Significance of serum trace element status in patients with rheumatic heart disease

It is known that certain trace elements can affect various heart diseases. In this study, we aimed to evaluate the changes in concentrations of certain serum trace elements in patients with chronic rheumatic heart disease (RHD). Serum analysis of selenium (Se), zinc (Zn), and copper (Cu) trace elements was assayed by atomic absorption spectrophotometry. RHD patients had significantly lower serum concentrations of Se and Zn than control subjects (p<0.05 and p<0.001, respectively). However, the serum Cu concentration was significantly higher in RHD patients than in controls (1.93±0.59 μg/L vs 1.06±0.29 μg/L; p<0.001). Similarly, the Cu/Zn ratio in RHD patients was higher than in control subjects (4.70±0.92 vs 1.68±0.45; p<0.001). Additionally, no significant correlation was found among these trace element concentrations and the functional capacity classes (p>0.05). RHD patients had decreased serum Se and Zn element concentrations and increased serum Cu element concentration. We suggest that Se and Zn deficiency might be contributory factors in the development of rheumatic heart disease, and a high Cu concentration and a high Cu/Zn ratio might reflect an ongoing inflammatory process in this disease.     

The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 ± 1.5 vs. 10.9 ± 1.5), glutamine (20.5 ± 2.4 vs. 12.1 ± 1.2), and glutamate (18.3 ± 2.2 vs. 11.4 ± 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.     

Cardioprotective and Antioxidant Effects of Apomorphine

Apomorphine is a potent antioxidant that infiltrates through biological membranes. We studied the effect of apomorphine (2?μM) on myocardial ischemic-reperfusion injury in the isolated rat heart. Since iron and copper ions (mediators in formation of oxygen-derived free radicals) are released during myocardial reperfusion, apomorphine interaction with iron and copper and its ability to prevent copper-induced ascorbate oxidation were studied. Apomorphine perfused before ischemia or at the commencement of reperfusion demonstrated enhanced restoration of hemodynamic function (i.e. recovery of the work index (LVDP?×?HR) was 69.2±4.0% with apomorphine pre-ischemic regimen vs. 43.4±9.01% in control hearts, p<0.01, and 76.3±8.0% with apomorphine reperfusion regimen vs. 30.4±11.1% in controls, p<0.001). This was accompanied by decreased release of proteins in the effluent and improved coronary flow recovery in hearts treated with apomorphine after the ischemia. Apomorphine forms stable complexes with copper and with iron, and inhibits the copper-induced ascorbate oxidation. It is suggested that these iron and copper chelating properties and the redox-inactive chelates formed by transition metals and apomorphine play an essential role in post-ischemic cardioprotection.     

The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients

The effect of selenium (Se) in reducing the toxicity of cisplatin in cancer patients was studied. Forty-one patients were randomized into group A (20 patients with Se administration in first cycle of chemotherapy as study cases and without Se in second cycle of chemotherapy as control) and group B (21 patients without Se in first cycle of chemotherapy and with Se in second cycle of chemotherapy). The 400 μg per day of Se as Seleno-Kappacarrageenan were administered from 4 before to 4 d after chemotherapy for study cases. The serum Se increased from 70.4±22.86 to 157.04±60.23 ng/mL (P<0.001) in patients received Se. The cisplatin dosage was iv administration in 60–80 mg/m² on the first day. The results showed that the peripheral WBC counts on day 14 after initiation of chemotherapy in study cases was significantly higher than the controls (3.35±2.01 vs 2.31±1.38 [×10⁹L])/L,p<0.05). On the other hand, the consumption of GCSF for the cases was significantly less than the controls (110.1±82.2 vs 723.6±192.6 IU,p<0.05). The volumes of blood transfusion for the study group were also significantly less than the controls (0 vs 62±38mL,p<0.05). The nephrotoxicity of cisplatin was measured by urine enzymes (NAG, GGT, AAP, LAP, and ALP) were determined prior to and at 2, 24, 48, and 72h after initiation of chemotherapy. The urine enzymes NAG, GGT, AAP, and ALP after chemotherapy for cases were significantly lower than the controls. No toxicity of Seleno-Kappacarrageenan was noted. The above results suggest that the Se can be used as an agent for reducing the nephrotoxicity and bone marrow suppression induced by cisplatin.     

Tbx3, a transcriptional factor, involves in proliferation and osteogenic differentiation of human adipose stromal cells

Both, diabetes mellitus (DM) and hypercholesterolemia (HCH) are known as risk factors of ischemic heart disease, however, the effects of experimental DM, as well as of HCH alone, on ischemia/reperfusion-induced myocardial injury are not unequivocal. We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in rat hearts in the acute phase of DM. Our objectives were thus to extend our knowledge on how DM in combination with HCH, a model that is relevant to diabetic patients with altered lipid metabolism, may affect the size of myocardial infarction and susceptibility to arrhythmias. A combination of streptozotocin (STZ; 80 mg/kg, i.p.) and the fat–cholesterol diet (1% cholesterol, 1% coconut oil; FCHD) was used as a double-disease model mimicking DM and HCH simultaneosly occurring in humans. Following 5 days after STZ injection and FCHD leading to increased blood glucose and cholesterol levels, anesthetized open-chest diabetic, diabetic–hypercholesterolemic (DM–HCH) and age-matched control rats were subjected to 6-min ischemia (occlusion of LAD coronary artery) followed by 10 reperfusion to test susceptibility to ventricular arrhythmias in the in vivo experiments and to 30-min ischemia and subsequent 2-h reperfusion for the evaluation of the infarct size (IS) in the Langendorff-perfused hearts. The incidence of the most life-threatening ventricular arrhythmia, ventricular fibrillation, was significantly increased in the DM–HCH rats as compared with non-diabetic control animals (100% vs. 50%; p<0.05). Likewise, arrhythmia severity score (AS) was significantly higher in the DM–HCH rats than in the controls (4.9±0.2 vs. 3.5±0.5; p<0.05), but was not increased in the diabetic animals (AS 3.7±0.9; p>0.05 vs. controls). Diabetic hearts exhibited a reduced IS (15.1±3.0% of the area at risk vs. 37.6±2.8% in the control hearts; p<0.05), however, a combination of DM and HCH increased the size of myocardial infarction to that observed in the controls. In conclusion, HCH abrogates enhanced resistance to ischemia-reperfusion injury in the diabetic rat heart.     

Selenomethionine administration decreases the oxidative stress induced by post mortem ischemia in the heart,liver and kidneys of rats

Selenium is an essential element in human and animal metabolism integrated into the catalytic site of glutathione peroxidase (GPX1), an antioxidant enzyme that protects cells from damage caused by reactive oxygen species (ROS). Oxidative stress refers the imbalance between ROS and antioxidant defense systems. It generates alterations of DNA, proteins and lipid peroxidation. The imbalance occurs particularly during ischemia and lack of postmortem perfusion. This mechanism is of relevance in transplant organs, affecting their survival. The aim of this research is to evaluate the effect of seleno-methionine (SeMet) as a protective agent against postmortem ischemia injury in transplant organs. Wistar rats were orally administered with SeMet. After sacrifice, liver, heart and kidney samples were collected at different postmortem intervals (PMIs). SeMet administration produced a significant increase of Se concentration in the liver (65%, p?<?0.001), heart (40%, p?<?0.01) and kidneys (45%, p?<?0.05). Levels of the oxidative stress marker malondialdehyde (MDA) decreased significantly compared to control in the heart (0.21?±?0.04 vs. 0.12?±?0.02 mmol g^?1) and kidneys (0.41?±?0.02 vs. 0.24?±?0.03 mmol g^?1) in a PMI of 1–12 h (p?<?0.01). After SeMet administration for 21 days, a significant increase in GPX1 activity was observed in the liver (80%, p?<?0.001), kidneys (74%, p?<?0.01) and heart (35%, p?<?0.05). SeMet administration to rats significantly decreased the oxidative stress in the heart, liver and kidneys of rats generated by postmortem ischemia.

     

Relationship among serum selenium levels,lipid peroxidation,and acute bronchiolitis in infancy

Thirty-four infants with acute bronchiolitis and 25 age-matched healthy controls were enrolled to investigate the possible relationship between serum malondialdehyde (MDA) and selenium (Se) levels and the occurrence and severity of acute bronchiolitis in children. Serum samples were taken for serum Se and MDA measurements, and the clinical score was assessed at admission. Blood was taken again from the children with bronchiolitis at 2 mo after discharge from the hospital. Mean serum MDA levels were significantly higher in patients with acute bronchiolitis than at the postbronchiolitis stage and the controls (4.2±2.5nmol./L, 1.4±0.8 nmol/L, and 0.7±0.2 nmol/L, respectively [p<0.001]). Infants with bronchiolitis had lower mean serum Se levels at the acute stage than after 2 mo (31.7±28.9μg/L versus 68.4±26.4 μg/L, p<0.05, respectively); both of which were significantly lower than the control group measurements (145.0±21.9 μg/L) (p<0.001). There was a negative correlation between serum MDA and Se levels in the patient group (=−0.85, p<0.001). The age of the patient, child's immunization status, parental smoking habit, and family crowding index were not correlated with serum Se, MDA levels, or clinical score at admission. In conclusion, increased MDA levels and impaired Se status demonstrate the presence of possible relationship of these parameters with pathogenesis of acute bronchiolitis, and antioxidant supplementation with Se might be thought to supply a beneficial effect against bronchiolitis.     

Protective Effect of Na+/Ca2+ Exchange Blocker KB-R7943 on Myocardial Ischemia–Reperfusion Injury in Hypercholesterolemic Rats

Reverse-mode activation of the Na⁺/Ca²⁺ exchanger (NCX) during reperfusion following ischemia contributes to Ca²⁺ overload and cardiomyocyte injury. KB-R7943, a selective reverse-mode NCX inhibitor, reduces lethal reperfusion injury under non-ischemic conditions. However, the effectiveness of this compound under ischemic conditions is unclear. In the present study, we studied the effects of KB-R7943 in an animal model of hyperlipidemia. We further assessed whether the K _ATP ⁺ channels are involved in potential protective mechanisms of KB-R7943. Twelve rats were fed normal chow, while 48 animals were fed a high cholesterol diet. The hearts from the control and hypercholesterolemic rats were subjected to 25 min of global ischemia followed by a 120-min reperfusion. Before this, hearts from hypercholesterolemic rats either received no intervention (cholesterol control group) or were pre-treated with 1 μM KB-R7943 and 0.3 μM of K _ATP ⁺ blocker glibenclamide or glibenclamide alone. The infarction sizes (triphenyltetrazolium assay) were 35 ± 5.0 % in the control group, 46 ± 8.7 % in the cholesterol control group (p < 0.05 vs. control group), 28.6 ± 3.3 % in the KB-R7943 group (p < 0.05 vs. cholesterol control group), 44 ± 5 % in the KB-R7943 and glibenclamide group, and 47 ± 8.5 % in the glibenclamide group (p < 0.05 vs. control group). Further, KB-R7943 attenuated the magnitude of cell apoptosis (p < 0.05 vs. cholesterol control group). These beneficial effects were abolished by glibenclamide. In conclusion, diet-induced hypercholesterolemia enhances myocardial injury. Selective reverse-mode NCX inhibitor KB-R7943 reduces the infarction size and apoptosis in hyperlipidemic animals through the activation of K _ATP ⁺ channels.     

Role of CC-chemokine receptor 5 on myocardial ischemia–reperfusion injury in rats

The expression level of CC-chemokine receptor 5 (CCR5) is enhanced post inflammatory stimulations and might play a crucial role on inflammatory cells infiltration post myocardial ischemia. The purpose of this study was to evaluate the role of CCR5 on myocardial ischemia–reperfusion (I/R) injury in rats. Adult male rats were randomized to sham group, I/R group (I/R, 30 min coronary artery occlusion followed by 2-h reperfusion), ischemic preconditioning (I/R + Pre), CCR5 antibody group [I/R + CCR5Ab (0.2 mg/kg)], and CCR5 agonist group [I/R + CCR5Ago, RNATES (0.1 mg/kg)], n = 12 each group. The serum level of creatine kinase (CK) and tumor necrosis factor α (TNF-α) were measured by ELISA. Myocardial infarction size and myeloperoxidase (MPO) activity were determined. Myocardial protein expression of CCR5 and intercellular adhesion molecule-1 (ICAM-1) were evaluated by Western blotting and immunohistochemistry staining, respectively. Myocardial nuclear factor-kappa B (NF-κB) activity was assayed by electrophoretic mobility shift assay. Myocardial CCR5 protein expression was significantly reduced in I/R + Pre group (P < 0.05 vs. I/R) and further reduced in I/R + CCR5Ab group (P < 0.05 vs. I/R + Pre). LVSP and ±dP/dt _max were significantly lower while serum CK and TNF-α as well as myocardial MPO activity, ICAM-1 expression, and NF-κB activity were significantly higher in I/R group than in sham group (all P < 0.05), which were significantly reversed by I/R + Pre (all P < 0.05 vs. I/R) and I/R + CCR5Ab (all P < 0.05 vs. I/R + Pre) while aggravated by I/R + CCR5Ago (all P < 0.05 vs. I/R). Our results suggest that blocking CCR5 attenuates while enhancing CCR5 aggravates myocardial I/R injury through modulating inflammatory responses in rat heart.     

Selenium concentration in blood and hair of holstein dairy cows

Four-hundred Holstein cows in 40 dairy farms in north Greece were included in this study, and blood (n=400), black hair (n=400), white hair (n=40), and feed (n=40) samples were obtained. Although the feeding regime in these farms was similar, the selenium content of feeds was variable. The Se content of concentrate feeds was 0.104±0.086 mg/kg dry matter (DM), and of silage, it was 0.025±0.018 mg/kg. A significantly positive correlation was found between the Se concentration in black hair and the Se concentration in blood (r ²=0.610, p<0.001), the Se concentration in white hair and the Se concentration in blood (r ²=0.770, p<0.001), and the Se concentration in white hair and the Se concentration in black hair (r ²=0.921, p<0.001). The Se concentration in white hair was significantly smaller than that in black hair (p<0.001).     

Relationship of trace element,immunological markers,and HIV1 infection progression

Trace elements (selenium, zinc, copper) \gb₂ microglobulin levels, CD₄, and CD₈ cell counts have been determined in 80 HIV₁ seropositive patients. The study group consisted of 19 females and 61 males with age mean of 35±10 yr, at stage IV of infection (CDC—Atlanta classification) and treated by AZT. No severe renal or liver diseases or hypoalbuminemia were observed in this group. Se values were significantly lower than in normal adults, 48.3±17 μg/L vs 71±12 μg/L; Zn was moderately diminished, 1±0.2 mg/L vs 1.2±0.2 mg/L, whereas copper values were in the normal range, 1.2±0.3 mg/L vs 1.1±0.5 mg/L. Se or Zn deficiency was found in 60 and 30 subjects, respectively. Blood Se and Zn decreases were associated in 23 patients. Moreover, all patients showed higher \gb₂ microglobulin values than the upper normal limit of 2.4 mg/L. Negative correlations were found between Zn and \gb₂ microglobulin (p<0.005) and between Se and \gb₂ microglobulin (p<0.05). Moreover, there was a positive correlation between Se and Zn values (p<0.05). Nineteen subjects died 1 yr later (group I), and 61 remained alive (group II). With respect to the clinical evolution, a significant difference between both groups was found in Se and \gb₂ microglobulin levels as well as in CD₄ cell counts. The correlations previously observed persisted in group II, whereas no correlation was noted in group I. In addition, the patients of group I had significantly lower Se values, which were below 30 μg/L in 10 cases. These results confirm the prevalence of abnormalities in Se and Zn levels and their relationships with nonspecific markers of immune system activity in more advanced HIV disease. Impairment of trace element status and mainly Se status appeared, at least partially, to reflect the disease activity/progression and subsequently the immune dysregulation.     

Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury: role of mitochondrial ATP-sensitive potassium channels

Reperfusion injury is one of the main reasons of cardiac disease morbidity. Phytopharmaceuticals are gaining importance in modern medicine of cardioprotection because of their multiplex capacity. The aim of this study was to investigate the effect of diosgenin on the inflammatory response induced by myocardial ischemia and reperfusion injury and the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in this regard. Wistar rats (250–300 g) were used in this study. The Langendorff-perfused hearts of animals were subjected to a 30-min global ischemia followed by a 90-min reperfusion. The lactate dehydrogenase (LDH) release was measured by spectrophotometry. The levels of inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6 in the supernatant of heart’s left ventricle were measured using an enzyme-linked immunosorbent assay rat specific ELISA kit. The LDH release into the coronary effluent during reperfusion was significantly decreased, and cardiac contractility significantly improved by diosgenin preadministration as compared with those of control or Cremophor-EL (solvent of diosgenin) groups (398?±?48 vs. 665?±?65 or 650?±?73 ml/min) (P?<?0.01). Administration of diosgenin before the main ischemia significantly reduced the levels of IL-6 (P?<?0.05), IL-1β, and TNF-α (P?<?0.01) in the reperfusion phase of diosgenin-treated hearts as compared with untreated control hearts. Inhibition of mitoKATP channels by 5-hydroxydecanoate significantly reverses the cardioprotective effects of diosgenin (P?<?0.05). The findings of the present study indicate that preconditioning with diosgenin may induce cardioprotective effect against reperfusion injury through reducing the production of inflammatory mediators and activating the mitoKATP channels.     

Could Selenium Administration Alleviate the Disturbances of Blood Parameters Caused by Lithium Administration in Rats?

Lithium is widely used in medicine, but its administration can cause numerous side effects. The present study aimed at the evaluation of the possible application of selenium, an essential and antioxidant element, as a protective agent against lithium toxicity. The experiment was performed on four groups of Wistar rats: I (control)—treated with saline, II (Li)—treated with lithium (Li₂CO₃), III (Se)—treated with selenium (Na₂SeO₃) and IV (Li?+?Se)—treated with lithium and selenium (Li₂CO₃ and Na₂SeO₃) in the form of water solutions by stomach tube for 6 weeks. The following biochemical parameters were measured: concentrations of sodium, potassium, calcium, magnesium, phosphorus, iron, urea, creatinine, cholesterol, glucose, total protein and albumin and activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in serum as well as whole blood superoxide dismutase and glutathione peroxidase. Morphological parameters such as red blood cells, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets, white blood cells, neutrophils as well as lymphocytes were determined. Lithium significantly increased serum calcium and glucose (2.65?±?0.17 vs. 2.43?±?0.11; 162?±?31 vs. 121?±?14, respectively), whereas magnesium and albumin were decreased (1.05?±?0.08 vs. 1.21?±?0.15; 3.85.?±?0.12 vs. 4.02?±?0.08, respectively). Selenium given with lithium restored these parameters to values similar to those observed in the control (Ca—2.49?±?0.08, glucose—113?±?26, Mg—1.28?±?0.09, albumin—4.07?±?0.11). Se alone or co-administered with Li significantly increased aspartate aminotransferase and glutathione peroxidase. The obtained outcomes let us suggest that the continuation of research on the application of selenium as an adjuvant in lithium therapy seems warranted.     

The importance of scavenging reactive oxygen species in anti‐aging medicine

In a pilot study, we had reported on the beneficial effects of Ginkgo biloba (EGb 761) on arteriosclerotic nanoplaque formation and size in cardiovascular high‐risk patients who had undergone an aortocoronary bypass operation. Briefly, nanoplaque formation and size, the ratio oxLDL/LDL, and the highly atherothrombotic lipoprotein(a) concentration were substantially reduced, while superoxide dismutase activity and the blood concentration of the vasodilating substances cAMP and cGMP were upregulated. Since the arteriosclerosis prophylactic and well‐aging promotive impact of Ginkgo extract has been proven in this pilot study, we wanted to confirm these beneficial effects through a second observational clinical trial. The measurable variables formerly used were additionally supplemented by a wide, novel biomarker spectrum, through which the latest parameters and markers of plaque stability and progression, oxidative stress, and inflammation were available. In eleven patients with metabolic syndrome in the initial stage, the reduction of arteriosclerotic nanoplaque formation amounted to 14.3±2.9% (p<0.0077) and of nanoplaque size to 23.4±3.7% (p<0.0004), respectively, after 2‐months of treatment with Ginkgo biloba extract. Additionally, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were upregulated by 19.6±10.0% (p<0.0785) and 11.6±2.3% (p<0.001), respectively, the quotient oxLDL/LDL lowered by 21.0±4.3% (p<0.002), and lipoprotein(a) concentration decreased by 26.3±4.8% (p<0.001) in the patients' blood. The concentration of cAMP and cGMP was augmented by 43.5±12.0% (p<0.001) and 32.9±10.4% (p<0.001), respectively. Surprisingly, we found a lowering of the serum Ca²⁺ concentration by 5.4±1.6% (p<0.0076) from 2.37±0.03 to 2.24±0.04 mmol/L (p<0.0069). Apart from an additional vasodilatory effect, the lowered extracellular Ca²⁺ concentration affects nanoplaque formation restrictively, since this is a Ca²⁺ driven process. Furthermore, we could show a favourable development of the biomarkers 8‐iso‐PGF_2α, oxLDL/LDL, SOD, GPx (oxidative stress), hs‐CRP, MPO, TNFα, TGFβ₁ (inflammatory status) and MMP‐9 (plaque stability). The markers selected here are suited to provide a comprehensive risk profile for the prevention of arteriosclerosis. Finally, a multiple regression analysis reveals a basis for a mechanistic explanation of nanoplaque reduction under Ginkgo treatment. The arteriosclerosis inhibiting effect is due to an attenuation of the risk factors oxLDL/LDL, Lp(a), and [Ca²⁺]_o as well as to a significant increase in the vasodilator cAMP and cGMP concentration. Thus, Ginkgo with its pleiotropic effects should be assigned a fixed rank among the anti‐aging medical therapeutics as a prophylactic measure, especially in patients with early‐stage metabolic syndrome.     

Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of PI3-K, mTOR, GSK-3β, and apoptosis

Post-conditioning by repetitive cycles of reperfusion/ischemia after prolonged ischemia protects the heart from infarction. The objectives of this study were: Are kinases (PI3-kinase, mTOR, and GSK-3β) involved in the signaling pathway of post-conditioning? Does post-conditioning result in a diminished necrosis or apoptosis? In open chest rats the infarct size was determined after 30 min of regional ischemia and 30 min of reperfusion using propidium iodide and microspheres. Post-conditioning was performed by three cycles of 30 s reperfusion and reocclusion each, immediately upon reperfusion. PI3-kinase and mTOR were blocked using wortmannin (0.6 mg/kg) or rapamycin (0.25 mg/kg), respectively. The phosphorylation of GSK-3β and p70S6K was determined with phospho-specific antibodies. TUNEL staining and detection of apoptosis-inducing factor (AIF) were used for the determination of apoptosis. Control hearts had an infarct size of 49 ± 3%, while post-conditioning significantly reduced it to 29 ± 3% (P < 0.01). Wortmannin as well as rapamycin completely blocked the infarct size reduction of post-conditioning (51 ± 2% and 54 ± 5%, respectively). Western blot analysis revealed that post-conditioning increased the phosphorylation of GSK-3β by 2.3 times (P < 0.01), and this increase could be blocked by wortmannin, a PI3-kinase inhibitor. Although rapamycin blocked the infarct size reduction, phosphorylation of p70S6K was not increased in post-conditioned hearts. After 2 h of reperfusion, the post-conditioned hearts had significantly fewer TUNEL-positive nuclei (35 %) compared to control hearts (53%; P < 0.001). AIF was equally reduced in post-conditioned rat hearts (P < 0.05 vs. control). Infarct size reduction by ischemic post-conditioning of the in vivo rat heart is PI3-kinase dependent and involves mTOR. Furthermore, GSK-3β, which is thought to be a regulator of the mPTP, is part of the signaling pathway of post-conditioning. Finally, apoptosis was inhibited by post-conditioning, which was shown by two independent methods. The role of apoptosis and/or autophagy in post-conditioning has to be further elucidated to find therapeutic targets to protect the heart from the consequences of acute myocardial infarction.     

Ovariectomy Reinstates the Infarct Size-Limiting Effect of Postconditioning in Female Rabbits

Gender seems to interfere with the cardioprotective effect of ischemic preconditioning (PreC) and postconditioning (PostC); PreC-conferred protection is weaker or lost in female animals after ovariectomy (Ov), while the role of PostC is still in dispute. We sought to investigate the effect of PostC in female rabbits, its interaction with Ov, and the potential implicated intracellular pathways. Intact or Ov adult female rabbits (n = 46) were subjected to 30 min ischemia and reperfusion with PostC (PostC or OvPostC), which consisted of six cycles of 30-s ischemia/30-s reperfusion at the end of ischemia, or without PostC (Fem or OvFem). Infarct size (I) and area at risk (R) were determined by TTC staining and fluorescent particles, respectively, after 3-h reperfusion in 30 out of 46 animals. Plasma levels of estradiol and nitrite/nitrate (NO _x ) were evaluated. ERKs, p38-MAPK, and Akt assessment was performed in excised hearts 1-min after starting the final reperfusion period in the remaining 16 animals. Infarct size was significantly reduced only in OvPostC group (I/R ratio, 25.3 ± 2.7, vs 48.1 ± 2.0, 43.6 ± 4.2 and 55.1 ± 5.6 % in Fem, OvFem, and PostC groups, p < 0.05). In ovariectomized rabbits, plasma estradiol and NO _x levels were lower than in the normal ones. Akt phosphorylation in ischemic regions was significantly higher in OvPostC group, whereas ERK1/2 and p38-MAPK activation was observed in all ovariectomized animals irrespective of PostC. PostC is not effective in female rabbits, but the protection is reinstated after Ov potentially via the RISK pathway.     

Selenium-methionine and chromium-methionine supplementation of sheep around parturition: impacts on dam and offspring performance

To examine the effects of maternal energy restriction along with selenium-methionine (Se-Met) and chromium-methionine (Cr-Met) supplementation on performance of pregnant sheep and their offspring, the following treatments were allotted randomly to 40 multiparous Baluchi ewes (53.9 ± 1.15 kg of body weight [BW]) from 5 weeks prior to 5 weeks after parturition: (1) Control diet (60% and 100% of NRC energy requirements in pre- and post-partum, respectively); (2) Control diet plus 5 mg Se-Met/kg dry matter (DM); (3) Control diet plus 3 mg Cr-Met/kg DM and (4) Control diet plus 5 mg Se-Met and 3 mg Cr-Met/kg DM (Se–Cr-Met) of concentrate diet. The results indicated that Cr-Met alone or in combination with Se-Met increased average DM intake of ewes. In addition, Group Cr-Met had higher average BW than the Control (p < 0.05). Se-Met and/or Cr-Met supplementation led to decreased average serum cholesterol of the ewes (p < 0.05). Groups Cr-Met and Se–Cr-Met displayed decreased average serum malondialdehyde compared to the Control (p < 0.05). At 24 h post-partum, Group Se–Cr-Met had a greater serum Se content than the Control (p = 0.006). Compared with the Control, the Se concentration in milk was significantly increased from 30 to 138 µg/l and 197 µg/l in Groups Se-Met and Se–Cr-Met, respectively (p < 0.01), which proved that Se-Met supplementation can increase the Se concentration of ewe milk. Furthermore, feeding Cr-Met may attenuate BW loss post-partum and Se-Met and/or Cr-Met supplements may ameliorate oxidative stress condition in ewes around parturition.     

Chronic treatment with statins increases the availability of selenium in the antioxidant defence systems of hemodialysis patients

ProjectOxidative stress (OS) is enhanced in hemodialysis (HD) patients. Lipid peroxidation and oxidative damage to glycids, proteins and nucleic acids are the main consequences of OS and are associated with increased cardiovascular risk. Vitamin E and glutathione peroxidase (GSH-Px) represent the main antioxidant systems in human cells. Selenium (Se), bound to the active sites of GSH-Pxs, plays a critical role in this antioxidant defence system. Statins are widely used and extensively investigated in the prevention of cardiovascular disease, notably in high-risk subjects. Several studies show antioxidant effects of statins not related to their lipid-lowering action. Our study aimed to compare serum Se concentration in ESRD patients on maintenance HD and in homogeneous healthy subjects and to investigate whether chronic treatment with statins may interfere with serum Se concentration in HD patients.ProcedureA total of 103 HD patients and 69 healthy subjects were enrolled; HD patients were divided into patients who were not treated with statins (group A) and patients who assumed statins since 6 months at least (group B). Serum Se was determined by atomic absorption spectrometry.ResultsSerum Se was significantly lower in HD patients of group A compared with healthy subjects (81.65±19.66 Vs. 96.47±15.62 mcg/L, p<0.0040). However, in HD patients who assumed statins serum, Se was significantly higher than in HD patients who did not (111.83±18.82 vs. 81.65±19.66 mcg/L, p<0.0001).ConclusionsOur results suggest that in HD patients chronic treatment with statins is related to higher-serum Se concentration.     

Different bioavailability in humans of wheat and fish selenium as measured by blood platelet response to increased dietary Se

The bioavailabilities of selenium (Se) from Se-rich fish species and Se-rich wheat were compared in a study involving 32 healthy volunteers. Initial serum Se values were 109±16 μg/L (mean±SD). For 6 wk, one group (n=11) included Se-rich bread in their diet, bringing daily average intake of Se up to 135±25 μg/d. Another group (n=11) consumed Se-rich fish daily (average Se intake: 115±31 μg/d), whereas the control group (n=10) ate their normal diet, providing 77±25 μg Se/d. Serum Se increased by 17% (P<0.01), and platelet Se increased by 30% (P<0.01) in the wheat group. Although platelet Se decreased by 11% in the fish group, no changes in serum and platelet Se in the fish or control group reached statistical significance. Glutathione peroxidase (EC 1.11.1.9; GSH-Px) activity in serum and platelets did not change during the study, nor did platelet mercury (Hg) content. Since the dietary intake of Hg, arsenium (As), and fatty acids could not satisfactorily explain the lack of response in the fish group, the results are indicative of low bioavailability of fish Se in humans. At present, wheat Se seems to be the most important factor contributing to the body stores of Se in this study population. Dr. Norheim died on January 9, 1991.