Tensile properties and fiber alignment of human supraspinatus tendon in the transverse direction demonstrate inhomogeneity,nonlinearity, and regional isotropy

A recent study (Lake et al., 2009); reported the properties of human supraspinatus tendon (SST) tested along the predominant fiber direction. The SST was found to have a relatively disperse distribution of collagen fibers, which may represent an adaptation to multiaxial loads imposed by the complex loading environment of the rotator cuff. However, the multiaxial mechanical properties of human SST remain unknown. The objective of this study, therefore, was to evaluate the mechanical properties, fiber alignment, change in alignment with applied load, and structure–function relationships of SST in transverse testing. Samples from six SST locations were tested in uniaxial tension with samples oriented transverse to the tendon long-axis. Polarized light imaging was used to quantify collagen fiber alignment and change in alignment under applied load. The mechanical properties of samples taken near the tendon–bone insertion were much greater on the bursal surface compared to the joint surface (e.g., bursal moduli 15–30 times greater than joint; p<0.001). In fact, the transverse moduli values of the bursal samples were very similar to values obtained from samples tested along the tendon long-axis (Lake et al., 2009). This key and unexpected finding suggests planar mechanical isotropy for bursal surface samples near the insertion, which may be due to complex in vivo loading. Organizationally, fiber distributions became less aligned along the tendon long-axis in the toe-region of the stress–strain response. Alignment changes occurred to a slightly lesser degree in the linear-region, suggesting that movement of collagen fibers may play a role in mechanical nonlinearity. Transverse mechanical properties were significantly correlated with fiber alignment (e.g., for linear-region modulus r_s=0.74, p<0.0001), demonstrating strong structure–function relationships. These results greatly enhance current understanding of the properties of human SST and provide clinicians and scientists with vital information in attempting to treat or replace this complex tissue.     

Jumping ability is related to change of direction ability in elite handball players

PurposeThis study investigated the relationship between vertical and horizontal jumping ability and change of direction (COD) to measure athletic performance in 51 elite male handball players.Scope.Countermovement jump (CMJ), peak power, and standing long jump (SLJ) were measured. Participants performed a 20-m sprint test (time measured at 5, 10, and 20 m) and a zigzag test (COD: 135°, 90°, and 45°). The COD deficit, an index of the time required for COD, was calculated. The correlations between CMJ height and zigzag test times were relatively large (at 135°, r =  − 0.607; at 90°, r =  − 0.594; at 45°, r =  − 0.613; p < 0.01), whereas those between CMJ height and COD deficit were moderate (at 135°, r =  − 0.399, p < 0.01; at 90°, r =  − 0.350, p < 0.05; at 45°, r =  − 0.323, p < 0.05). SLJ showed a negative moderate correlation with COD deficit (at 135°, r =  − 0.439, p < 0.01; at 90°, r =  − 0.469, p < 0.01; at 45°, r =  − 0.380, p < 0.01).ConclusionsThis study is the first to analyse SLJ ability and COD deficit parameters of handball players. We found that SLJ ability is moderately related to COD time and deficit; therefore, SLJ measurement may be a useful predictor of athletic performance.     

Vertebral trabecular main direction can be determined from clinical CT datasets using the gradient structure tensor and not the inertia tensor—A case study

Osteoporosis is a wide spread disease with one-third of all women beyond their menopause and a fifth of men above the age of 50 years suffering from it. Patient specific finite element models would be a great improvement for the diagnosis of vertebral fracture risk. Different material models have been proposed, which incorporate information about the anisotropy of trabecular bone in addition to bone mineral density (BMD) using a second rank structure tensor.Two alternative structure measurement methods, gradient structure tensor (GST) and inertia tensor (IT), were investigated. Structure was determined from in situ scans. This was compared to structure computed with the mean intercept length (MIL) tensor from $\mathrm{\mu }\mathrm{CT}$ scans at the same locations.GST delivered information comparable to MIL regarding the structural main direction even at normal dose standard clinical settings (median of the scalar products of up to $\approx 0.98$). IT was not comparable to MIL (median $\approx 0.4$). Neither of the alternatives could determine eigenvalues comparable to these determined from MIL ($p>0.5$).In conclusion, this study could show that the measurement of the structural main direction is possible for in situ scans in a clinical setting. It was shown that the method of choice to determine trabecular main direction in situ is GST. Knowing the main direction a transverse isotropic fabric tensor can be constructed.     

Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes

Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day^?1 doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = ?0.50, p < 0.03) and heart (r = ?0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.     

Quantitative measures of femoral fracture repair in rats derived by micro-computed tomography

Although fracture healing is frequently studied in pre-clinical models of long bone fractures using rodents, there is a dearth of objective quantitative techniques to assess successful healing. Biomechanical testing is possibly the most quantitative and relevant to a successful clinical outcome, but it is a destructive technique providing little insight into the cellular mechanisms associated with healing. The advent of X-ray computed tomography (CT) has provided the opportunity to quantitatively and non-destructively assess bone structure and density, but it is unknown how measurements derived using this technology relate to successful healing. To examine possible relationships, we used a pre-clinical model to test for statistically significant correlations between quantitative characteristics of the callus by micro-CT (μCT) and the bending strength, stiffness, and energy-to-failure of the callus as assessed by three-point bending of excised bones. A closed, transverse fracture was generated in the mid-shaft of rat femurs by impact loading. Shortly thereafter, the rats received a one-time, local injection of either the vehicle or one of four doses of lovastatin. Following sacrifice after 4 weeks of healing, fractured femurs were extracted for μCT analysis and then three-point bending. Setting the region of interest to be 3.2 mm above and below the fracture line, we acquired standard and new μCT-derived measurements. The mineralized callus volume and the mineral density of the callus correlated positively with callus strength (r_xy=?0.315, p=0.016 and r_xy=0.444, p<0.0005, respectively) and stiffness (r_xy=?0.271, p=0.040 and r_xy=0.325, p=0.013, respectively), but the fraction of the callus that mineralized and the moment of inertia of the callus did not. This fraction did correlate with energy-to-failure (r_xy=?0.343, p=0.0085). Of the μCT-derived measurements, quantifying defects within the outer bridging cortices of the callus produced the strongest correlation with both callus strength (r_xy=0.557, p<0.0001) and stiffness (r_xy=0.468, p=0.0002). By both reducing structural defects and increasing mineralization, lovastatin appears to increase the callus strength.     

Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and β cell dysfunction

Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters. We recruited 221 subjects, of whom 130 had MetS by ATP III. We evaluated F, cortisone (E), adipokines, glucose, insulin and lipid profiles as well as urinary (24 h) F, E and THM levels. β Cell function was estimated by the HOMA Calculator. We observed that patients with MetS showed higher levels of THMs, HOMA-IR and leptin and lower levels of adiponectin and HOMA-β but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p < 0.001), waist circumference (r = +0.38, p < 0.01), glycemia (r = +0.37, p < 0.01), and triglycerides (r = +0.18, p = 0.06) and negatively correlated with adiponectin (r = −0.36, p < 0.001), HOMA-β (r = −0.21, p < 0.001) and HDL (r = −0.29, p < 0.01). In a logistic regression model, THM levels were associated with hypertension, hyperglycemia and dyslipidemia. We conclude that MetS is associated with increased urinary THMs but not with F and E levels in plasma or urine. Increased levels of THM, reflecting the daily cortisol production subsequently metabolized, are correlated with hypoadiponectinemia, hypertension, dyslipidemia, insulin resistance and β cell dysfunction. A subtle increased in glucocorticoid production may further account for the phenotypic and biochemical similarities observed in central obesity and Cushing’s syndrome.     

Heterogeneity of yield strain in low-density versus high-density human trabecular bone

Understanding the off-axis behavior of trabecular yield strains may lend unique insight into the etiology of fractures since yield strains provide measures of failure independent of elastic behavior. We sought to address anisotropy of trabecular yield strains while accounting for variations in both density and anatomic site and to determine the mechanisms governing this behavior. Cylindrical specimens were cored from vertebral bodies (n=22, BV/TV=0.11±0.02) and femoral necks (n=28, BV/TV=0.22±0.06) with the principal trabecular orientation either aligned along the cylinder axis (on-axis, n=22) or at an oblique angle of 15° or 45° (off-axis, n=28). Each specimen was scanned with micro-CT, mechanically compressed to failure, and analysed with nonlinear micro-CT-based finite element analysis. Yield strains depended on anatomic site (p=0.03, ANOVA), and the effect of off-axis loading was different for the two sites (p=0.04)—yield strains increased for off-axis loading of the vertebral bone (p=0.04), but were isotropic for the femoral bone (p=0.66). With sites pooled together, yield strains were positively correlated with BV/TV for on-axis loading (R²=58%, p<0.0001), but no such correlation existed for off-axis loading (p=0.79). Analysis of the modulus-BV/TV and strength-BV/TV relationships indicated that, for the femoral bone, the reduction in strength associated with off-axis loading was greater than that for modulus, while the opposite trend occurred for the vertebral bone. The micro-FE analyses indicated that these trends were due to different failure mechanisms for the two types of bone and the different loading modes. Taken together, these results provide unique insight into the failure behavior of human trabecular bone and highlight the need for a multiaxial failure criterion that accounts for anatomic site and bone volume fraction.     

Can self-report instruments of shoulder function capture functional differences in older adults with and without a rotator cuff tear?

Rotator cuff tears (RCT) are prevalent in older individuals and may compound age-associated functional declines. Our purpose was to determine whether self-report measures of perceived functional ability are valid for older patients with RCT. Twenty five subjects participated (12M/13F; age = 63.9 ± 3.0 years); 13 with RCT and 12 controls (CON). Participants completed self-report measures of shoulder function (SST, ASES, WORC) and health-related quality of life (SF-36). Isometric joint moment and range of motion (ROM) were measured at the shoulder. Relationships among functional self-reports, and between these measures and joint moment and ROM were assessed; group differences for total and subcategory scores were evaluated. There were significant correlations among self-reports (r_s = 0.62–0.71, p ⩽ 0.02). For RCT subjects, ASES was associated with all joint moments except adduction (p ⩽ 0.02); SST, ASES, and WORC were associated with abduction and external rotation ROM (p ⩽ 0.04). For RCT subjects, SST and WORC were associated with SF-36 physical function subcategory scores (p ⩽ 0.05). The RCT group scored worse than CON on all functional self-reports (p < 0.01) and WORC and ASES subcategories (p < 0.01). In conclusion, SST, ASES, and WORC demonstrate utility and discriminant validity for older individuals by distinguishing those with RCT, but this work suggests prioritizing ASES given its stronger association with functional group strength.     

On the interrelationship of permeability and structural parameters of vertebral trabecular bone: a parametric computational study

To characterise the flow of a fluid through a uniform porous medium, the medium may be completely described by its permeability, a measure of flow resistance. Fluid flow in the intertrabecular spaces of cancellous bone has been recognised as an important factor in a number of physical phenomena. In order to investigate the interdependence of permeability, porosity and the structural parameters, we adapted a morphological model and systematically varied its structural parameters. By simulating a viscous Stokes flow regime, we were able to estimate the anisotropic permeability tensor and performed an extensive, stepwise multivariate regression analysis to establish empirical relationships between the morphological parameters and the permeability for the anatomical directions individually. The regression analysis indicated high values of determination coefficients [0.88 < R² < 0.89 (transversal directions) and R² = 0.60 (longitudinal direction), porosity-based prediction and R² = 0.98 for all directions and information presented to the regression model]. We conclude that a pooled set of structural parameters may explain up to 98% of the permeability variability, the regression model predicts permeability values that match experimental data, and a good prediction performance could be achieved by only incorporating the porosity and either the degree of anisotropy (0.89 < R² < 0.91) or the trabecular spacing predictor (0.96 < R² < 0.97). These conclusions imply that trabecular thickness and shape parameters only play a minor role in the determination of vertebral trabecular bone permeability. However, a major limitation of the model is that it reflects an idealisation of the real, regionally varying structure of trabecular bone. Therefore, the goodness-of-fit estimates we are presenting should be considered as an upper bound limitation regarding the prediction performance.     

Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone – An experimental and finite element study

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n = 11, male, age 18–78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (E_eq) increased with increasing crystallinity (r = 0.730, p = .011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r = 0.718, p = .019). In addition, the normalized shear modulus g₁ (r = −0.780, p = .005) decreased with increasing collagen ratio (amide III/CH₂) at the tissue-level, but increased (r = 0.696, p = .025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only E_eq, g₂ and relaxation time τ₁ from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p < .01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone.     

The relationship between fetal and maternal selenium concentrations in sheep and goats

In this study, biological samples (slaughterhouse material) were collected from 30 sheep and 36 goats and classified according to gestational stage into either early or late gestation. Samples consisted of allantoic fluid, amniotic fluid, fetal liver, fetal kidney, fetal thyroid gland, maternal plasma and liver to determine selenium (Se) concentrations throughout gestation. The Se concentrations in the allantoic fluid, fetal liver and kidney increased significantly (p < 0.01) during late gestation. Concurrently, the Se concentrations in amniotic fluid, maternal plasma and liver decreased significantly (p < 0.01) over time. Significant (p < 0.01) positive relationships were recorded between the age of the fetus and Se concentrations in the allantoic fluid (r = 0.57–0.75), fetal liver (r = 0.43–0.59) and kidney (r = 0.80–0.81) in both sheep and goats. A significant (p < 0.05) positive relationships were also recorded between the Se concentrations in the allantoic fluid and fetal liver (r = 0.35–0.37), the maternal plasma and liver Se concentrations (r = 0.37–0.57) between sheep and goats. A significant (p < 0.05) negative correlation was recorded between the Se concentrations in the allantoic fluid with maternal plasma of sheep (r = −0.41) as well as between the fetal liver and maternal liver Se (r = −0.22 to 0.50) and a negative correlation (r = −0.42 to 0.43) (p < 0.01) between Se concentrations in the fetal liver and amniotic fluid in both sheep and goats, respectively. Se concentration in the fetal liver was significantly (p < 0.01) higher than that of the kidney and thyroid. In the thyroid gland no morphological differences were noted. Strong fetal–maternal relationships in Se concentration were evident throughout the gestational period and dams seem to sacrifice Se levels in order to maintain that in the fetus. Se concentrations in the amniotic and allantoic fluids could be used as a possible indicator of the Se status of the fetus throughout gestation.     

Correlations of selenium and selenoprotein P with asymmetric dimethylarginine and lipid profile in patients with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular diseases (CVD). Accumulating evidence has suggested that selenium (Se) is of importance for optimal function of the cardiovascular system. This study aimed to investigate the associations of selenium and selenoprotein P (SePP) with asymmetric dimethylarginine (ADMA) and lipid profile in women with PCOS.MethodsIn this cross-sectional study, 125 females aged 18–45 years diagnosed with PCOS were recruited. An interviewer-administered questionnaire was applied to gather the relevant demographic characteristics, detailed clinical information, and lifestyle habits of participants. Fasting blood samples were obtained to measure biochemical parameters. Serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), ADMA, and lipid profiles as well as anthropometric measurements were assessed across tertiles of serum Se and SePP concentrations.ResultsThere was a positive correlation between serum Se and SePP concentrations (r = 0.434, p < 0.001). Serum Se level was inversely correlated with ADMA (r = −0.21, p = 0.025) and TG (r = −0.17, p = 0.041) concentrations. There were also inverse correlations between SePP and ADMA (r = −0.34, p < 0.001), TG (r = −0.21, p = 0.019), and oxidized low density lipoprotein (ox-LDL) (r = −0.25, p = 0.007) levels. No significant relationship was found between serum Se and SePP concentrations with total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B100), total testosterone, SHBG, and free androgen index as well as anthropometric parameters (All p > 0.05).ConclusionThe present study found that Se and SePP levels were inversely correlated with ADMA and TG concentrations as well as ox-LDL levels.     

Assessing reproductive biology of Macrobrachium lamarrei in the Ganges River (NW Bangladesh) in relation to environmental parameters

Macrobrachium lamarrei (H. Milne-Edwards, 1837) is a well-known freshwater prawn species of Bangladesh. The aim of the research is to explore various reproductive aspects (size at sexual maturity, reproductive period and fecundity) of M. lamarrei in the Ganges River, Bangladesh through October 2012 to September 2013. We also study the environmental parameters and their impact on reproduction of M. lamarrei. A total 391 (ovigerous = 141, non-ovigerous = 250) female specimens were collected using Drag net. The TL₅₀ (the TL at which 50% of individuals become mature) was calculated by a logistic equation as 5.20 cm. Based on the availability of ovigerous females the spawning season was February-November with the peak June-July. Further, 50% and 90% ovigerous females were observed when Fulton’s condition factor (K_F) was 0.85 and 1.03, respectively. The total fecundity (F_T) was ranged from 65 to 370 where TL was 4.20–6.40 cm and BW was 0.84–2.50 g. Fecundity was found to be highly correlated with TL (r² ≥ 0.96, r_s = 0.96, p < 0.0001) and BW (r² ≥ 0.88, r_s = 0.93, p < 0.0001). Temperature (r_p = 0.82, p = 0.009), dissolved oxygen (DO) (r_p = −0.83, p = 0.0007), pH (r_p = 0.80, p = 0.0014) and total alkalinity (r_p = −0.87, p = 0.0002), were highly correlated with ovigerous females. The average temperature on peak spawning season was 32 °C. Also, the spawning period connected with the peak rainfall and showed a notable relation between rainfall and ovigerous females. In addition, exploration of long data series pointed that yearly average air temperature is rising by 0.029 °C yr⁻¹, whereas yearly average rainfall is falling by 2.96 mm yr⁻¹. Therefore, the result will be helpful for the sustainable management and conservation of M. lamarrei through fixed permissible mesh size and establishment of a ban period in the Ganges River, Bangladesh and adjoining ecosystems.     

Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6–31.0 kg/m²). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = ?0.31; p < 0.05). In addition, fasting (r = ?0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = ?0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.     

Does adiposity affect muscle function during walking in children?

The biomechanical mechanisms responsible for the altered gait in obese children are not well understood, particularly as they relate to increases in adipose tissue. The purpose of this study was to test the hypotheses that as body-fat percentage (BF%) increased: (1) knee flexion during stance would decrease while pelvic obliquity would increase; (2) peak muscle forces normalized to lean-weight would increase for gluteus medius, gastrocnemius, and soleus, but decrease for the vasti; and (3) the individual muscle contributions to center of mass (COM) acceleration in the direction of their primary function(s) would not change for gluteus medius, gastrocnemius, and soleus, but decrease for the vasti. We scaled a musculoskeletal model to the anthropometrics of each participant (n=14, 8–12 years old, BF%: 16–41%) and estimated individual muscle forces and their contributions to COM acceleration. BF% was correlated with average knee flexion angle during stance (r=−0.54, p=0.024) and pelvic obliquity range of motion (r=0.78, p<0.001), as well as with relative vasti (r=−0.60, p=0.023), gluteus medius (r=0.65, p=0.012) and soleus (r=0.59, p=0.026) force production. Contributions to COM acceleration from the vasti were negatively correlated to BF% (vertical— r=−0.75, p=0.002, posterior— r=−0.68, p=0.008), but there were no correlation between BF% and COM accelerations produced by the gastrocnemius, soleus and gluteus medius. Therefore, we accept our first, partially accept our second, and accept our third hypotheses. The functional demands and relative force requirements of the hip abductors during walking in pediatric obesity may contribute to altered gait kinematics.     

Effect of different iodide intake during pregnancy and lactation on thyroid and cardiovascular function in maternal and offspring rats

ObjectiveWe aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats.MethodsPregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system.ResultsHigh iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = −0.909, p = 0.012; r = −0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = −0.917, p = 0.01; r = −0.859, p = 0.028; r = −0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = −0.990, p = 0.0002) and Txnrd2 expression (r = −0.979, p = 0.001; r = −0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased.ConclusionIn addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.     

Oxidative stress,redox signaling pathways,and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer

Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.     

Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population

Leptin, the obesity gene protein product, is a hormone with multiple physiological functions in the human. However, there are few reports in the literature on its role in trace element metabolism in the normal population. Therefore, we investigated the association among serum leptin, zinc, copper, and zinc/copper ratio in 570 healthy men and women aged 15 yr and older. Serum leptin assay was done with a commercial enzymelinked immunosorbent assay kit; serum zinc and copper levels were measured by an atomic absorption spectrophotometer. Serum leptin was found to be positively associated with age (r=0.254, p<0.001), sex (r=0.406, p<0.001), body mass index (BMI) (r=0.553, p<0.001), and serum copper (r=0.419, p<0.001), but negatively associated with the zinc/copper ratio (r=−0.423, p<0.001). There was no significant association between serum leptin and zinc (r=−0.131, p>0.05). When the confounding effects of age, sex, and BMI were removed, serum leptin was still positively associated with serum copper (r=0.197, p=0.02) and the serum zinc/copper ratio (r=−0.182, p=0.03). These results suggest that copper and not zinc has an effect on serum leptin levels.     

Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans?

Fish species may contain considerable amounts of trace elements, such as selenium (Se), arsenic (As), and mercury (Hg). The present study investigated the relationships between dietary intake of these elements and cutaneous bleeding time and blood lipids in 32 healthy volunteers. For 6 wk, one group (n=11) consumed approx 250 g Se-rich fish daily, providing them with an average Se intake of 115±31 μg Se/d, Hg intake of 18±8 μg/d, and As intake of 806±405 μg/d, all values analyzed in 4-d duplicate food collections. To study the effect of Se alone, one group (n=11) included Se-rich bread in their normal diet, giving them a Se intake (135±25 μg/d) that was comparable to the fish group. A control group (n=10) ate their normal diet, providing 77±25 gmg Se/d, 3.1±2.5 μg Hg/d, and 101±33 μg As/d. The dietary As load strongly correlated both with bleeding times and changes in bleeding times (r=0.48,p<0.01 andr=0.54,p<0.002, respectively). Dietary Hg showed a positive correlation with LDL-cholesterol (r=0.55,p<0.01), whereas dietary Hg in the fish group showed a strong negative relationship with HDL-cholesterol (r=?0.76,p<0.01). Selenium seemed to have only a modest effect on bleeding time. Our results suggest that mercury and arsenic from fish may be factors contributing to or modifying some of the known effects of fish ingestion.     

Variations in the GST activity are associated with single and combinations of GST genotypes in both male and female diabetic patients

In the present cross sectional study, we aimed to ascertain the relative associations of GST genotypes with GST activity variations and also with the risk to DMT2 predisposition among men and women separately. Clinical samples obtained from 244 DMT2 cases (120 Males and 124 Females) and 228 controls (117 Males and 111 Females) belonging to Asian Indian ethnicity were used to test for glycemic index, lipid profile, GST activity and GST genotypes. The frequencies of single and combinations of GST genotypes were statistically examined for their association with DMT2 risk among both study groups. The GST activity is significantly lowered in DMT2 group compared to controls (p = < 0.001). This reduction is found to be subjective to single and combinations of GST genotypes among diabetic patients. The frequency distribution for single, double and triple combinations of genotypes of GSTT1, GSTM1 and GSTP1 showed the varying degrees of association with DMT2 risk from 0.5 to 5.6-fold among male and female patients (for all associations, p value was <0.05). Interestingly, GST activity was lowered in both male and female patients with single or combinational genotypes of GSTM1 (Null), GSTT1 (Null), and P1 (V/V) (for all associations, p value was = <0.0001). The reduced anti-oxidant capacity among diabetic patients with certain GST genotypes may have some important implications for disease diagnosis and therapy.