Serum levels of proinflammatory cytokines and selected bioelements in perimenopausal women with regard to body mass index.

During the menopause, decreased estrogen levels may be accompanied by increased levels of inflammatory mediators. Many studies also show significant relationships between the levels of bioelements and proinflammatory cytokines. The aim of this study was to assess the levels of proinflammatory cytokines, C-reactive protein (CRP), and selected bioelements in perimenopausal women with regard to BMI. METHODS: The study of 217 perimenopausal women involved the completion of questionnaires concerning sociodemographic and medical data, anthropometric measurements, and blood collection. RESULTS: In all studied women, the levels of IL-1ß significantly positively correlated with Ca, Mg, and Sr; IFNγ significantly negatively correlated with Sr, and IL-6 with Mg. In women with a normal BMI, the levels of IL-1ß significantly positively correlated with Ca and Sr, and CRP positively correlated with Zn. In overweight women, the levels of IL-1ß positively correlated with Ca, IL-6 with Na, and IFNγ negatively correlated with Sr. In obese women, the levels of CRP positively correlated with Zn, TNFα with Mg, IFNγ with Cu and P. The levels of IL-6 negatively correlated with Ca and Mg. CONCLUSIONS: BMI may be one of the factors that affect the relationship between serum bioelement levels and the levels of proinflammatory cytokines and CRP in women, especially during the menopausal period.

Effect of a maximal exercise test on serum and urinary concentrations of magnesium, phosphorous, rubidium and strontium in athletes.

AIM: This study aims to determine the changes induced by a maximal exercise test until exhaustion on the serum and urinary concentrations of Magnesium (Mg), Phosphorous (P), Rubidium (Rb) and Strontium (Sr) in athletes (AG) and sedentary students (SG). METHODS: Fifty subjects participated in the study divided into two groups. In AG there were twenty-five male athletes and in SG there were twenty-five male sedentary students. Both groups performed an exercise test until exhaustion, starting at 8 or 10 km/h respectively, and increasing the speed at 1 km/h every 400 m. Serum and urine samples were obtained from all participants before and after the test. RESULTS: Regarding the basal status, AG showed lower values of Mg in serum (p < 0.05) and urine (p < 0.01), but higher concentrations of serum P (p < 0.05) in comparison to SG. Comparing the pre and post-test values, corrected or non-corrected for hemoconcentration in serum and for creatinine in urine, AG showed a decrease in serum Mg (p < 0.05), in serum P (p < 0.01) and in urinary Sr (p < 0.01) while an increase was observed in urinary P (p < 0.05) and in urinary Rb (p < 0.05). CONCLUSIONS: It can be concluded that a treadmill test until exhaustion leads to changes in serum and urinary concentrations of minerals in both AG and SG males. This may reflect an adaptive response of the body to overcome the physical stress and, in some cases, to avoid loss of these elements.

Lower strontium in two different body matrices in neurodevelopmental disorders: A preliminary report.

BACKGROUND: Environmental factors, including elemental homeostasis, have not been studied sufficiently in neurodevelopmental disorders (NDD). This study aims to compare the status of 13 elements in blood and deciduous teeth dentine of children having an autism spectrum disorder or attention deficit hyperactivity disorder with typically developing controls. METHODS: Elements including calcium, phosphorus, magnesium, iron, zinc, copper, chromium, manganese, mercury, lead, cadmium, molybdenum, and strontium in both deciduous teeth and blood were analyzed by inductively coupled plasma mass spectrometry. RESULTS: Strontium levels in both blood and teeth samples were found to be significantly lower in the NDD group. Additionally, blood cadmium and mercury levels, and copper/zinc ratio were higher in the NDD group. CONCLUSIONS: Our results warrant further investigation in a large series of NDD examining symptom levels and genetic variations associated with elemental homeostasis.

Circulating metal concentrations, inflammatory cytokines and gestational weight gain: Shanghai MCPC cohort.

OBJECTIVES: Based on a prospective birth cohort, we aimed to investigate the associations between maternal circulating metals exposure and gestational weight gain (GWG) across pregnancy, and explore whether maternal inflammatory cytokines could contribute to the GWG changes associated with metals exposure. METHODS: A total of 234 pregnant women from the Shanghai Maternal-Child Pairs cohort were enrolled in this panel study. 547 blood and serum samples were collected from pregnant women during three follow-up visits, and the circulating concentrations of 27 metals were determined by using the ICP-MS method. Five inflammatory cytokines in serum samples were measured through multiplexed immunoassays. The linear mixed models were used to estimate the association between each ln-transformed metal concentration and GWG across pregnancy. Robust generalized linear regression models were used to estimate the associations among circulating metals, GWG, and inflammatory cytokines. RESULTS: The GWG during pregnancy was 13.76 ± 1.40 kg. The concentrations Co, Zn, Mo, B, Ag and Te in second or third trimesters were significantly higher than those in early second trimester. The concentration of Mg decreased with the increase of pregnant weeks and no significant statistical differences were found in the concentrations of other metals in different trimesters. Among the detected 26 metals, Li and Sr concentrations were positively associated with GWG in the third trimester. The GWG increased by 0.100 kg (95% CI 0.005, 0.195) and 0.120 kg (95% CI 0.009, 0.232) with each one ln-concentration increase in circulating Li and Sr concentrations, respectively. Concentrations of Li and Sr in the third trimester were positively associated with tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6, but negatively associated with growth differentiation factor-15 (GDF-15) significantly. Besides, IL-6 and GDF-15 levels were associated with the increase or decrease of overall pregnancy GWG, respectively. CONCLUSIONS: Results showed that maternal exposure to Li and Sr were associated with increased GWG, in which maternal IL-6 and GDF-15 could contribute to the associations between metal exposures and GWG in pregnant women.

Strontium and antimony serum levels in healthy individuals living in high- and low-risk areas of esophageal cancer.

BACKGROUND: It has been shown there is an upward trend for strontium (Sr) and antimony (Sb) levels from low-risk (LR) to high-risk (HR) areas of etiology of esophageal cancer in water, soil, and grains grown in Golestan province. In the present study, the serum levels of Sr and Sb were determined in healthy individuals living in these areas. METHODS: This cross-sectional study was performed on fasting blood serum of adult healthy individuals collected by cluster sampling. Subjects were divided into two groups, those living in either HR or LR areas. Strontium and antimony serum levels were measured using a graphite furnace atomic absorption spectroscopy. RESULTS: A total of 200 volunteers were enrolled from which 96 persons (48%) and 104 persons (52%) were from either HR or LR areas, respectively. The sex distribution was 40.9% male and 59.1% female, and the average age of enrolled people was 50.9 years. The average strontium levels were 30.44 ± 4.05 and 30.29 ± 3.74 µg/L in LR and HR, respectively. It also has been shown the average antimony levels were 15.21 ± 3.40, 14.81 ± 3.17, 15.13 ± 3.62, and 15.07 ± 3.62 µg/L in LR, HR, urban, and rural populations, respectively. CONCLUSION: The serum levels of strontium and antimony were not significantly different in healthy adults living in high- and low-risk areas of esophageal cancer. However, the average antimony serum levels in Golestan Province were above the reference interval in different countries.

Association between plasma strontium, a bone-seeking element, and type 2 diabetes mellitus.

BACKGROUND & AIMS: Drinking water and food are the major sources of strontium in human. Strontium is essential for bone metabolism, while its role in glucose and lipid metabolism is largely unknown. We aimed to investigate the association of strontium, a bone-seeking element, with type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) and to further explore the potential mechanisms. METHODS: The case-control study included 1448 newly diagnosed T2DM patients, 782 IGR patients, and 2230 matched controls with normal glucose tolerance. Plasma strontium and other plasma minerals were quantified via inductively coupled plasma mass spectrometry. Multivariable logistic regression analysis was used to evaluate the independent associations between plasma strontium and T2DM and IGR. RESULTS: Plasma strontium was inversely associated with T2DM and IGR. After adjustment for sociodemographic, lifestyle factors, and multiple plasma metals, the odds ratios (95% confidence intervals) of T2DM and IGR were 0.45 (0.35-0.57) and 0.55 (0.43-0.71), respectively, comparing the highest to the lowest quartile of plasma strontium levels. In spline analysis, the odds of T2DM and IGR decreased remarkably with increasing strontium concentration and followed by a plateau. Additionally, plasma strontium was negatively associated with total cholesterol, low density lipoprotein cholesterol, and lipid peroxidation (plasma malondialdehyde level). CONCLUSIONS: The current study indicated that higher plasma strontium concentration was associated with lower odds of T2DM and IGR. Further studies are warranted to confirm these findings and to clarify the underlying mechanisms.

Increased serum strontium levels and altered oxidative stress status in early-onset preeclampsia.

BACKGROUND: Correctly distinguishing preeclampsia (PE), gestational hypertension (GH), and intrauterine growth retardation (IUGR) is a challenge for clinicians due to existing similarities. In our previous study, we showed that serum strontium (Sr) levels were elevated in preeclamptic women compared to healthy and GH pregnant women at the end of pregnancy. The main aim of this study was to evaluate Sr and oxidative stress in PE at the time of symptoms onset and before and compare it with IUGR/GH. METHODS: Samples collected at symptoms onset included 77 preeclamptic women and 72 women diagnosed with IUGR/GH divided into two groups according to the gestational extraction week (<34 and ≥ 34). Fifteen patients were also serialized until delivery. Samples collected before symptoms onset included 140 women who developed early-onset PE (E-PE, n = 9), late-onset PE (L-PE, n = 13), IUGR (n = 9), GH (n = 32) and no pathologies (n = 77). Strontium, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), uric acid (UA), creatinine, lipid peroxidation, and total antioxidant activity (TAA) were measured. RESULTS: Mean Sr, sFlt-1/PIGF ratio, UA, and lipid peroxidation/TAA ratio levels were significantly higher (p = 0.002, <0.0001, <0.0001 and = 0.03, respectively) and estimated glomerular filtration rate (eGFR) and TAA significantly lower (p = 0.0008 and < 0.0001, respectively) in E-PE vs other pathologies when gestational extraction week was <34. There was a significant correlation between Sr and eGFR (r = 0.43, p = 0.02), sFlt-1/PIGF ratio (r = 0.56, p = 0.002), TAA and gestational week of sampling (r = -0.45, p = 0.02) and UA (r = -0.82, p < 0.0001) in the E-PE serial samples. No differences were found in Sr levels before symptoms onset. CONCLUSION: Serum Sr concentration and oxidative status are increased in E-PE when compared to other pathologies at the time of symptoms onset. More studies are needed to elucidate the causes of Sr levels elevation and its role in the pathophysiology of PE.

The content of toxic and essential elements in trabecular and cortical femoral neck: a correlation with whole blood samples.

Pollution caused by heavy metals affects all forms of life. The aim of the study was to determine the content of toxic (Sr, Ni, Pb, V, Cd, U, Rb, As) and essential (Na, K, Ca, Mg, Zn, Cu, Se, Mn, Cr, Mo, Co) metals in the bone and whole blood samples, in regard to clinical means of long- and short-term exposure, respectively. For this purpose, the cortical and trabecular parts of femoral neck, as well as the blood samples, were collected to quantify bone-important metals by inductively coupled plasma (ICP)-based techniques. According to principal component analysis (PCA), the most influential metal discriminating blood samples was Cu, while all other quantified elements were present in higher amounts in the bones. Additionally, trabecular bones (TBs) could be characterized by higher content of Mo, Cr, V, Mn, Co, As, and Ni compared to cortical bones (CBs). Linear discrimination analysis (LDA) was successfully applied to distinguish trabecular bone from the cortical bone. Significant correlation between essential Ca and toxic Sr with other elements was found and discussed. This study provides novel data on the effects of metal pollutants on bone health hazards. The results obtained for investigating metals may serve as a baseline for further clinical investigations in the orthopedic fields.

Correlations between plasma strontium concentration, components of calcium and phosphate metabolism and renal function in type 2 diabetes mellitus.

BACKGROUND: Renal function decline in diabetic kidney disease is accompanied by calcium and phosphate metabolism alterations. Whereas strontium (Sr2+ ) has many similarities with calcium, little is known about Sr2+ in this respect. We studied the association of plasma Sr2+ concentration and parameters associated with an altered calcium and phosphate metabolism in diabetic kidney disease. MATERIALS AND METHODS: Plasma Sr2+ concentration was measured in 450 patients included in the DIAbetes and LifEstyle Cohort Twente-1. Patients were classified based on chronic kidney disease (CKD) stages: stages 1-2, stage 3 and stages 4-5 (estimated glomerular filtration rate of ≥60 mL·min-1 ·1.73 m-2 , 30-59 mL·min-1 ·1.73 m-2 and ≤29 mL·min-1 ·1.73 m-2 , respectively). The associations between log-transformed plasma Sr2+ concentration and parameters of calcium and phosphate metabolism were studied using multivariate linear regression analysis. RESULTS: Overall, median plasma Sr2+ concentration was in normal range, 269 nmol/L, but was progressively higher in patients with lower renal function, that is 246 nmol/L (CKD 1-2), 347 nmol/L (CKD 3) and 419 nmol/L (CKD 4-5). In multivariate analysis, independent associations were found between plasma Sr2+ concentration and both eGFR (ß = -0.401, P < 0.001) and plasma fibroblast growth factor 23 (FGF23) concentration (ß = 0.087, P = 0.04). CONCLUSIONS: We found an independent inverse association between eGFR and plasma Sr2+ concentration and an independent association between plasma Sr2+ concentration and plasma FGF23 concentration, a marker of deranged calcium and phosphate metabolism. Further research is needed to determine the mechanisms behind these associations and the impact of an elevation in plasma Sr2+ concentration on bone mineralization and calcification.

Strontium and its role in preeclampsia.

BACKGROUND: Preeclampsia (PE) is considered a specific vascular disease in which endothelial dysfunction may be the crucial factor of its pathogenesis. It has been suggested that strontium (Sr) may play a role in the pathophysiology of PE. Our group established in a previous study the serum levels of Sr in healthy pregnancies, and the main aim of the present study was to evaluate Sr concentrations and oxidative status in preeclamptic women. METHODS: The study population included women with early-onset PE (E-PE, n = 39), late-onset PE (L-PE, n = 67) and serial samples from a subset of preeclamptic women (PE-ss, n = 20). The control group included women with gestational hypertension (GH, n = 56) and healthy pregnancies (samples collected in the 1st (n = 50), 2nd (n = 51) and 3rd trimesters (n = 53)). Strontium, calcium (Ca), uric acid (UA), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), lipid peroxidation and total antioxidant activity (TAA) were measured in these samples. RESULTS: Mean Sr levels were significantly higher in PE than in control groups (p ≤ 0.0001). Calcium values were found to be significantly lower in E-PE compared to control groups (p = 0.03). Higher levels of NT-proBNP were found in PE vs. control groups (p < 0.001). sFlt-1/PlGF ratio was higher in E-PE compared to L-PE and GH (p < 0.001). Uric acid levels in PE were significantly higher than in control groups (p < 0.0001). There was a strong positive correlation between UA and Sr in the E-PE serial samples (r = 0.80, p < 0.0001). Lipid peroxidation and lipid peroxidation/TAA ratios were found to be higher in PE, with lower values of TAA. CONCLUSION: The higher levels of Sr and the alterations of redox status found in preeclamptic women, along with the strong correlation between UA and Sr suggest that this element may be involved in the pathogenesis of PE.

Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries.

BACKGROUND: There is little reliable information on human exposure to the metals platinum (Pt), palladium (Pd) and rhodium (Rh), despite their use in enormous quantities in catalytic converters for automobile exhaust systems. OBJECTIVES: To evaluate blood concentrations of Pt (B-Pt), Pd (B-Pd) and Rh (B-Rh) in women from six European and three non-European countries, and to identify potentially influential factors. In addition, molybdenum (Mo) and strontium (Sr) were analysed. METHODS: Blood from 248 women aged 47-61 was analysed by high resolution inductively coupled plasma mass spectrometry under strict quality control. RESULTS: The medians were: B-Pt 0.8 (range <0.6-5.2), B-Pd <5 (<5-9.3), B-Rh <0.4 (<0.4-3.6)ng/L and B-Mo 2.0 (0.2-16) and B-Sr 16.6 (3.5-49) µg/L. Two women with highly elevated B-Pt (242 and 60ng/L), previously cancer treated with cis-platinum, were not included in the data analysis. All elements varied geographically (2-3 times) (B-Pd P=0.05; all other elements P<0.001); variations within each area were generally 5-10 times. Traffic was not associated with increased concentrations. CONCLUSIONS: General population blood concentrations of Pt, Pd and Rh are within or below the single digit ng/L range, much lower than in most previous reports. This is probably due to improved analytical performance, allowing for more reliable information at ultra-trace levels. In general, Mo and Sr agreed with previously reported concentrations. All elements showed geographical and inter-individual variations, but no convincing relationships with self-reported traffic intensity were found. Pt from the antineoplastic drug cis-platinum is retained in the body for years.

Strontium and oxidative stress in normal pregnancy.

BACKGROUND: Pregnancy brings about metabolic and oxidative changes that involve various trace elements and oxidative stress. Strontium (Sr) is a trace element scarcely studied in this context, although it has been suggested that it may play a role in the pathophysiology of preeclampsia. The main aim of this study was to evaluate Sr concentrations and oxidative status in normal pregnancy. METHODS: The study population included non-pregnant women (n=31), healthy pregnant women in the first (n=50), second (n=51) and third (n=53) trimesters of gestation, and women in postpartum period (n=31). Additionally, samples from another twenty pregnant women were obtained in the three trimesters. Strontium, copper, selenium and zinc were measured by inductively coupled plasma-mass spectrometry. Calcium (Ca), uric acid (UA), lipid peroxidation and total antioxidant activity (TAA) were measured by spectrophotometric assays. RESULTS: Strontium remained unchanged until the third trimester of pregnancy, in which significantly higher levels were found (p=0.001). The other elements showed diverse trends during pregnancy. Uric acid levels were significantly different in all groups (p<0.001), increasing gradually as the pregnancy progresses. In serial samples, there was a statistically significant positive correlation between Sr and gestational week of sampling (r=0.31, p=0.01), UA (r=0.40, p=0.001) and lipid peroxidation/TAA ratio (r=0.38, p=0.0002). Additionally, Sr correlated negatively with TAA (r=-0.40, p=0.0001). CONCLUSION: Strontium seems to play a physiological role in the oxidative status of the human organism. Further studies involving Sr and pathologies of pregnancy are warranted.

Serum concentration of several trace metals and physical training.

BACKGROUND: The aim of this study was to observe the concentrations of trace metals boron, lithium, rubidium, antimony, tin and strontium in the serum of athletes from different modalities and sedentary subjects and the possible influence that different energy sports training modalities can have on their concentration. METHODS: Eighty professional athletes and 31 sedentary males participated in the present survey. All of them were living in Cáceres (Spain). Serum boron, lithium, rubidium, antimony, tin and strontium analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The results show higher concentrations in athletes on tin (p < 0.01), rubidium and antimony (p < 0.001) than the control group. In the case of tin, this item had the highest concentrations only in aerobic sports modalities. Regarding rubidium and antimony, the highest concentrations are found in athletes with lower oxygen consumption (aerobic-anaerobic) (p < 0.001), followed by anaerobic group (p < 0.001). CONCLUSION: Our research shows that, probably due to increased water and air intake, especially, trace elements rubidium, antimony and tin reveal major differences in serum concentration of athletes in relation to sedentary subjects. On the other hand, physical training does not change the serum concentration of Boron, Lithium and strontium.

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.

BACKGROUND AND OBJECTIVES: Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003. Calcium metabolism and lumbar bone mineral density were analyzed in these patients. A strontium oral load test was performed: strontium was measured in 240-minute urine and serum 30, 60, and 240 minutes after strontium ingestion; serum strontium concentration-time curve and renal strontium clearance were evaluated to estimate absorption and excretion of divalent cations. RESULTS: Serum strontium concentration-time curve (P<0.001) and strontium clearance (4.9±1.3 versus 3.5±2.7 ml/min; P<0.001) were higher in hypercalciuric stone formers than HNSFs, respectively. The serum strontium-time curve was also higher in hypercalciuric stone formers with low bone mineral density (n=42) than in hypercalciuric stone formers with normal bone mineral density (n=130; P=0.03) and HNSFs with low (n=22; P=0.01) or normal bone mineral density (n=14; P=0.02). Strontium clearance was greater in hypercalciuric stone formers with normal bone mineral density (5.3±3.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.6±2.5 and 3.1±2.5 ml/min, respectively; P=0.03). Multivariate regression analyses displayed that strontium absorption at 30 minutes was positively associated calcium excretion (P=0.03) and negatively associated with lumbar bone mineral density z score (P=0.001) in hypercalciuric stone formers; furthermore, hypercalciuric patients in the highest quartile of strontium absorption had increased stone production risk (odds ratio, 5.06; 95% confidence interval, 1.2 to 20.9; P=0.03). CONCLUSIONS: High calcium absorption in duodenum and jejunum may expose hypercalciuric patients to the risk of stones because of increased postprandial calcium concentrations in urine and tubular fluid. High calcium absorption may identify patients at risk of bone loss among stone formers.

[Determination of strontium content in whole blood and urine by icp-ms].

Parameters of strontium determination in the whole blood and urine of children living near ore deposits containing up to 20% strontium sulfate have been determined. The average strontium content in the whole blood of two children groups of 109.52 ± 11.07 mg/L and 131.62 ± 12.95 mg/L, significantly exceeded the level in the comparison group 44.2 ± 4.24 mg/L. The average strontium contents of two groups of children in urine were 1252.3 ± 332.2 mg/L and 1341.5 ± 241.8 mg/L, these values were 4.2 and 4.5 times higher than in the comparison group 296.4 ± 61.5 mg/L. The conditions for blood and urine sample preparation were optimized to reduce measure errors and to determine strontium at the reference concentration level. The accuracy of the results has been confirmed by analysis of the standard samples Seronorm™ Whole Blood L1, L2, L3 and Seronorm™ Urine.

Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy.

Although a number of studies have measured circulating levels of some trace elements in preeclampsia (PE) and compared to healthy pregnant (HP), there is no consensus yet about the deficiency of some metals and development of hypertensive disorders in pregnancy. The aim of this study was to compare plasmatic levels of Zn, Mn, Co, Cu, Se and Sr among non-pregnant (NP), healthy pregnant (HP), gestational hypertensive (GH) and preeclamptic (PE) women and to correlate these levels with plasma soluble endoglin (sENG) and soluble fms-like tyrosine kinase-1 (sFLT-1), two important antiangiogenic proteins related to PE. A total of 184 women were enrolled in this study (NP=35, GH=51, PE=37 and HP=61). Trace element analyses were carried out with an inductively coupled plasma mass spectrometer (ICPMS). sENG and sFLT-1 plasma concentrations were measured by commercial ELISA kits. The most interesting result is that Sr is higher in PE (63%, P<0.001) compared to HP and their levels are positively correlated with sENG in all three groups of pregnant women. Moreover, we found a negative correlation between Zn and sENG in HP (r=-0.43, P=0.003). Regarding other elements, we found similar levels among pregnant groups. In conclusion, this study showed that Sr may has a role in physiopathology of PE.

Quantification of strontium in human serum by ICP-MS using alternate analyte-free matrix and its application to a pilot bioequivalence study of two strontium ranelate oral formulations in healthy Chinese subjects.

A rapid, sensitive and accurate ICP-MS method using alternate analyte-free matrix for calibration standards preparation and a rapid direct dilution procedure for sample preparation was developed and validated for the quantification of exogenous strontium (Sr) from the drug in human serum. Serum was prepared by direct dilution (1:29, v/v) in an acidic solution consisting of nitric acid (0.1%) and germanium (Ge) added as internal standard (IS), to obtain simple and high-throughput preparation procedure with minimized matrix effect, and good repeatability. ICP-MS analysis was performed using collision cell technology (CCT) mode. Alternate matrix method by using distilled water as an alternate analyte-free matrix for the preparation of calibration standards (CS) was used to avoid the influence of endogenous Sr in serum on the quantification. The method was validated in terms of selectivity, carry-over, matrix effects, lower limit of quantification (LLOQ), linearity, precision and accuracy, and stability. Instrumental linearity was verified in the range of 1.00-500ng/mL, corresponding to a concentration range of 0.0300-15.0µg/mL in 50µL sample of serum matrix and alternate matrix. Intra- and inter-day precision as relative standard deviation (RSD) were less than 8.0% and accuracy as relative error (RE) was within ±3.0%. The method allowed a high sample throughput, and was sensitive and accurate enough for a pilot bioequivalence study in healthy male Chinese subjects following single oral administration of two strontium ranelate formulations containing 2g strontium ranelate.

[Distribution of rubidium, cesium, beryllium, strontium, and barium in blood and urine in general Chinese population].

OBJECTIVE: To investigate the distribution of rubidium (Rb), cesium (Cs), beryllium (Be), strontium (Sr), and barium (Ba) in blood and urine in general Chinese population. METHODS: A total of 18 120 subjects aged 6~60 years were enrolled from 24 regions in 8 provinces in Eastern, Central, and Western China from 2009 to 2010 based on the method of cluster random sampling. Questionnaire survey was conducted to collect the data on living environment and health status. Blood and urine samples were collected from these subjects, and the levels of Rb, Cs, Be, Sr, and Ba in these samples were determined by inductively coupled plasma mass spectrometry. The distribution of these elements in blood and urine in male or female subjects living in different regions was analyzed statistically. RESULTS: In the general Chinese population, the concentration of Be in the whole blood was below the detection limit (0.06 µg/L); the geometric mean (GM) of Ba in the whole blood was below the detection limit (0.45 µg/L), with the 95th percentile (P95)of 1.37 µg/L; the GMs (95% CI)of Rb, Cs, and Sr in the whole blood were 2 374(2 357~2 392) µg/L, 2.01 (1.98~2.05) µg/L, and 23.5 (23.3~23.7) µg/L, respectively; in males and females, the GMs (95%CI)of blood Rb, Cs, and Sr were 2 506 (2 478~2 533) µg/L and 2 248 (2 227~2 270) µg/L, 1.88 (1.83~1.94) µg/L and 2.16 (2.11~2.20) µg/L, and 23.4 (23.1~23.7) µg/L and 23.6 (23.3~23.9) µg/L, respectively(P<0.01, P>0.05, and P>0.05). In the general Chinese population, the GM of urine Be was below the detection limit (0.06 µg/L), while the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 854 (836~873) µg/L, 3.65 (3.56~3.74) µg/L, 39.5 (38.4~40.6) µg/L, and 1.10 (1.07~1.12) µg/L, respectively; in males and females, the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 876 (849~904) µg/L and 832 (807~858) µg/L, 3.83 (3.70~3.96) µg/L and 3.47 (3.35~3.60) µg/L, 42.5 (40.9~44.2) µg/L and 36.6 (35.1~38.0) µg/L, and 1.15 (1.12~1.19) µg/L and 1.04 (1.01~1.07) µg/L, respectively (all P< 0.01). Correlation analyses showed that there were weak correlations between blood Rb and urine Rb (r=0.197)and between blood Sr and urine Sr (r=0.180), but a good correlation between blood Cs and urine Cs (r=0.487). CONCLUSION: The levels of Rb, Cs, Be, Sr, and Ba in the general Chinese population are similar to those reported in other countries, and there is a significant difference in the concentration of each element among the populations living in different regions, as well as significant differences in blood Rb, urine Rb, urine Cs, urine Sr, and urine Ba between males and females.

In vivo measurement of the absorption of strontium in the rumen and small intestine of sheep as an index of calcium absorption capacity.

In the present study, a method was developed for determining the alimentary tract Ca absorption capacity of ruminant animals by measuring the absorption rate of Sr after the administration of an oral dose of strontium chloride acting as a tracer analogue of Ca. A close correlation between the absorption rates of the two tracers was observed upon simultaneous administration of an oral dose of stable Sr and radioactive calcium (r 0·98). The Ca absorption capacity of the rumen and small intestine was determined separately by either directing the solution into the rumen or by diverting it into the post-ruminal tract by vasopressin-induced closure of the ruminoreticular groove. The animals were treated with 1α-hydroxyvitamin D3 administered via subcutaneously implanted mini-osmotic pumps. The effect of elevated plasma 1,25-dihydroxycholecalciferol concentrations on the Ca absorption capacity of the alimentary tract was then determined. An increased rate of Sr absorption was observed in both the rumen and small intestine of sheep after treatment, although it is unclear whether the rumen possesses the same vitamin D-dependent Ca absorption pathway as the small intestine.