Low Blood Concentrations Research Articles

The Blood Cytokine Profile of Young People with Early Ischemic Heart Disease Comorbid with Abdominal Obesity.

Objective: The aim was to study the blood cytokine/chemokine profile of 25–44-year-old people with early ischemic heart disease (IHD) comorbid with abdominal obesity (AO). Methods: A cross-sectional medical examination of subjects in Novosibirsk, Russia, was conducted after random sampling of the above age group. A total of 1457 subjects, 804 females and 653 males, were analyzed. The epidemiological diagnosis of IHD was made in accordance with 17 validated and functional criteria, employing exercise ECG for confirmation. Simultaneous quantitative analyses of 41 cytokines/chemokines in blood serum were performed by a multiplex assay using the HCYTMAG-60K-PX41 panel (MILLIPLEX MAP) on a Luminex 20 MAGPIX flow cytometer, with additional ELISA testing. Results: Flt3 ligand, GM-CSF, and MCP-1 were significantly associated with the relative risk of early IHD. In the presence of AO, GM-CSF, MCP-1 and IL-4 also significantly correlated with the relative risk of early IHD. By univariate regression analysis, the relative risk of early IHD was associated with lowered blood concentrations of Flt3 ligand, whereas the relative risk of early IHD in the presence of AO was associated with lowered blood concentrations of GM-CSF. Employing multivariable regression analysis, only lower blood levels of Flt3 ligand were associated with a relative risk of early IHD, whereas the relative risk of early IHD in the presence of AO was limited to lower levels of IL-4. Conclusion: Findings related to Flt3 ligand, GM-CSF, and IL-4 are consistent with the international literature. Results from the present study are partly confirmative and partly hypothesis generating.

Plasma Concentration of Irisin and Brain-Derived-Neurotrophic Factor and Their Association With the Level of Erythrocyte Adenine Nucleotides in Response to Long-Term Endurance Training at Rest and After a Single Bout of Exercise.

The study aimed to assess the effect of a single bout of incremental exercise on irisin and BDNF plasma concentrations as related to erythrocyte purine nucleotides concentration at rest and after exercise. Master endurance master athletes (training experience 38 ± 6 years) and a group of untrained participants completed a single bout of progressive incremental exercise test until exhaustion. The dual-energy x-ray absorptiometry and blood collection were performed. Blood was taken twice at rest and 10 min after exercise. Concentrations of ATP, ADP, and AMP were assessed in the erythrocytes. Hypoxanthine and uric acid were determined in plasma using the high-performance liquid chromatography. Plasma concentrations of irisin and BDNF were assessed through the immunoenzymatic method. The ATP level, ATP/ADP ratio and AEC value were significantly higher in the athletic group. A significantly higher concentration of BDNF was it also noted in the trained group that correlated with the erythrocyte energy status at rest. The single session of exercise induced a significant increase in ATP erythrocyte levels in both groups. Both exerkines significantly correlated at rest with red blood cell adenine nucleotides and degradation products (BDNF positively and irisin negatively). The blood concentration of BDNF and irisin, in response to exercise, was not significantly different between groups. Obtained data revealed a higher erythrocyte energy status and lower purine degradation products concentration in master athletes. Also resting plasma exerkines differed substantially between groups. In conclusion, long-term training resulted in exercise adaptation reflected by a higher erythrocyte energy status, lower purine degradation products concentration and modified concentration of exerkines (higher BDNF and lower irisin blood concentrations). Therefore, we consider the training-induced adaptations in master athletes to be beneficial and significant. The moderate level of physical activity in the untrained group, even if sufficient in terms of general health, did not cause any discernible changes.

Advances in the treatment of hepatocellular carcinoma using drug-eluting beads

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor. Although radical surgery and liver transplantation are possible cures for the disease, most patients are beyond the optimum stage for radical treatment at the time of diagnosis. Transarterial chemoembolization (TACE) is the first choice of treatment for advanced HCC. Owing to the widespread use of conventional TACE (cTACE), the problems with this treatment cannot be ignored. Drug-eluting beads (DEBs), a new type of embolization material, appear to overcome the problems of cTACE, and they have other advantages such as synchronous controlled continuous drug release after chemotherapy and embolization and low blood concentrations after treatment. This review summarizes the recent advances in the use of DEB-TACE to treat HCC.

Trace element and vitamin deficiency: quantum medicine or essential prescription?

In critical care, micronutrients remain perceived as 'quantum' part, that is, a little pertinent component of therapy. Some micronutrients have attracted more attention because of their antioxidant properties. During the last decade, some large size trials have tested their therapeutic potential, generally as 'single high-dose micronutrient intervention', with variable success. This review aims at taking stock of most recent. Micronutrient blood levels are generally low in ICU patients, which has prompted the concept of replenishing or compensating deficits, or even realizing a pharmacological action. Single micronutrient trials have been conducted in large cohorts with selenium (≥1000 μg/day), with limited success but no harm. Other trials have tested high-dose vitamin D (>400 000 IU), with nonconvincing results despite selecting patients with very low blood levels. High-dose vitamin C has been tested in septic shock (+/- thiamine, hydrocortisone) with variable results. A problem encountered in all studies is definition of deficiency based on blood levels as majority of the patients suffer inflammation, which causes redistribution of the micronutrients away from the circulating compartment in the absence of real deficiency. Micronutrients are essential in the ICU. Due to their antioxidant properties and to the high prevalence of low blood concentrations suggestive of deficiency, several large-size RCTs have been conducted with variable success. Further research must clarify the respective importance of deficiency and inflammation.

P1100IMPACT OF THE RELATIONSHIP BETWEEN LOW MOLECULAR WEIGHT PROTEINS REMOVAL EFFICIENCIES AND THE VOLUME OF ALBUMIN LEAKAGE IN HEMODIAFILTRATION THERAPY

Abstract Background and Aims The purpose of hemodiafiltration (HDF) is to remove small- to large molecular weight solutes in order to prevent and treat complications and to improve the prognosis of dialysis patients. Especially, larger low molecular weight proteins (LMWPs) must be removed efficiently. β2-microglobulin (MG) (molecular weight [MW], 11.8 kDa: Stokes radius, 15.6A), is considered as an important marker of dialysis efficiency. However, MW of β2-MG is too small as a marker in HDF. Conversely, α1-MG (MW, 33 kDa: Stokes radius, 28.4A) is the most appropriate marker for evaluation of solute removal efficiency of HDF because of the following reasons: (1) optical molecular size; (2) not very low physiological blood concentration; (3) stable production rate; (4) removal by convection; and (5) accumulation in ESRD. Efficient removal of α1-MG without losing albumin (Alb) (MW,66 kDa: Stokes radius, 35.5A) is impossible even by HDF. In this study, we investigated the relationship between LMWP removal efficiencies and the volume of Alb leakage by analyzing the results of patients undergoing HDF. And we also evaluated the trend of the serum levels of patients who had received high-efficiency HDF for more than three years Method Eighty-seven patients who had received HDF in 2018–2019 were included. The results of HDF (a total of 435 sessions) were analyzed (blood flow rate, 261.5±28.5 mL/min; replacement fluid volume, 48.7 L/s pre-dilution on-line HDF and 14.2 L/s post-dilution on-line HDF). The removal efficiencies of β2-MG, prolactin (PRL), and α1-MG, and the volume of Alb leakage were examined. In addition, the relationship between the removal efficiency of each solute and the volume of Alb leakage was investigated. Changes in serum Alb level were analyzed in 13 patients who continued to receive high-efficiency HDF (the removal rate of α1-MG was 30% or more) for more than three years. Results Analysis of the results (mean ± SD) obtained from a total of 435 sessions (87 patients) showed that the removal rates of β2-MG, PRL, and α1-MG were 80.7 ± 4.5%, 75.8±9.4 and 33.8 ± 9.4%, respectively, and the Alb leakage was 3.9 ± 1.8 g/s. The equations of the approximate curve between Alb leakage and β2-MG, PRL, and α1-MG removal rates were expressed as follows: ï½™= 1.4197ln(x) + 78.972 (R2 = 0.0426), y = 9.7185ln(x) + 64.134 (R2 =0.4632), and ï½™™= 11.225ln(x) + 20.282 (R2 = 0.6191), respectively. These results indicate that the dynamics between Alb leakage and α1-MG removal are very similar. That is, although the molecular weight of Alb is twice as that of α1-MG, the difference in their Stokes radius is 20%; therefore, separate removal of Alb and α1-MG is impossible. The mean serum Alb level in 13 patients who received high-efficiency HDF for 3 years or longer was 3.59 ± 0.23 g/dL in January 2017 and 3.69 ± 0.28 g/dL in December 2019, revealing no changes. Conclusion The efficient removal of larger LMWPs leads to the leakage of Alb. However, an Alb leakage of 3 to 6 g/s has little influence on the serum Alb level of patients. Thus, α1-MG is the most appropriate marker of the solute removal efficiency of HDF.

Efficacy and Safety of LCP-Tacrolimus (Envarsus XR®) Conversion Therapy in Heart Transplantation

Little is known about the usefulness of LCP-tacrolimus (LCPT, Envarsus XR®) in heart transplantation. Tacrolimus-based immunosuppression use is limited by neurologic adverse reactions and consequent difficulty in titration of drug doses to therapeutic targets. LCPT offers improved bioavailability and lower peak blood concentrations which may lead to fewer neurological adverse effects while allowing for adequate therapeutic trough level titration. We aimed to evaluate outcomes in patients who were transitioned from immediate-release (IR) tacrolimus to LCPT. In this retrospective, single center analysis (1/2015-7/2019), 84 patients were transplanted, and 17 were converted to LCPT, predominantly for neurological adverse events (n=9) or failure to achieve a therapeutic drug level with IR tacrolimus (n=4) or both (n=4). Patients were followed for improvement in symptoms, rates of rejection and renal function. IR tacrolimus was converted to LCPT early post-transplant (median 1 month; 0.5-11 months). Median equivalent dose conversion ratio was 0.77 (LCPT/IR Tacrolimus). Dose stability trend was better with LCPT, which required 1.5 dose changes per month on average as compared to 3.0 changes for IR tacrolimus (range: 0-6.7 vs 0-8.0, respectively, p=0.07). Among 13/17 patients transitioned for neurotoxicity, 8 reported improvement in symptoms, 4 no improvement, and 1 worsening symptoms. In 7 patients, peak levels were checked (2-3 hours post dose) prior to conversion and were not excessively elevated (median 18.1; 15.5-33.4 ng/mL); six of these reported improvement in tremors or headaches after conversion despite moderate peak levels. ISHLT grade ≥ 2R rejections were infrequent and occurred in 1 patient on LCPT after intentional lowering of immunosuppression in the setting of invasive fungal infection. LCPT was associated with worsening renal function with median serum creatinine 0.99 mg/dL prior to conversion and 1.56 mg/dL after conversion (p=0.002). LCPT conversion therapy in heart transplantation allows maintenance of therapeutic drug levels in those difficult to achieve with IR tacrolimus and is associated with improved neurological symptoms and low rates of allograft rejection. However, significant concerns remain with regard to worsening renal function.

Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules.

HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA.

Poor outcome with anti-programmed death-ligand 1 (PD-L1) antibody due to poor pharmacokinetic properties in PD-1/PD-L1 blockade-sensitive mouse models

BackgroundRecently, antiprogrammed cell death protein 1 (aPD-1) and antiprogrammed death-ligand 1 (aPD-L1) monoclonal antibodies (mAbs) have been approved. Even though aPD-1 and aPD-L1 mAbs target the same PD-1/PD-L1 axis, it...

Pharmacokinetic Evaluation of 99mTc-radiolabeled Solid Lipid Nanoparticles and Chitosan Coated Solid Lipid Nanoparticles.

Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of 99mTc-labeled SLNs and chitosan modified SLNs in mice. 99mTc-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (99mTc-SLNs) and radiolabeled chitosan-coated SLNs (99mTc-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS). 99mTc-oxine with high radiochemical purity (RCP~100%) and stability (RCP > 97% at 24 h) was used to provide 99mTc-SLNs and 99mTc-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest 99mTc- SLNs susceptibility to aggregation. To that end, the main portion of 99mTc-SLNs radioactivity accumulates in the liver and intestines, while 99mTc-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of 99mTc-Chi-SLNs was higher than that of 99mTc-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. 99mTc- Chi-SLNs uptake in the kidneys in comparison with 99mTc-SLNs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h. The chitosan layer on the surface of 99mTc-Chi-SLNs reduces lipophilicity in comparison with 99mTc- SLNs. Therefore, 99mTc-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration.

Microbiome applications for pathology: challenges of low microbial biomass samples during diagnostic testing.

The human microbiome can play key roles in disease, and diagnostic testing will soon have the ability to examine these roles in the context of clinical applications. Currently, most diagnostic testing in pathology applications focuses on a small number of disease‐causing microbes and dismisses the whole microbial community that causes or is modulated by disease. Microbiome modifications have already provided clinically relevant insights in gut and oral diseases, such as irritable bowel disease, but there are currently limitations when clinically examining microbiomes outside of these body sites. This is critical, as the majority of microbial samples used in pathology originate from body sites that contain low concentrations of microbial DNA, including skin, tissue, blood, and urine. These samples, also known as low microbial biomass samples, are difficult to examine without careful consideration and precautions to mitigate contamination and biases. Here, we present the limitations when analysing low microbial biomass samples using current protocols and techniques and highlight the advantages that microbiome testing can offer diagnostics in the future, if the proper precautions are implemented. Specifically, we discuss the sources of contamination and biases that may result in false assessments for these sample types. Finally, we provide recommendations to mitigate contamination and biases from low microbial biomass samples during diagnostic testing, which will be especially important to effectively diagnose and treat patients using microbiome analyses.

Do Creatinine Blood Levels Act upon Fatty Acid Metabolites in Human Red Blood Cell Membranes?

Objectives: The aim of the present research is to correlate creatininemia and uricemia to HNE and MDA levels of Red Blood Cell purified membranes in comparison to those of normal subjects to characterize the effects of oxidative stress. Methods: The studied population consisted of 10 patients with endogenous both hypercreatininemic hyperuricemic and ten normal subjects. The measurement of total proteins in RBC ghosts and HNE and MDA are conducted on blood samples of patients. Results: The obtained data evidence that both creatinine and uric acid levels have influence on the ratio of both MDA/protein and HNE/protein content on RBC ghosts, demonstrating their possible protective role against oxidative stress at low concentrations in blood and oxidizing power at higher concentrations. Conclusion: The displayed results in this study suggest that at low concentrations of creatinine and uric acid there is oxidative stress in human erythrocyte membrane, but if creatinine and uric acid have slowed down to sufficient limits there is also oxidative stress, as demonstrated by MDA and HNE levels; only if the concentration of these two substances overwhelms a threshold.

Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice.

To analyse mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis. Mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis were analysed in four patients from the French Named Patient Programme by the French National Reference Centre for Herpesviruses. Of three absolute resistance cases, two were associated with treatment interruption or low letermovir concentrations in blood. A fourth case of breakthrough was not associated with resistance. Next-generation sequencing (NGS) genotyping confirmed rapid emergence of resistant mutants, within 3 months of treatment initiation. Measurement of letermovir concentration and genotyping should be recommended for patient follow-up during letermovir therapy.

Influence of secondary hyperparathyroidism in management anemia in patients on regular hemodialysis

Background/Aim. Anemia is a common complication in hemodialysis patients. Treatment of anemia is affected by iron deficiency, insufficient dose of erythropoietin, microinflammation, vitamin D deficiency, increased intact parathyroid hormone concentration and inadequate hemodialysis. The aim of the study was to determine the prevalence of vitamin D deficiency and its impact on hemoglobin con-centration, iron status, microinflammation, malnutrition, dialysis adequacy and erythropoietin dose in patients on regular hemodialysis. Methods. The study involved 120 patients divided into three groups: severely deficient of vitamin D: 25- hydroxyvitamin D[25(OH)D] < 10 ng/mL; deficient ? 25(OH)D within range of 10?20 ng/mL, and insufficient ? 25(OH)D > 20 ng/mL. For statistical analysis Kolmogorov- Smirnov test, the single-factor parametric analysis of variance ? ANOVA and Kruskal-Wallis test were used. Results. The prevalence of vitamin D deficiency in patients on regular hemodialysis was 75.83%, while the prevalence of severe vitamin D deficiency was 24.7%. Patients with severe vitamin D deficiency had lower blood concentration of hemoglobin, hematocrit, serum concentration of total proteins and albumin, and dialysis indices were also lower compared to the other two groups of patients. The level of C-reactive protein was significantly higher in the group of patients with severe vitamin D deficiency than in the two rest groups. Conclusion. Hemodialysis patients with severe vitamin D deficiency have lower hemoglobin, lower dialysis adequacy, significant microinflammation, malnutrition, bone metabolism disorders and need higher dose of erythropoietin than patients whose vitamin D was higher than 10 ng/mL. Vitamin D is important risk factor for development of anemia in hemodialysis patients and important factor that can affect treatment of anemia in these patients.

Safety of Use of Tantalum in Total Hip Arthroplasty.

Tantalum implants have been used in >500,000 orthopaedic patients. Although the risks of metallosis and aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) after total hip arthroplasty (THA) are being debated, we are not aware of any studies investigating the liberation of tantalum ions and their potential effects on the immune system. We evaluated whether tantalum concentrations are elevated after THA with acetabular tantalum implants and assessed potential alterations in T-cell subpopulations. After a mean follow-up of 4 years (range, 0.5 to 8.9 years) of 144 patients who had undergone THA, blood samples were analyzed regarding blood tantalum concentrations, total white blood-cell counts, and lymphocyte subsets in 3 groups of patients: those treated with non-tantalum primary THA ("primary non-tantalum," n = 30), those treated with primary THA with a tantalum cup ("primary tantalum," n = 30), and those who underwent revision surgery with a tantalum shell ("revision tantalum," n = 84). Blood donors served as controls for immunological parameters (n = 59). Correlations between tantalum concentrations and human leukocyte antigen (HLA)-DR T cells were calculated, radiographic signs of implant loosening were assessed, and the Harris hip score (HHS) was used to evaluate hip function. The median tantalum concentration was similar to the detection limit both in the primary non-tantalum group (0.05 µg/L, 95% confidence interval [CI] = 0.05 to 0.05 µg/L) and in the primary tantalum group (0.051 µg/L, 95% CI = 0.050 to 0.055 µg/L), and it was 0.091 µg/L (95% CI = 0.083 to 0.112 µg/L) in the revision tantalum group (p < 0.0001 in the group-wise comparison with both primary non-tantalum and primary tantalum). We found a weak negative correlation of higher tantalum concentration with the concentration of HLA-DR/CD8 T cells (r = -0.22, 95% CI = -0.35 to -0.05, p = 0.01) but no correlation of tantalum concentration with the concentration of HLA-DR/CD4 T cells (r = -0.11, 95% CI = -0.27 to 0.06, p = 0.24). The values for all lymphocyte subgroups were within normal ranges. No implants were deemed loose. The median HHS was good to excellent. Exposure to stable tantalum cups is associated with low blood concentrations of tantalum. Signs of T-cell activation typical of ALVAL seem to be lacking. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Vegetarian Diet during Pregnancy Is Not Associated with Poorer Cognitive Performance in Children at Age 6-7 Years.

Compared with omnivorous mothers, vegetarian mothers have lower intakes of some nutrients required for neurological development. However, there is a lack of information about the impact of vegetarianism during pregnancy on subsequent cognitive function in children. The aim of this study was to investigate whether vegetarianism during pregnancy is associated with altered maternal nutritional status and with cognitive function in children at six to seven years of age. Women aged 20–34 years participating in a prospective observational study who provided dietary data and blood samples in early pregnancy (11 weeks; 78 vegetarians and 2144 omnivores) or late pregnancy (34 weeks; 91 vegetarians and 2552 omnivores). Compared with omnivorous women, vegetarian women had lower blood concentrations of arachidonic acid, docosahexaenoic acid, and cobalamin in early and late pregnancy. Vegetarianism in pregnancy was linked to higher maternal educational attainment, longer breastfeeding duration, lower incidence of smoking during pregnancy and a tendency towards higher IQ in the mothers. Concentrations of some nutrients required for neurodevelopment were lower in maternal blood during gestation; however, after controlling for confounders consuming a vegetarian diet during pregnancy was not associated with poorer neurocognitive development of the children in this study.

Biomonitoring of concentrations of polycyclic aromatic hydrocarbons in blood and urine of children at playgrounds within Owerri, Imo State, Nigeria.

Polycyclic aromatic hydrocarbons (PAHs) exposure is among the leading air pollutants associated with diverse adverse health effects due to their persistent, bio-accumulative and toxic characteristics. Children are most affected by these pollutants, yet studies directly related children to these pollutants are scarce in Nigeria. In this study, blood and urine from 36 children between the ages 4-14 years were collected as per sterile procedures by a licensed phlebotomist from the antecubital fossa into BD vacutainer tubes® while a mid-stream urine sample into acid-washed 120 mL BD vacutainer urine cups and stored in refrigerator at –4˚C for 6 hours, then each 5 mL was extracted with 10 mL of pentane and analyzed for 15 PAHs using GC-MS. Results revealed that PAHs concentrations (53.48 to 70.8 μg/dL) in blood was lower than in urine (94.98 to 115.04 μg/dL). Mean values had no significant (p>0.5) differences between schools, possibly due to the fact that all schools were experiencing similar anthropogenic disturbances. At 5% level of significance, positive and strong correlationships (r=0.83, r=0.73) were observed for fluorene-fluoranthene (FLa) and benzo (a) anthracene-FLa respectively in blood samples. Two and three rings PAHs had generally low concentrations in both blood and urine. Despite being the most distributed compound, the concentration of dibenzo (a,h) anthracene was highest for urine than in blood. Urine PAHs showed higher concentration of carcinogenic PAHs than blood. Elimination ratios (ER) such as for acenaphthene (0.06) and anthracene (Ant; 0.11) were considered low while values such as for FLa (1.36) and indeno [1, 2, 3-cd] pyrene (1.55) were considered high ER. Trends in elimination ratios showed close similarity. In conclusion there was elevated PAHs in blood and urine of children with consequent high carcinogenic and then non-carcinogenic risks. This research is significant in setting the stage for more detailed work at same time alerting policy makers on the need for urgent mitigation steps that will reduce children exposure to this class of dangerous pollutants.

Sensitive electrochemical aptasensor for detecting EpCAM with silica nanoparticles and quantum dots for signal amplification

The epithelial cell adhesion molecule (EpCAM) is a known biomarker of circulating tumor cells that plays an important role in tumor metastasis. The detection of EpCAM is vital for personalized diagnosis and therapy but is challenging because of its extremely low concentration in peripheral blood. In our work, an electrochemical aptasensor has been developed to quantitatively detect EpCAM at low concentrations. A gold electrode modified with an aptamer can capture EpCAM, which can then be further recognized by a second aptamer acting as a signal reporter. To amplify the signal, a silica nanoparticle/CdSe complex has been designed to enhance the detection system. First, silica nanoparticles were synthesized to act as carriers for loading many CdSe quantum dots which are capable of binding with the second aptamer by biotin-streptavidin interactions. A molecule of EpCAM can bind with numerous CdSe quantum dots (QDs) to realize significant signal amplification. By stripping square wave voltammetry (SSWV), concentrations down to 10 aM EpCAM can be successfully detected and quantified based on the newly developed aptasensor. The detection linear range is from 10 aM to 100 pM. This principle can also be extended to other biomarkers when a suitable aptamer or antibody is available. This aptasensor is expected to be a potential tool for the diagnosis, therapeutic evaluation and personalized medical care of cancer patients.

The relationship between vitamin D deficiency and oxidative stress can be independent of age and gender.

The active vitamin D (1,25(OH)2D) acts through a nuclear receptor to perform several functions in cellular metabolism. 1,25(OH)2D participates directly in calcium homeostasis, regulates the immune system, nervous system, blood pressure, insulin secretion, among others. Vitamin D deficiency could also be associated with several diseases and increased cellular oxidative damage. The present study aimed to investigate whether lipid peroxidation and/or protein oxidation are affected by vitamin D deficiency and whether sunlight exposure/diet, gender, and age might influence this relationship. Vitamin D concentrations were obtained from the Heart Hospital database and a questionnaire was applied among the 212 participants. We used the inactive vitamin D (25(OH)2) in the analyses since 1,25(OH)2D has a short half-life and a low blood concentration. Lipid peroxidation and protein oxidation analyses were performed using spectrophotometry. Multivariate analyses suggested the participation of vitamin D deficiency (<30ng/mL) and sunlight/diet in oxidative stress (p <0.05; R2 MDA: 0.562; R2 CG: 0.429). Multiple linear regression test show that the age and gender of patients are not interfering in the analyses (p>0.05). Therefore, we suggest that the relationship between vitamin D deficiency and oxidative stress can be independent of age and gender.

Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort.

BackgroundPreeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort.Methods and ResultsA total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (PRs) and 95% CIs. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose–response trend for Mn (P for trend<0.001) and to some extent for Cd (P for trend=0.009) quintiles. After multivariable adjustment, a 1 SD increment in Mn was associated with 32% lower risk of developing preeclampsia (PR=0.68; 95% CI, 0.54–0.86), whereas a 1 SD increment in Cd was associated with 15% higher risk of preeclampsia (PR=1.15; 95% CI, 0.98–1.36). Null associations were observed for Se, Pb, and Hg.ConclusionsFindings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.

Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy.

BackgroundDiabetic retinopathy (DR) is a complication of diabetes that affects the eyes and vision. It is a leading cause of visual impairment and blindness in working-age people. Vascular endothelial growth factor-A (VEGF-A) is a primary initiator and potential mediator of DR. Matrix metalloproteinase-9 (MMP-9) plays a progressive role in the onset and severity of DR. Interleukin-12 (IL-12) is a cytokine of the chemokine family that could reduce the levels of MMP-9 and VEGF-A and suppress tumor angiogenesis. We hypothesize that IL-12 may also have superior therapeutic efficacy against DR. However, protein drugs are prone to degradation by various proteases after drug injection. Therefore, they have short half-lives and low blood concentrations. The objective of this study was to develop IL-12-loaded nanoparticles for long-term and sustained DR treatment.MethodsIL-12-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IL-12-PNP) were developed by double emulsion. The characteristics, anti-DR activity, and mechanisms of IL-12-PNP were examined in vitro and in vivo.ResultsThe nanoparticles had suitable particle size (~132.8 nm), drug encapsulation efficiency (~34.7%), and sustained drug release profile. Compared with IL-12 and blank nanoparticles, IL-12-PNP showed better inhibitory efficacy against VEGF-A and MMP-9 expression in rat endothelial cells and DR mouse retina. Intraocular IL-12-PNP administration significantly reduced retinal damage in DR mice as they presented with increased thickness and decreased neovascularization after treatment.ConclusionThese data indicate that IL-12-PNP is an effective drug delivery platform for DR therapy. It restores the thickness and reduces neovascularization of the retinas of DR mice.