland-Altman plots to describe the agreement between the TXA concentrations obtained with the different methods. In the 42 matched samples, the mean plasma TXA concentration was 14.0 mg/L (range 2.6–36.5 mg/L) whereas the corresponding whole blood TXA concentration was 7.7 mg/L (range 1.6–17.5 mg/L). When comparing TXA concentrations in VAMS samples of venous and capillary whole blood, the average bias was 0.07 mg/L (lower and upper 95% limits of agreement: −2.1 and 2.2 mg/L respectively). When comparing TXA concentrations in venous whole blood and VAMS capillary whole blood, the average bias was 0.7 mg/L (limits of agreement: −2.7 and 4.0 mg/L). Volumetric absorptive micro-sampling devices are sufficiently accurate for use in pharmacokinetic studies of tranexamic acid treatment in the range of plasma concentrations relevant for the assessment of fibrinolysis inhibition.

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients.

Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations.

Blood concentrations of new synthetic opioids.

Over the last decade, there has been a significant growth in the market and number of new psychoactive substances (NPS). One of the NPS groups that has grown rapidly in recent years, bringing a new set of problems, consists of new synthetic opioids. The extreme potency of these compounds poses a high risk of acute poisoning, as an overdose can cause respiratory depression. Most of the information regarding human pharmacokinetics of new opioids is based on toxicological case reports and the data on concentrations of new opioids in human blood are scarce. The interpretation of results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful. The data were collected by searching the PubMed and Scopus databases and by using the Google search engine. All the available data from articles and reports that measured new opioid concentrations in plasma, serum, or whole blood were included in the data analysis. The presented tables list the observed concentrations in fatal and nonfatal cases involving 37 novel synthetic opioids. Blood levels of new opioids are extremely difficult to interpret. Low blood concentrations of these substances do not rule out acute poisoning as their high potency creates a risk of respiratory depression even at low doses. Opioid tolerance, frequent presence of other drugs, and additional diseases make it impossible to define concentration ranges, especially the minimum fatal concentrations. This report provides quick access to the source articles quantifying novel synthetic opioids.

Ion-Induced Phase Transfer of Cationic Dyes for Fluorescence-Based Electrolyte Sensing in Droplet Microfluidics.

Fluorescence-based sensing in droplet microfluidics requires small sample volumes, allows for high-throughput assays, and does not suffer from photobleaching as each flowing sensor is only scanned one time. In this paper, we report a selective and sensitive fluorescence-based ion-sensing methodology in droplet microfluidics using a T-junction PDMS chip. The oil stream is doped with sensor ingredients including an ionophore, a cation exchanger, and a permanently cationic fluorophore as the optical reporter. Electrolyte cations from the aqueous sample are extracted into oil segments and displace the cationic dyes into aqueous droplets. Laser-induced fluorescence of the two immiscible phases is collected alternately, which is in clear contrast to most other ion-selective optode configurations such as nanoparticle suspensions that rely on mixed optical signals of two phases. The cation exchanger, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, is found to dramatically enhance the dye emission in the nonpolar sensing oil by preventing ion-pairing interactions and aggregations of the dye molecules, providing new insights into the mechanism of cationic dye-based ion sensors. The high dye brightness allows us to use low concentrations of sensing chemicals (e.g., 10 μM) in the oil and attain high sensitivity for detection of ions in an equal volume of sample. Using valinomycin as the ionophore and methylene blue as the dye, K+ is detected with a response time of ∼11 s, a logarithmic linear range of 10-5 to 10-2 M, a 20-fold total fluorescence response, >1000-fold selectivity against other electrolyte cations, and negligible cross-sensitivity toward the sample pH. The K+ concentration in untreated and undiluted whole blood and sweat samples is successfully determined by this microfluidic sensing method without optical interference from the droplet sample to the sensing oil. Detection of other ionic analytes can be achieved using the corresponding ionophores.

Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients-The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy.

Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with tert-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C0) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac13C,D2 as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg.

Suggested Reference Ranges of Blood Mg and Ca Level in Childbearing Women of China: Analysis of China Adult Chronic Disease and Nutrition Surveillance (2015)

Background: Magnesium and calcium play a variety of biological roles in body functions. Reference values of these elements have not yet been systematically determined in China, especially in childbearing women. We proposed to establish the reference range of Mg, Ca, and Ca/Mg ratio in plasma and whole blood for 18–44 years healthy childbearing women in China. Method: A total of 1921 women of childbearing age (18–44 years) were randomly selected from the 2015 China National Nutrition and Health Survey by taking into account the regional types and monitoring points. Among them, 182 healthy women were screened out with a series strict inclusion criteria to study the reference ranges of elements. Fundamental indicators (weight, height, waist, blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein, fast glucose, HbA1c, blood pressure, uric acid) and elements concentrations in plasma and whole blood were collected. The 2.5th to 97.5th was used to represent the reference range of Mg, Ca, and Ca/Mg ratio. Results: The reference range of Mg, Ca, and Ca/Mg ratio in plasma were 0.75–1.13 mmol/L, 2.27–3.43 mmol/L, and 2.41–3.44, respectively. Additionally, the reference range of Mg, Ca, and Ca/Mg ratio in whole blood were 1.28–1.83 mmol/L, 1.39–2.26 mmol/L, and 0.90–1.66, respectively. According to the established reference range, the prevalence of magnesium deficiency was 4.79% in 1921 childbearing women, 21.05% in type 2 diabetes, and 5.63% in prediabetes. Conclusion: The reference values of Mg, Ca and Ca/Mg proportion in plasma and entire blood of healthy childbearing women can be utilized as a pointer to assess the status of component lack and over-burden. The lower limit of plasma Mg is in good agreement with the recommended criteria for the determination of hypomagnesemia.

Biodistribution of Adeno-Associated Virus Serotype 5 Viral Vectors Following Intrathecal Injection.

The pharmacokinetic profile of AAV particles following intrathecal delivery has not yet been clearly defined. The present study evaluated the distribution profile of adeno-associated virus serotype 5 (AAV5) viral vectors following lumbar intrathecal injection in mice. After a single bolus intrathecal injection, viral DNA concentrations in mouse whole blood, spinal cord, and peripheral tissues were determined using quantitative polymerase chain reaction (qPCR). The kinetics of AAV5 vector in whole blood and the concentration over time in spinal and peripheral tissues were analyzed. Distribution of the AAV5 vector to all levels of the spinal cord, dorsal root ganglia, and into systemic circulation occurred rapidly within 30 min following injection. Vector concentration in whole blood reached a maximum 6 h postinjection with a half-life of approximately 12 h. Area under the curve data revealed the highest concentration of vector distributed to dorsal root ganglia tissue. Immunohistochemical analysis revealed AAV5 particle colocalization with the pia mater at the spinal cord and macrophages in the dorsal root ganglia (DRG) 30 min after injection. These results demonstrate the widespread distribution of AAV5 particles through cerebrospinal fluid and preferential targeting of DRG tissue with possible clearance mechanisms via DRG macrophages.

Biodistribution of 18F-FES in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant (G1T48), a Novel Selective ER Degrader.

16α-18F-fluoro-17β-estradiol (18F-FES) is a PET tracer characterizing the expression of the estrogen receptor (ER). Because therapy can interfere with the kinetics and biodistribution of 18F-FES, the aim of this study was to describe the biodistribution of 18F-FES in patients with metastatic ER-positive (ER+) breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader. Methods: Eight patients underwent 18F-FES PET/CT imaging at baseline, 4-6 wk during treatment with rintodestrant (interim), and after treatment. After intravenous administration of 200 MBq (±10%) of 18F-FES, a 50-min dynamic PET/CT scan of the thorax was obtained, followed by a whole-body PET/CT scan 60 min after injection. Blood samples were drawn for measuring whole blood and plasma activity concentration and the parent fraction of 18F-FES. Volumes of interest were placed in the aorta ascendens and in healthy tissues on both dynamic and whole-body PET scans. SUVs and target-to-blood ratios (TBRs) were calculated. Areas under the curve (AUCs) of input functions and time-activity curves were calculated as a measure of uptake in different regions. Results:18F-FES concentration in whole blood (and plasma) significantly (P < 0.05) increased at interim with median AUCs of 96.6, 116.6, and 110.3 at baseline, interim, and after treatment, respectively. In ER-expressing tissues, that is, the uterus and the pituitary gland, both SUV and TBR showed high 18F-FES uptake at baseline, followed by a decrease in uptake at interim (uterus: SUV -50.6% and TBR -58.5%; pituitary gland: SUV -39.0% and TBR -48.3%), which tended to return to baseline values after treatment (uterus: SUV -21.5% and TBR -37.9%; pituitary gland: SUV -14.2% and TBR -26.0%, compared with baseline). In other healthy tissues, tracer uptake remained stable over the 3 time points. Conclusion: The biodistribution of 18F-FES is altered in blood and in ER-expressing healthy tissues during therapy with rintodestrant. This indicates that rintodestrant alters the kinetics of the tracer, possibly affecting interpretation and quantification of 18F-FES uptake. Of note, 6 d or more after treatment with rintodestrant ended, the biodistribution returned to baseline values, consistent with recovery of ER availability after washout of the drug.

Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.

Acetylsalicylic acid is a globally used non-steroidal anti-inflammatory drug (NSAID) with diverse pharmacological properties, although its mechanism of immune regulation during inflammation (especially at in vivo relevant doses) remains largely speculative. Given the increase in clinical perspective of Acetylsalicylic acid in various diseases and cancer prevention, this study aimed to investigate the immunomodulatory role of physiological Acetylsalicylic acid concentrations (0.005, 0.02 and 0.2 mg/ml) in a human whole blood of infection-induced inflammation. We describe a simple, highly reliable whole blood assay using an array of toll-like receptor (TLR) ligands 1-9 in order to systematically explore the immunomodulatory activity of Acetylsalicylic acid plasma concentrations in physiologically relevant conditions. Release of inflammatory cytokines and production of prostaglandin E2 (PGE2) were determined directly in plasma supernatant. Experiments demonstrate for the first time that plasma concentrations of Acetylsalicylic acid significantly increased TLR ligand-triggered IL-1β, IL-10, and IL-6 production in a dose-dependent manner. In contrast, indomethacin did not exhibit this capacity, whereas cyclooxygenase (COX)-2 selective NSAID, celecoxib, induced a similar pattern like Acetylsalicylic acid, suggesting a possible relevance of COX-2. Accordingly, we found that exogenous addition of COX downstream product, PGE2, attenuates the TLR ligand-mediated cytokine secretion by augmenting production of anti-inflammatory cytokines and inhibiting release of pro-inflammatory cytokines. Low PGE2 levels were at least involved in the enhanced IL-1β production by Acetylsalicylic acid.

Effect of nickel on red blood cell parameters and on serum vitamin B12, folate and homocysteine concentrations during pregnancy with and without anemia

BackgroundResearch to date suggests that nickel affects not only the metabolism of vitamin B12 but also folates and thus may affect hematopoiesis processes. ObjectiveThe aim of the study was to examine the relationship of nickel (Ni) status to red blood cell (RBC) parameters and serum vitamin B12, folate and homocysteine concentrations in the course of normal pregnancy and in pregnant women with anemia. MethodsThe study included fifty-three pregnant women recruited to the study from the Lower Silesia region of Poland, 17 % of whom developed anemia. Nickel concentration was determined in urine, whole blood and food samples by atomic absorption spectrometry. At the same time as the food and urine samples were taken, blood was also collected for the determination of RBC parameters and serum vitamin B12, homocysteine and folate concentrations. ResultsThe median reported Ni intake, and the urinary and whole blood nickel contents for the studied pregnant women for the first trimester were respectively – 162.46 μg/day, 3.98 μg/L and 3.32 μg/L; for the second trimester – 110.48 μg/day, 6.86 μg/L and 1.04 μg/L; and for the third trimester – 132.20 μg/day, 3.41 μg/L and 0.70 μg/L. With regard to Ni concentration in whole blood (p = 0.0204) and in urine (p = 0.0003), the differences in the values for individual trimesters were statistically significant. The whole blood Ni level was significantly higher (9.28 vs 3.62 μg/L, p = 0.0114), while the concentration of homosysteine was significantly lower (4.09 vs 5.04 μmol/L, p = 0.0165) in pregnant women with anemia compared to those without anemia. The whole blood Ni concentration was negatively correlated with almost all RBC parameters in non-anemic pregnant women. ConclusionsNi status changes with the development of normal pregnancy, and in the case of anemia, an increase in Ni concentration in whole blood is observed. The demonstrated correlations between the Ni status in pregnant women and RBC parameters as well as serum vitamin B12 and folate concentrations suggest that nickel is associated with the methionine–folate cycle, iron homeostasis and bacterial synthesis of vitamin B12 in humans.

Multi-elemental determination of metals, metalloids and rare earth element concentrations in whole blood from the Canadian Health Measures Survey, 2009-2011

BackgroundAs part of Government of Canada’s Chemical Management Plan, substances containing aluminum (Al), bismuth (Bi), cerium (Ce), chromium (Cr), germanium (Ge), lanthanum (La), lithium (Li), neodymium (Nd), praseodymium (Pr), tellurium (Te), titanium (Ti) and yttrium (Y) were identified as priorities for risk assessment. Generating exposure estimates from all routes of exposure from multiple sources using a traditional approach for these elements can be challenging. The use of human biomonitoring (HBM) data would allow for direct and more precise assessment of the internal concentrations from all routes and all sources of exposure. There are no Canadian or North American population-level whole blood HBM data for the elements listed above. Therefore, this is the first biomonitoring project carried out to determine the concentrations of these elements from a nationally representative sample of Canadians. ObjectivesThe objective of this study was to generate whole blood concentrations for Al, Bi, Ce, Cr, Ge, La, Li. Nd, Pr, Te, Ti and Y in the Canadian population using biobank samples from the Canadian Health Measures Survey (CHMS) cycle 2 (2009–2011) for use in characterizing exposure in screening assessments and for establishing baseline concentrations to determine how exposures are changing over time. MethodsThe sample analysis was conducted by ICP-MS. A rigorous quality control and quality assurance process was implemented in order to generate data with high accuracy and precision while measuring low concentrations and minimizing possible inadvertent contamination. ResultsOf the elements analysed, the whole blood concentrations (μg/L) of Al, Ce, Cr, Ge, La, Nd, Pr, Te, Ti and Y in the Canadian population aged 3–79 years were below their respective method reporting limit (MRL). Two elements, Bi and Li were detected in 5 % and 66 % of the Canadian population. The median Li concentration was 0.47 μg/L. ConclusionThe results of this study provide information on concentrations of these elements in the Canadian population which can be utilized to characterize exposure in screening assessments and there by the potential for harm to human health. In addition, this study provides baseline HBM data which can be used as a comparative HBM dataset for other populations with similar exposure patterns.

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

The immature platelet fraction affects the efficacy of platelet rich plasma therapy for knee osteoarthritis.

IntroductionPlatelet-rich plasma (PRP) therapy is used to treat pathological conditions such as degenerative inflammatory diseases including osteoarthritis (OA) by enhancing tissue repair and promoting anti-inflammatory effects. Although PRP therapy for patients with knee OA improved pain and functional scores, the association of clinical outcomes and quality of PRP including cell composition and concentration is unclear.MethodsTherefore, this study analyzed blood cell counts, including the immature platelet fraction (IPF), in peripheral blood and PRP of 144 patients with knee OA who underwent PRP therapy. The mean leukocyte and platelet concentrations in whole blood and PRP were analyzed using an XN-1000 automated hematology analyzer. Visual analogue scale (VAS) scores and knee injury and osteoarthritis outcome scores (KOOS) before and 1 month after a single PRP injection were also determined.ResultsHigher platelet and lower leukocyte concentration rates were observed in PRP compared with whole blood. The platelet concentration in whole blood was negatively correlated with VAS improvement. The percentage of IPF (IPF%) in whole blood was positively correlated with VAS improvement and KOOS (pain) improvement, whereas the IPF% in PRP tended to correlate with VAS improvement. Furthermore, multivariate logistic regression demonstrated the high IPF% in whole blood was significantly associated with VAS improvement. The low percentage of neutrophil (neutrophil%) in PRP was significantly associated with the VAS improvement and KOOS (ADL) improvement.ConclusionsTherefore, PRP efficacy for OA might depend on the patient's biological status.

Validating the Use of a Quick-Read Glucometer to Assess the Glycemic Response to Short-Term Capture Stress in Two Species of Snake, Nerodia sipedon and Sistrurus miliarius

The vertebrate stress response involves the release of adrenal hormones which make stored energy available to respond to stressors. The ability to effectively mobilize and distribute glucose is an important component of successful stress coping mechanisms. While many studies of reptiles have examined the hormonal response to stress under diverse contexts, comparatively few studies have focused on the glycemic response. Here we analyze the glycemic response to short-term capture stress in two species of snake, the Northern Water Snake (Nerodia sipedon) and the Pygmy Rattlesnake (Sistrurus miliarius), across reproductive contexts using a FreeStyle Lite (FSL) glucometer. The FSL is a point-of-care glucometer that provides a fast, inexpensive, and efficient method to monitor glucose concentrations in human whole blood. However, despite increasing use in reptiles, no studies have thoroughly validated their use in snakes or other squamates. We used a traditional colorimetric glucose assay to validate results using the FSL on both fresh whole blood and stored plasma. Hyperglycemia was induced by short-term capture stress in both species. The hyperglycemic response did not vary by sex, reproductive condition, or energetic status (body condition index, BCI). However, baseline and stress-induced glucose was higher in male compared to non-reproductive female N. sipedon. In S. miliarius, the magnitude of the glycemic response was positively correlated with cloacal body temperature. Baseline glucose was below the limit of detection in many individuals of both species, which may limit the utility of the FSL and other handheld glucometers in studies that seek to describe baseline values. Glucose estimates were strongly correlated when comparing all methods, indicating that the FreeStyle Lite is a potentially valuable tool to effectively compare the glycemic response to experimental treatment or to track changes in the glycemic response of snakes over time. However, significant bias was observed when comparing the three methodologies, suggesting that caution should be used when comparing results from the FSL and other point-of-care glucometers to reference intervals generated using other methodologies.

Blood concentrations of new psychoactive substances belonging to benzodiazepine class

There has been a global increase in the number and availability of new psychoactive substances (NPS) belonging to the benzodiazepine class. New benzodiazepines are much more dangerous to health and life than pharmaceutical benzodiazepines. These substances have been associated with many deaths. Interpreting own results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful. The data collection was based on a search of PubMed, Scopus, and Google search engine. All available data from articles and reports that measured new benzodiazepine concentrations in plasma, serum, or whole blood were included in the data analysis. The presented tables list the observed concentrations in fatal and nonfatal cases involving 13 NPS belonging to the benzodiazepine class. The interpretation of the concentrations of the NPS belonging to the benzodiazepine class is difficult. Concomitant use of benzodiazepines and other drugs as well as other factors often contribute to toxic effects or deaths in real cases. This report enables quick access to the source articles quantifying new benzodiazepines.

Evaluation of the glutathione concentration in whole blood of dairy Holstein cows

The objective of this study was to evaluate the concentrations of the total (T-GSH), oxidised (GSSG) and reduced (GSH) glutathione in the blood of dairy cows, assess the relationships of the phase and number of lactation, milk production, body condition score (BCS) and selected biochemical parameters on its concentrations. We analysed 79 samples of whole blood from dairy Holstein cows. The concentration of glutathione was assessed by the spectrophotometric enzymatic method. The whole dataset shows the mean concentration of T-GSH, GSSG and GSH of 803 ± 22 µmol/l, 23 ± 2.5 µmol/l and 757 ± 27 µmol/l, respectively. The GSH/GSSG ratio was 95 ± 17. The phase of the lactation had a significant impact on the levels of T-GSH and GSH, but the number of lactation and BCS had no effect. Dry cows had higher levels of T-GSH (938 ± 44 µmol/l) than the fresh (713 ± 46 µmol/l) and peak lactation (785 ± 45 µmol/l) cows. The fresh cows had significantly lower concentrations of GSH (618 ± 44 µmol/l) than the peak lactation (719 ± 46 µmol/l) and dry cows (827 ± 43 µmol/l). On the basis of a regression analysis, blood glutathione was affected mainly by the liver function and energy metabolism. Glutathione as the marker of oxidation stress seems to be a promising tool in monitoring the health and welfare of the herd, yet intensive research in this field remains necessary.

Using blood calprotectin as a measure of blood neutrophils

Presently, bed-side or at home quantification of neutrophils in blood (b-neutrophils) is not practical, because cytometric methods are too expensive and technically demanding. We have explored whether calprotectin concentration in whole blood (b-calprotectin) might be a valid measure of b-neutrophils because this principle might be used in a simple and robust immunoassay device. We obtained heparin blood samples from 77 patients with possible neutropenia, most of them cancer patients treated with cytostatic drugs, and compared b-calprotectin with their b-neutrophils in a simultaneously taken EDTA-blood sample. The Spearman rank correlation coefficient between b-calprotectin and b-neutrophils was 0.986 (p < .0001). In a regression model of b-neutrophils as a function of age, gender, type of hematology instrument, total leukocyte count minus neutrophils, b-calprotectin, and plasma calprotectin (p-calprotectin), only b-calprotectin was a statistically significant predictor. B-neutrophils below 1 × 109/L was unlikely if b-calprotectin was above 50 mg/L. In conclusion, b-calprotectin, without adjusting for p-calprotectin, correlates closely with b-neutrophils and could be used to detect b-neutrophils below 1 × 109/L.

Essential and non-essential elements in biological samples of inhabitants residing in Nenets Autonomous Okrug of the Russian Arctic

Exposure of Arctic residents to environmental pollutants is an emerging public health problem receiving little global attention. The objective of this study was to assess whole blood concentrations of nine selected essential (Co, Cu, Mn, Se, Zn) and non-essential (As, Cd, Hg, Pb) elements among Nenets and non-Nenets adult residents of the Nenets Autonomous Okrug (NAO) living in seven coastal and inland settlements. Urine was collected in two settlements for assessment of iodine status. Altogether 297 whole blood and 68 urine samples were analysed by inductively coupled mass spectrometry and the accuracy of the measurements was assessed by use of human whole blood and urine quality control materials. Several essential and non-essential showed significant variations in whole blood concentrations characterized by gender, population group and locality. Cd levels among non-Nenets non-smokers (0.19 µg/L) indicated a dietary intake at a natural global background level. Hg concentrations in whole blood show that not more than 10% of women in the fertile age had a Hg intake above the EFAS’s recommendation. The Pb concentrations were in the range of, or partly exceeding reference values for increased risk of nephrotoxicity, and there is a need for a continued effort to reduce Pb exposure among the population groups in NAO. With high prevalence of obesity among the Nenets and non-Nenets population, a high prevalence of Fe-deficiency among menstruating women (<50 years) (37.2%) and a lower I status than recommended by WHO, these nutritional dependent components deserve further attention.

BLOOD MINERAL COMPOSITION IN RESIDENTS OF THE ARCTIC REGION WITH LOW WATER MINERALIZATION RATES IN CENTRALIZED TAP WATER SUPPLY SYSTEMS

Introduction: Mineral content of tap water vary significantly between settings and may affect blood mineral composition in humans. The evidence from Arctic Russian settings is scarce. Aim: To assess blood mineral composition among residents of areas with low mineralization of water from underground sources distributed by centralized water supply systems in Arctic Russia. Methods: The study was performed in the town of Kirovsk, Murmansk region. Only permanent residents of the town aged 18-23 years participated. Concentrations of Ag, Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Si, Sn, Sr, Ti, Tl, V, Zn, Y in tap water and whole blood were determined by atomic emission spectrometry. Results: Tap water in Kirovsk has an increased pH value, with a total mineralization of 65.0 mg/l with the legal limit of 1000 mg/l). Magnesium and calcium concentrations were 1 000-1 500 and 150-300 times below maximum permissible (MPC) concentrations, re spectively. The concentration of aluminum exceeded MPC by 30-50 % while concentrations of other elements were tens to hundreds times below MPC. In blood, calcium concentration was slightly below the average value for healthy individuals while and the magnesium content corresponded to normal values. An increased concentration of boron (2.45 ± 0.11 mg/l) was revealed. Conclusions: Contrary to expectations, residents of the area with low mineral content of tap water did not have a significant decrease in concentrations of calcium and magnesium in whole blood. No signs of increased concentration of heavy metals in blood of the residents were observed. Despite the high concentration of aluminum in water, its concentration in whole blood is within the physiological limits. At the same time, an increased blood concentration of boron was revealed warranting further research.