Estrogen attenuates HSP 72 expression in acutely exercised male rodents

Estrogen has been shown to reduce post-exercise skeletal muscle damage. Exercise-induced muscle damage may be a factor in the elevated post-exercise expression of heat-shock proteins (HSPs). Thus, the present investigation was conducted in order to examine the influence of estrogen on post-exercise levels of HSP 72 and heat-shock cognate, HSC 73, in male and female rodents. Prior to an acute bout of treadmill running, male and female Sprague-Dawley rats received daily injections of either 40 microg x kg(-1) of beta-estradiol 3-benzoate or olive oil vehicle for 2 weeks. A two- to fourfold reduction in post-exercise HSP 72 content was observed in the heart, liver, lung and red and white vastus muscles of estradiol-treated males compared with their vehicle-injected counterparts (P < 0.05). Compared to the males, the females had significantly lower post-exercise HSP 72 levels which were not affected by estradiol supplementation. Moreover, estradiol administration in male rodents resulted in a HSP response similar to that of females following exercise. Thus, the results of the present investigation suggest that estrogen is the factor responsible for the observed differences in post-exercise HSP 72 levels between males and females.     

The influence of exogenous carbohydrate provision and pre-exercise alkalosis on the heat shock protein response to prolonged interval cycling

The aim of this study was to observe the intracellular heat shock protein 72 (HSP72) and heme oxygenase-1 (HSP32) response to prolonged interval cycling following the ingestion of carbohydrates (CHO) and sodium bicarbonate (NaHCO₃). Six recreationally active males (mean ± SD; age 23.2 ± 2.9 years, height 179.5 ± 5.5 cm, body mass 76.5 ± 6.8 kg, and peak power output 315 ± 36 W) volunteered to complete a 90 min interval cycling exercise on four occasions. The trials were completed in a random and blinded manner following ingestion of either: placebo and an artificial sweetener (P–P), NaHCO₃ and sweetener (B–P), placebo and CHO (P–CHO), and NaHCO₃ and CHO (B–CHO). Both HSP72 and HSP32 were significantly increased in monocytes and lymphocytes from 45 min post-exercise (p ≤ 0.039), with strong relationships between both cell types (HSP72, r = 0.83; HSP32, r = 0.89). Exogenous CHO had no influence on either HSP72 or HSP32, but the ingestion of NaHCO₃ significantly attenuated HSP32 in monocytes and lymphocytes (p ≤ 0.042). In conclusion, the intracellular stress protein response to 90 min interval exercise is closely related in monocytes and lymphocytes, and HSP32 appears to be attenuated with a pre-exercise alkalosis.     

Myocardial Na+/H+ exchanger-1 (NHE1) content is decreased by exercise training

The effect of exercise training on myocardial Na⁺/H⁺ exchanger-1 (NHE1) protein expression was examined. Adult female Sprague–Dawley rats were randomly divided into sedentary (S; n?=?8) and exercised (E; n?=?9) groups. Twenty-four hours after the last exercise bout, hearts were weighed and connected to an isolated perfused working heart apparatus for evaluation of cardiac functional performance. Heart weight and heart weight/body weight from E rats was significantly increased by 7.1 and 7.2 % (P?<?0.05), respectively, compared with S hearts. The E hearts displayed 15 % greater cardiac output and 35 % external cardiac work compared with the S group at both low and high workloads (P?<?0.05 for both parameters). Left ventricular tissue from the same hearts was homogenized and NHE1 and Na⁺/Ca²⁺ exchanger (NCX) content determined by Western blotting. E hearts had a 38 % (P?<?0.001) reduction in NHE1 content related to S hearts, and there was no difference in NCX content between groups. Cytochrome c oxidase activity in plantaris increased by 100 % (P?<?0.05) and was assessed as a marker of mitochondria content and to verify training status. Our data indicate that exercise training at an intensity that results in cardiac hypertrophy and improved performance is accompanied by decreased NHE1 content in heart.     

Serum levels of HSP70 and other DAMP proteins can aid in patient diagnosis after traumatic injury

Danger-associated molecular patterns (DAMPs) are activated by endogenous signals that originate from stressed, injured, or necrotic cells, signifying “danger” to the host. In this study, we evaluated the expression of the DAMP heat shock protein 70 (HSP70) in trauma patients with and without secondary infections. Levels of glucose (GLU), procalcitonin (PCT), total cholesterol (T-Chol), and white blood cell (WBC) counts were also evaluated at three time stages after trauma. Our analysis showed that the levels of serum HSP70 in patients with minor, moderate, and severe injuries were significantly higher than in healthy patients at each time point post-injury (P?<?0.01), and levels of serum HSP70 in the severe injury group were significantly higher than in the minor injury group at 1–6 h after trauma (P?=?0.047). HSP70 was correlated with GLU and was negatively correlated with T-Chol in the period 1–6 h after injury (P?=?0.008/0.032). WBC and GLU were elevated after trauma, with mutual positive correlation (P?<?0.001). PCT levels increased later than WBC counts and GLU levels; these levels were correlated at the two later time periods, 24–48 h and 60–90 h (P?=?0.008/0.041). PCT continued to rise in patients with secondary infection, but PCT dropped at the third time period in patients without secondary infection. In summary, our results suggest that danger and stress theory can be used to predict severity of trauma.     

Effects of Iron Glycine Chelate on Growth, Tissue Mineral Concentrations, Fecal Mineral Excretion, and Liver Antioxidant Enzyme Activities in Broilers

The study was conducted to determine the effects of iron glycine chelate (Fe-Gly) on growth, tissue mineral concentrations, fecal mineral excretion, and liver antioxidant enzyme activities in broilers. A total of 360 1-day-old commercial broilers (Ross?×?Ross) were randomly allotted to six dietary treatments with six replications of ten chicks per replicate. Broilers were fed a control diet with no Fe supplementation, while five other treatments consisted of 40, 80, 120, and 160?mg Fe/kg diets from Fe-Gly, and 160?mg Fe/kg from ferrous sulfate, respectively. After a 42-day feeding trial, the results showed that 120 and 160?mg Fe/kg as Fe-Gly improved the average daily gain (P?<?0.05) and average daily feed intake (P?<?0.05) of broilers (4?C6?weeks). Addition with 120 and 160?mg Fe/kg from Fe-Gly and 160?mg Fe/kg from FeSO₄ increased Fe concentration in serum (P?<?0.05), liver (P?<?0.05), breast muscle (P?<?0.05), tibia (P?<?0.05), and feces (P?<?0.01) at 21 and 42?days. There were linear responses to the addition of Fe-Gly from 0 to 160?mg/kg Fe on Fe concentration in serum (21?days, P?=?0.005; 42?days, P?=?0.001), liver (P?=?0.001), breast muscle (P?=?0.001), tibia (P?=?0.001), and feces (21?days, P?=?0.011; 42?days, P?=?0.032). Liver Cu/Zn superoxide dismutase activities of chicks were increased by the addition of 80, 120, and 160?mg Fe/kg as Fe-Gly to diets at 42?days. There were no differences in liver catalase activities of chicks among the treatments (P?>?0.05). This study indicates that addition with Fe-Gly could improve growth performance and iron tissue storage and improves the antioxidant status of broiler chickens.     

Plasma metabolic profile in COPD patients: effects of exercise and endurance training

The study examines plasma metabolic profiles of patients with chronic obstructive pulmonary disease (COPD) to prove whether the disease influences metabolism at rest and after endurance training. This is based on the hypothesis that metabolome levels should reflect impaired skeletal muscle bioenergetics in COPD. The study aims to test this hypothesis by evaluating plasma metabolic profiles in COPD patients before and after 8?weeks of endurance exercise training. We studied blood samples from 18 COPD patients and 12 healthy subjects. Pre- and post-training blood plasma samples at rest and after constant-work rate exercise (CWRE) at 70% of pre-training Watts peak were analyzed by ¹H-nuclear magnetic resonance spectroscopy to assess metabolite profiles. The two groups presented training-induced physiological changes in the VO₂ peak and in blood lactate levels (P?<?0.01 each). Before training, the two groups also showed differences in metabolic profiles at rest (P?<?0.05). Levels of valine (r?=?0.51, P?<?0.01), alanine (r?=?0.45, P?<?0.05) and isoleucine (r?=?0.51, P?<?0.01) were positively associated with body composition (Fat Free Mass Index). While training showed a significant impact on the metabolic profile in healthy subjects (P?<?0.001), with changes in levels of amino acids, creatine, succinate, pyruvate, glucose and lactate (P?<?0.05 each), no equivalent training-induced effects were seen in COPD patients in whom only lactate decreased (P?<?0.05). This study shows that plasma metabolic profiling contributes to the phenotypic characterization of COPD patients.     

Evaluation of Selenium,Redox Status and Their Association with Plasma Amyloid/Tau in Alzheimer’s Disease

The aim of the study was to evaluate blood selenium and antioxidants as possible oxidative stress markers in Alzheimer’s disease (AD) along with amyloid β42 (Aβ42) and tau by comparing them with vascular dementia (VD) and age-matched healthy controls. Selenium, total tau, Aβ42, glutathione (GSH) and malondialdehyde (MDA) levels and the activities of antioxidant enzymes were analysed in the blood of AD patients (n?=?30), VD patients (n?=?35) and controls (n?=?40) from South India. Plasma Aβ42 level was significantly higher (P?<?0.001) in both AD and VD compared to controls. Total tau and tau-to-amyloid ratio were significantly lower in both AD and VD (P?<?0.001), compared to controls, and a significant difference (P?<?0.01 and P?<?0.05, respectively) was also observed between AD and VD. The receiver operating characteristic (ROC) curve-derived cutoff values of <3.5 for tau-to-Aβ42 ratio and <520 pg/ml for total tau showed sensitivity and specificity of around 67–72 % for differentiating AD from VD and around 90 % for AD from controls, indicating that they could serve as reliable AD-specific markers. The MDA levels were significantly higher (P?<?0.001) in both dementia groups along with a significant decrease (P?<?0.001) in reduced GSH levels, indicating elevated oxidative stress and altered redox status in both forms of dementia. Selenium levels did not vary significantly between the three groups. The activity of glutathione peroxidase increased in both AD and VD compared to controls, with a concomitant decrease in glutathione reductase and glucose-6-phospate dehydrogenase (P?<?0.001) activity. The activity of thioredoxin reductase was significantly lower in both patient groups (P?<?0.001) compared to healthy controls. No correlation was observed between selenium and activities of selenoenzymes, tau, Aβ42 or tau-to-Aβ42 ratio, when analysing independently, indicating that blood selenium may not be directly involved in Aβ production and in regulating tau/Aβ42-mediated mechanism in AD. The present study emphasizes the enhanced oxidative stress in AD pathology and plasma tau and tau-to-amyloid ratio as possible markers to differentiate AD from VD. The study also points that blood selenium may not be involved in regulating oxidative stress in AD, and a longitudinal study correlating plasma and cerebrospinal fluid (CSF) selenium and selenoprotein levels is warranted.     

Combined Impact of Exercise and Temperature in Learning and Memory Performance of Fluoride Toxicated Rats

In previous studies, we investigated a link between high fluoride exposure and functional IQ deficits in rats. This study is an extension conducted to explore the combined influence of physical exercise and temperature stress on the learning ability and memory in rats and to assess whether any positive modulation could be attenuated due to exercise regimen subjected to F-toxicated animals at different temperatures. Accumulation of ingested fluoride resulted significant inhibition in acetylcholinesterase activity (P?<?0.05), plasma cortisol levels (P?<?0.05), and impaired the acquisition, performance, latency time, and retention in fluoride-exposed animals. Fluoride-toxicated rats took more number of sessions during the learning phase [F _{5, 35}?=?19.065; P?<?0.05] and post hoc analysis on the number of correct choices revealed that there was a significant effect of treatments [F _{5, 30}?=?15.763; P?<?0.05]; sessions [F _{8, 240}?=?58.698; P?<?0.05]; and also significant difference in the interactions [F _{40, 240}?=?1.583; P?<?0.05]. The latency data also revealed a significant difference between groups [F _{5, 30}?=?28.085; P?<?0.05]; time?=?[F _{8, 240}?=?136.314; P?<?0.05]; and there was a significant difference in the interactions [F _{40, 240}?=?2.090; P?<?0.05]. In order to ascertain if interdependence between fluoride concentrations and the foregoing free radical parameters, respective correlation coefficients were calculated and results clearly emphasize the positive role of exercise in the promotion of cognitive functions by decreasing fluoride levels in rat hippocampus. A significant recovery in cognitive function was noticed in all the exercised animals due to reduced burden of brain oxidative stress. In comparison to exercise regimens performed at different temperatures, high (35?°C) and low temperatures (20?°C) led to a slower acquisition and poor retention of the task when compared to thermo neutral temperatures (25 and 30?°C). Thus exercise up-regulate antioxidant defenses and promote learning abilities in fluorotic population.     

Role of alpha- and beta-adrenoreceptors in rat monocyte/macrophage function at rest and acute exercise

Previous studies from our laboratory have demonstrated that a single bout of moderate exercise stimulates macrophage function, increasing phagocytic capacity, and production of hydrogen peroxide and nitric oxide (NO˙) through nuclear factor kappa B activation. In this work, we investigated the role of α- and β-adrenoreceptors on the function of monocyte/macrophages during rest and exercise. Adult male Wistar rats were i.p. administered (100 μL/100 g) with specific adrenergic antagonists before an acute moderate exercise bout: prazosin (α₁-specific antagonist 2 mg/kg), propranolol (unspecific β_1/β₂ antagonist 10 mg/kg), double blockade (α₁ and β_1/β₂), or phosphate-buffered saline (control). Acute exercise consisted in a single swimming session of moderate intensity (5 % body weight overload on the chest) for 60 min. Control groups (rest) received the same antagonists and were killed 60 min after drug administration. Exercise increased phagocytic capacity (1.7-fold, p?<?0.05), NO˙ production (5.24 fold, p?<?0.001), and inducible nitric oxide synthase (NOS2) expression (by 58.1 %), thus suggesting macrophage activation. The β-adrenoreceptor blockade did not change this behavior. In resting animals, α₁ antagonist, as well as the double (α₁/β) blockade, however, further increased phagocytic capacity (by up to 261 %, p?<?0.001), NO˙ production (by up to 328 %, p?<?0.001), and the expressions of NOS2 (by 182 %, p?<?0.001) and HSP70 (by 42.5 %, p?<?0.01) suggesting a tonic inhibitory effect of α₁ stimulation on macrophage activation. In exercised animals, α₁-blockade showed similar enhancing effect on phagocytic indices and expressions of NOS and HSP70, particularly in double-blocked groups, although NO˙ production was found to be reduced in exercised animals submitted to both α- and β-blockade. Redox (glutathione) status and lipoperoxidation were evaluated in all test groups and approximately paralleled macrophage NO˙ production. We suggest the prevalence of a peripheral α₁-adrenoreceptor inhibitory tonus that limits macrophage responsiveness but operates differently after physical exercise.     

Effects of negative air ions on oxygen uptake kinetics,recovery and performance in exercise: a randomized,double-blinded study

Limited research has suggested that acute exposure to negatively charged ions may enhance cardio-respiratory function, aerobic metabolism and recovery following exercise. To test the physiological effects of negatively charged air ions, 14 trained males (age: 32?±?7 years; \( \overset{\cdotp }{V}{\mathrm{O}}_{2 \max } \) : 57?±?7 mL min^?1 kg^?1) were exposed for 20 min to either a high-concentration of air ions (ION: 220?±?30?×?10³ ions cm^?3) or normal room conditions (PLA: 0.1?±?0.06?×?10³ ions cm^?3) in an ionization chamber in a double-blinded, randomized order, prior to performing: (1) a bout of severe-intensity cycling exercise for determining the time constant of the phase II \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) response (τ) and the magnitude of the \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) slow component (SC); and (2) a 30-s Wingate test that was preceded by three 30-s Wingate tests to measure plasma [adrenaline] (ADR), [nor-adrenaline] (N-ADR) and blood [lactate] (B_Lac) over 20 min during recovery in the ionization chamber. There was no difference between ION and PLA for the phase II \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) τ (32?±?14 s vs. 32?±?14 s; P?=?0.7) or \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) SC (404?±?214 mL vs 482?±?217 mL; P?=?0.17). No differences between ION and PLA were observed at any time-point for ADR, N-ADR and B_Lac as well as on peak and mean power output during the Wingate tests (all P?>?0.05). A high-concentration of negatively charged air ions had no effect on aerobic metabolism during severe-intensity exercise or on performance or the recovery of the adrenergic and metabolic responses after repeated-sprint exercise in trained athletes.     

Genetic diversity of Cypripedium calceolus in Poland

In this work we assessed the genetic diversity of 32 C.?calceolus populations from Poland. Mean genetic diversity was moderate (P?=?36.4%, A?=?1.58, H _O?=?0.143, F _IS?=?0.059), and seven geographic regions did not differ significantly in their levels of polymorphism (p?>?0.05), although allele frequencies varied greatly. Only four unique alleles were found, at three sites in southern and southeastern Poland. Genetic (P, A) and genotypic diversity parameters (G, G _U) were significantly correlated with population size (p?<?0.001). In the 32 studied populations we separated 422 different multilocus genotypes; none was common to all populations. Overall population differentiation was moderate at 0.137 (p?<?0.001), but we found a significant pattern of isolation by distance for the whole dataset (r ²?=?0.65, p?<?0.001). Our chloroplast DNA (cpDNA) results suggest a single evolutionary lineage and a common origin for all Polish C.?calceolus populations. Information about the genetic health of C.?calceolus populations should be useful in developing conservation strategies.     

Hair Iron and Other Minerals’ Level in Breast Cancer Patients

Little is known about hair minerals in cancer patients, and serum iron level has been shown to be elevated in breast cancer patients. Therefore, the aim of this study was to evaluate hair iron and hair minerals’ level related to hair iron in breast cancer patients compared to controls. We compared hair mineral analysis data of 40 breast cancer subjects with age and body mass index-matched normal control data (n?=?144) by cross-sectional analysis. All breast cancer patients were newly diagnosed at one Breast Cancer Center in Ajou University and had their hair cut before anti-cancer chemotherapy, and the normal controls (without breast cancer) also had their hair cut for various reasons in out-patient clinics of the Department of Family Practice and Community Health. Breast cancer patients had low calcium, magnesium, iron, copper, manganese, and zinc, whereas they had high arsenic, sodium, and potassium compared with the normal control. The hair iron level was positively correlated with hair calcium (r?=?0.761, P?<?0.001), magnesium (r?=?0.643, P?<?0.001), and manganese (r?=?0.550, P?<?0.001) and negatively correlated with arsenic (r?=??0.537, P?<?0.001). The hair iron level was significantly associated with the hair calcium (β?=?0.778, P?<?0.001) and manganese (β?=?0.240, P?<?0.001) by using multiple linear regression analysis. We observed different hair mineral patterns in breast cancer patients compared to normal controls. Especially, hair iron level was significantly reduced and associated with hair calcium and manganese levels.     

The Influences of Chromium Supplementation on Glycemic Control,Markers of Cardio-Metabolic Risk,and Oxidative Stress in Infertile Polycystic ovary Syndrome Women Candidate for In vitro Fertilization: a Randomized,Double-Blind,Placebo-Controlled Trial

This study was carried out to investigate the effects of chromium intake on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome (PCOS) women candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was done among 40 subjects with infertile PCOS candidate for IVF, aged 18–40 years old. Individuals were randomly allocated into two groups to take either 200 μg/day of chromium (n?=?20) or placebo (n?=?20) for 8 weeks. Biochemical parameters were assessed at baseline and at end-of-trial. Compared with the placebo, taking chromium supplements led to significant reductions in fasting plasma glucose (??2.3?±?5.7 vs. +?0.9?±?3.1 mg/dL, P?=?0.03), insulin levels (??1.4?±?2.1 vs. +?0.4?±?1.7 μIU/mL, P?=?0.004), homeostatic model of assessment for insulin resistance (??0.3?±?0.5 vs. +?0.1?±?0.4, P?=?0.005), and a significant increase in quantitative insulin sensitivity check index (+?0.004?±?0.008 vs. ??0.001?±?0.008, P?=?0.03). In addition, chromium supplementation significantly decreased serum triglycerides (??19.2?±?33.8 vs. +?8.3?±?21.7 mg/dL, P?=?0.004), VLDL- (??3.8?±?6.8 vs. +?1.7?±?4.3 mg/dL, P?=?0.004) and total cholesterol concentrations (??15.3?±?26.2 vs. ??0.6?±?15.9 mg/dL, P?=?0.03) compared with the placebo. Additionally, taking chromium supplements was associated with a significant increase in plasma total antioxidant capacity (+?153.9?±?46.1 vs. ??7.8?±?43.9 mmol/L, P?<?0.001) and a significant reduction in malondialdehyde values (?0.3?±?0.3 vs. +?0.1?±?0.2 μmol/L, P?=?0.001) compared with the placebo. Overall, our study supported that chromium administration for 8 weeks to infertile PCOS women candidate for IVF had beneficial impacts on glycemic control, few variables of cardio-metabolic risk, and oxidative stress.     

The Effect of Manganese-induced Cytotoxicity on mRNA Expressions of HSP27, HSP40, HSP60, HSP70 and HSP90 in Chicken Spleen Lymphocytes in Vitro

The purpose of this study was to investigate the effect of manganese (Mn)-induced cytotoxicity on heat shock proteins in chicken spleen lymphocytes. Lymphocytes were cultured in medium in the absence and presence of MnCl₂ (2?×?10^?4, 4?×?10^?4, 6?×?10^?4, 8?×?10^?4, 10?×?10^?4, and 12?×?10^?4 mmol/L) for 12, 24, 36, and 48 h in vitro. Then, the mRNA levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were examined by real-time quantitative PCR. The results showed that the mRNA levels of HSP27, HSP40, HSP60, HSP70, and HSP90 in all treatment groups at all time points, except mRNA levels of HSP27 at 48 h, had the same tendency. As manganese concentration increased, the mRNA expression of the heat shock proteins first increased and then decreased. In other words, we demonstrated that the mRNA expression of the heat shock proteins was induced at lower concentrations of manganese and was inhibited at higher concentrations. Mn had a dosage-dependent effect on HSP27, HSP40, HSP60, HSP70, and HSP90 mRNA expression in chicken spleen lymphocytes in vitro.     

Characterization and prognosis of estrogen receptor-positive/progesterone receptor-negative male breast cancer: a population-based study

Background

The aim of this study was to explore the characteristics and prognostic information of estrogen receptor-positive/progesterone receptor-negative (ER+/PR?) male breast cancer.

Methods

Using the US National Cancer Institute’s Surveillance, Epidemiology, and End Results database, we compared the demographics, clinical characteristics, and outcome of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) patients with ER+/PR? male breast cancer patients from 1990 to 2010. Two thousand three hundred twenty-two patients with ER+/PR+ tumors and 355 patients with ER+/PR? tumors were included in our study.

Results

ER+/PR? patients were younger (P?=?0.008) and more likely to be African American (P?<?0.001) while presented with higher histological grade (P?<?0.001), larger tumor size (P?=?0.010), and more invasion to the lymph nodes (P?=?0.034) and distant sites (P?<?0.001), thus later stage (P?=?0.001). Despite higher chance of receiving chemotherapy (51.0% vs 36.5%, P?<?0.001), ER+/PR? patients experienced significantly worse breast cancer-specific survival (BSCC) (P?<?0.001) and shorter overall survival (OS) (P?=?0.003). Multivariate Cox model confirmed that tumor size, lymph node invasion, metastasis, and surgery were independent prognostic factors of both BSCC and OS for ER+/PR? male breast cancer. Age at diagnosis and chemotherapy were significantly associated with OS but not with BSCC.

Conclusion

ER+/PR? male breast cancer was more aggressive and experienced shorter survival than ER+/PR+ patients. The prognosis was mainly associated with tumor size, lymph node invasion, metastasis, and surgery.

     

Daily hypoxia increases basal monocyte HSP72 expression in healthy human subjects

Heat shock protein 72 (HSP72) performs vital roles within the body at rest and during periods of stress. In vitro, research demonstrates HSP72 induction in response to hypoxia. Recently, in vivo, an acute hypoxic exposure (75 min at 2,980 m) was sufficient to induce significant increases in monocyte expressed HSP72 (mHSP72) and a marker of oxidative stress in healthy human subjects. The purpose of the current study was to identify the impact of 10 consecutive days of hypoxic exposures (75 min at 2,980 m) on mHSP72 and erythropoietin (EPO) expression, markers of oxidative stress, and maximal oxygen consumption in graded incremental aerobic exercise. Eight male subjects were exposed to daily normobaric hypoxic exposures for 75 min at 2,980 m for 10 consecutive days, commencing and ceasing at 0930 and 1045, respectively. This stressor was sufficient to induce significant increases in mHSP72, which was significantly elevated from day 2 of the hypoxic exposures until 48 h post-final exposure. Notably, this increase had an initial rapid (30% day on day compared to baseline) and final slow phase (16% day on day compared to baseline) of expression. The authors postulate that 7-day hypoxic exposure in this manner would be sufficient to induce near maximum hypoxia-mediated basal mHSP72 expression. Elevated levels of mHSP72 are associated with acquired thermotolerance and provide cross tolerance to non-related stressors in vivo, the protocol used here may provide a useful tool for elevating mHSP72 in vivo. Aside from these major findings, significant transient daily elevations were seen in a marker of oxidative stress, alongside sustained increases in EPO expression. However, no physiologically significant changes were seen in maximal oxygen consumption or time to exhaustion.     

Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study

Background

In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up.

Methods

Twenty males and 13 females with median of age 35?years (min-max: 3–76) who underwent percutaneous renal biopsy and had diagnosis of glomerular disease (GD) were included in this retrospective study. Fifteen patients had IgAN/HSP and eighteen podocytopathy. Control group consisted of ten patients who underwent nephrectomy due to renal cancer. Dendrin expression pattern (membranous, dual, nuclear or negative), number of dendrin positive nuclei and proportion of dendrin negative glomeruli were analyzed.

Results

In GD and the control group significant differences in number of dendrin positive nuclei and proportion of dendrin negative glomeruli were found (P?=?0.004 and P?=?0.003, respectively). Number of dendrin positive nuclei was higher in podocytopathies than in IgAN/HSP, 3.90 versus 1.67 (P?=?0.028). Proportion of dendrin negative glomeruli correlated to higher rates of interstitial fibrosis (P?=?0.038), tubular atrophy (P?=?0.011) and globally sclerotic glomeruli (P?=?0.008). Dual and nuclear dendrin expression pattern were connected with lower rate of interstitial fibrosis and tubular atrophy than negative dendrin expression pattern (P?=?0.024 and P?=?0.017, respectively). Proportion of dendrin negative glomeruli correlated with lower creatinine clearance (CC) at the time of biopsy and the last follow-up (P?=?0.010 and P?<?0.001, respectively). Dendrin expression pattern correlated to CC at the last follow-up (P?=?0.009), being lower in patients with negative than nuclear or dual dendrin expression (P?=?0.034 and P?=?0.004, respectively).

Conclusion

In this pilot study the number of dendrin positive nuclei was higher in podocytopathies than in inflammatory GD. Negative dendrin expression pattern correlated to chronic tubulointerstitial changes and lower CC, which needs to be confirmed in a larger series.

     

Effects of Dietary Factors on Selenium Levels of Children to Prevent Kashin–Beck Disease During a High-Prevalence Period in an Endemic Area: a Cohort Study

Selenium (Se) supplements have been used to control Kashin–Beck disease (KBD) for decades, but the effect of diet without Se supplements is unclear because the prevalence of KBD has decreased. This matched cohort study was undertaken to determine dietary factors affecting selenium nutrition status of children living in KBD areas and the effects of Se supplements in preventing KBD. A total of 593 children aged 5–12 years were randomly selected during the high prevalence period of KBD from 1992 to 1995. Children in one village received Se supplemented (Se+) salt and were matched with three children in 16 other villages who did not receive Se supplemented (Se?) salt. A questionnaire and determinations of occipital hair Se to reflect body Se status were obtained at baseline (April 1992), at 6 months (October 1992), and yearly each April through 1995. Hair Se content in the Se+ group was significantly higher than in the Se? group (P?<?0.001) at all time-points and was significantly related to the incidence of suspected KBD symptoms (P?=?0.018). Four dietary factors significantly affected hair Se contents. Se levels were increased by consumption of Se+ salt (P?<?0.001) and eating meat/egg often (P?=?0.019) or occasionally (P?=?0.001). Se levels were decreased by consumption of grain mildewed at harvest or in storage (P?<?0.001 for each) and drinking ditch, river, or cellar water (P?<?0.001; P?=?0.002; P?<?0.001, respectively). These results show that Se+ salt had a significant effect in maintaining the Se nutrition status of children in this cohort study but that dietary factors in those without Se supplements contributed as well.     

Role of perfusion parameters on DCE-MRI and ADC values on DWMRI for invasive ductal carcinoma at 3.0 Tesla

Background

The value of apparent diffusion coefficient (ADC) values and quantitative parameters (Ktrans, Kep, Ve) in detecting prognostic factor at 3.0 Tesla remains unclear, especially in predicting prognosis of breast cancer.

Methods

A total of 151 patients with IDC underwent breast DCE-MRI and DWI-MRI at 3.0 Tesla following surgery. The ADC values were acquired with b values of 0 and 1000?s/mm². The relationship between ADC values or DCE-MRI quantitative parameters and size, histologic grade (HG), lymph node metastasis (LNM), ER, PR, and Ki67 was evaluated. The predictive values of ADC, Ktrans, Kep, and Ve to prognosis of IDC were assessed.

Results

ADC value was positively related to size (P?=?0.04) and HER2 (P?=?0.046) expression and negatively related to ER (P?=?0.012) and PR (P?<?0.001) expression. Ktrans value has positive correlation with size (P?<?0.001), HG (P?<?0.001), LNM (P?<?0.001), HER2 (P?=?0.007), and Ki67 (P?<?0.001) expression and negative correlation with ER (P?<?0.001) and PR (P?<?0.001) expression. Kep value was positively related to size (P?<?0.001) and negatively related to ER (P?<?0.001) and PR (P?<?0.001) expression. Ve value was negatively related to HER2 expression (P?=?0.004). The Cox hazard ratio (HR) of ADC, Ktrans, Kep, and Ve values on survival was 5.26 (P?=?0.093), 1.081 (P?=?0.002), 1.006 (P?=?0.941), and 0.883 (P?=?0.926), respectively.

Conclusions

Ktrans value was a best predictive indicator of HG, LNM, ER, PR, and Ki67 expression, and ADC value was the best predictive indicator of HER2. Preoperative use of the 3.0 Tesla could provide important information to determine the optimal treatment plan.