Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution.

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats' general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD-0.67 ± 0.12; 1/5 MAD-0.59 ± 0.07; 1/10 MAD-0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels.

In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography.

In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/ß-K6P2W18O62 (WD-POM) exhibits superior performance as a computed tomography (CT) contrast agent, in comparison to the standard contrast agent iohexol. A toxicity evaluation of WD-POM was performed according to standard toxicological protocols using Wistar albino rats. The maximum tolerable dose (MTD) of 2000 mg/kg was initially determined after oral WD-POM application. The acute intravenous toxicity of single WD-POM doses (1/3, 1/5, and 1/10 MTD), which are at least fifty times higher than the typically used dose (0.015 mmol W kg-1) of tungsten-based contrast agents, was evaluated for 14 days. The results of arterial blood gas analysis, CO-oximetry status, electrolyte and lactate levels for 1/10 MTD group (80% survival rate) indicated the mixed respiratory and metabolic acidosis. The highest deposition of WD-POM (0.6 ppm tungsten) was found in the kidney, followed by liver (0.15 ppm tungsten), for which the histological analysis revealed morphological irregularities, although the renal function parameters (creatinine and BUN levels) were within the physiological range. This study is the first and important step in evaluating side effects of polyoxometalate nanoclusters, which in recent years have shown a large potential as therapeutics and contrast agents.

Magnesium supplementation and iron status among female students: The intervention study.

Background: Literature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants. Methods: One hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxyand oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters. Results: A statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days. Conclusions: Mg supplementation leads to an improvement in the certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.

Correlation of Ionized Magnesium with the Parameters of Oxidative Stress as Potential Biomarkers in Patients with Anxiety and Depression: A Pilot Study.

Background: Magnesium (Mg) is the second most abundant intracellular cation. Ionized Mg is the only active form of Mg. The concentration of ionized Mg could be a potentially novel biomarker for anxiety and depression. Aim: The aim of this study was to assess the serum concentration of ionized Mg and its correlation with biomarkers of oxidative stress and inflammation in patients with anxiety and depression. Methods: In this study included 93 respondents were divided into 3 groups: C (control group-18 respondents); A (patients with anxiety disorder, dissociative/conversion disorders and somatoform disorders-36 patients); D (patients with depression-39 patients). Clinical diagnosis was based on ICD-10 criteria. Blood samples were used for standard laboratory analysis, ionized Mg analysis, oxidative stress, and inflammatory parameters. Results: Statistical significance was recorded between healthy volunteers and patients (anxiety/depression) in ionized Mg values. In anxious patients, malondialdehyde (MDA) had a positive correlation between the parameters of oxidative stress with ionized Mg. In depressive patients, MDA had a positive correlation, and glutathione peroxidase 1 (GPX1) a negative correlation with the concentration of ionized Mg. Conclusion: Ionized Mg and its correlation with parameters of oxidative stress could be potential biomarkers in anxious and depressive patients.

Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels.

This study aimed to investigate the short-term effects of three magnesium (Mg) dietary supplements containing mineral immediately available for absorption on Mg biochemical status indices (ionized and total Mg), as well as their effects on electrolytes levels in healthy female young adults (n = 61). After a 10-days intervention period supplementation with powder/granulate containing Mg oxide led to an increase in both ionized Mg concentration and % in total Mg in comparison with the baseline. Supplementation with Mg citrate was associated with the significant increase in % of ionized fraction and decrease in serum total Mg concentration. By contrast, among participants consuming Mg carbonate in the form of effervescent tablets ionized Mg concentration and % in total Mg decreased, without detectable changes in serum total Mg. In conclusion, after the short-term supplementation period, Mg oxide demonstrated superior bioavailability compared to the other examined Mg supplements without affecting other minerals' levels.

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system.

In this study, the in vivo hypoglycemic effect of a donut-shaped polyanion salt (NH4)14[Na@P5W30O110]·31H2O {NaP5W30} and its Ag-containing derivative K14[Ag@P5W30O110]·22H2O·6KCl {AgP5W30}, as well as their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study, Wistar albino rats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5, 10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels, measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studied compounds induced the most pronounced and time dependent glucose lowering effects at the doses of 20 mg kg-1. Thus, daily doses of 20 mg kg-1 were administered to Wistar albino rats orally for 14 days in further toxicity examinations. The serum glucose concentration and biochemical parameters of kidney and liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14 days after the polyoxotungstate administration. Both investigated compounds did not induce statistically significant alterations of the serum glucose and uric acid concentrations, as well as some of the liver function markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities). However, the significant decrease in serum total protein and albumin concentrations and the increase in biochemical parameters of renal function - serum urea (up to 63.1%) and creatinine concentrations (up to 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changes were in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic and nephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.

Faecal Occult Blood Point-of-Care Tests.

BACKGROUND: Early detection of colorectal cancer decreases the risk of mortality. Faecal occult blood tests (FOBT) are recognised as a useful tool for colorectal cancer screening. These non-invasive, rapid, and easy-to-carry assays are very often used as a point-of-care test and for self-testing. On the market, there are various types of FOB tests available, including chemical and immunochromatographic tests, which are based on different detection methods and differ in their sensitivity and specificity. CONCLUSIONS: Clinicians should be aware of the causes of false-negative and false-positive test results, which can vary depending on the test. Additionally, stool sampling bias may be a source of error and must be considered by the clinician. The current FOBT methods are subject to various interfering factors; items such as proper preparation of the patient prior to testing or the clinician's knowledge of testing limitations are key in correct interpreting results. Novel technologies such as FOBT DNA tests, micro RNA tests, and biochips equipped with bacteria can indicate bleeding from the gastrointestinal tract and improve diagnostics process.

Biochemical Markers of Renal Function.

Kidney damage can be induced by ischemia, autoimmune diseases, hypertension, allograft rejection, metabolic or genetic disorders, infections or toxins. The influence of these factors could result in acute kidney injury (AKI) defined as an unexpected decrease in urine output or renal function, or encourage the development of chronic kidney disease (CKD). Biomarkers of renal function, measured in urine and serum, are in increasing use in order to estimate the severity and nature of kidney injury, and consequently apply appropriate therapy and improve patient management. The determined values of biomarkers can suggest the potential risk of kidney disease and the type of renal injury, predict the disease progression, as well as be helpful for assessing the response to an applied therapy. Although novel biomarkers are in practical use, serum creatinine, the indicator of glomerular filtration rate is still the most frequently used biomarker of renal function despite its known limitations. In recent decades, numerous studies resulted in discovering urinary and serum proteins that can serve as biomarkers for early and accurate detection of AKI and its development, as well as the identification of CKD. This review gives an overview of the most important renal biomarkers investigated in kidney diseases, classified in following types: functional biomarkers, up-regulated proteins, enzymes, and cycle arrest biomarkers. It describes their properties, physiological roles, and discusses the utility of these molecules in different clinical settings.

Indirect estimation of reference intervals for thyroid parameters.

BACKGROUND: The aim of this work was to determine indirect reference intervals from patients' results obtained during routine laboratory work. This could be an accurate alternative to the laborious and expensive job of producing reference intervals for populations according to international recommendations. METHODS: All the results for thyrotropin (TSH), total and free thyroxine, and triiodothyronine (T4, fT4, T3, and fT3) stored in our laboratory information system between 2008 and 2011 were included in this study. We used logarithmic transformation of the raw data to exclude outliers. After visual observation of the data distribution, we estimated non-parametric reference intervals. A standard normal deviation test was performed to test the significance of differences between subgroups. RESULTS: There was no significant difference in the serum levels of the analyzed thyroid parameters, so we calculated combined reference values. However, we found a significant difference in TSH values between ambulatory and hospitalized patients, but only in 2011. Indirect reference values for TSH, T4, fT4, T3 and fT3 were 0.42 - 3.67 mIU/L, 66.0 - 136.10 nmol/L, 10.20 - 18.40 pmol/L, 1.10 - 2.39 nmol/L, and 3.17 - 5.59 pmol/L, respectively. CONCLUSIONS: The indirect determination of laboratory-specific reference intervals using patients' laboratory data is a relatively easy and inexpensive method. Also, indirect reference limits will be more precise and true if skewness and kurtosis of the distribution are not too large.

Indirect estimation of age-related reference limits of thyroid parameters: a cross-sectional study of outpatients' results.

OBJECTIVES: Defining adequate reference limits (RLs) for thyroid hormones is an important task for support monitoring and the treatment of subclinical thyroid disease. We determined whether there are age-related RLs for thyroid parameters in male and female outpatients free of overt thyroid disease. DESIGN: We analyzed 22,860 results (11,440 male and 11,420 female outpatients above the age of 18) for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that were stored in our laboratory information system between 2008 and 2011. We calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters. RESULTS: Our results indicate higher TSH levels with ageing, with a significant difference (p < 0.05) between the 97.5th centiles for males and females older than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9 pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect estimates of the 97.5th centiles for TSH for males and females were not significantly different and were below the generally recommended upper limit (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically significant change in mean T3 values in the analyzed population. CONCLUSIONS: This cross-sectional study indicates change in TSH and fT4 levels with ageing and gender-related upper limits. This suggests that by using indirect estimation a laboratory could provide clinicians with more accurate gender- and age-specific RLs for thyroid parameters.

Magnesium, aging, and the elderly patient.

Magnesium, beyond any doubt, plays an important role in metabolism. Alterations of magnesium levels have an impact on many organs and systems, especially during aging. We had 156 participants aged 60-93 years (average 74.7 years) in our survey. Of them, 49 were men and 107 were women. Treatment with loop diuretics (Furosemid and Bumetanide) and magnesium levels was correlated, as well as the influence of magnesium levels on life span. Serum magnesium levels were measured in patients receiving diuretics and in the control group. Also, magnesium levels were measured in patients who passed away in the course of their disease and were compared with the control group. Magnesium levels in the diuretic group (100 patients) were 0.93 +/- 0.094 mmol/l, while the average levels in the control group of 56 patients were 0.89 +/- 0.075 mmol/l. In 29 patients who passed away, average magnesium levels were 0.92 +/- 0.078 mmol/l, while in the control group (127 patients), magnesium levels were 0.93 +/- 0.083 mmol/l. The differences were not statistically significant. There were no differences in serum magnesium of the elderly persons investigated regarding age group, gender, or type of diuretics. If methods of determining ionizing magnesium in serum or intracellular magnesium are not available, normal magnesium values in the serum are to be taken with a qualified acceptance.