The effects of antioxidants on exercise-induced lipid peroxidation in patients with COPD

OBJEctive: The oxidant-antioxidant balance plays an important role in the pathogenesis of COPD. The aim of the present study was to evaluate the effects of exercise, as an oxidative stress factor on the oxidant-antioxidant balance and to investigate whether short-term antioxidant treatment affects lipid peroxidation products. METHODOLOGY: Twenty-one stable COPD patients and 10 control subjects were included in the study. Symptom-limited exercise tests were performed by all subjects. Blood was collected before and 1 h after exercise in control subjects and before, 1 and 3 h after exercise in COPD patients, for analysis of malondialdehyde (MDA), reduced glutathione (GSH) and vitamin E (VE) levels. VE and vitamin C treatments were added to the regular bronchodilator therapy in 10 COPD patients for 1 month. After the treatment period, an exercise test was performed and blood was collected again for MDA, GSH and VE levels. RESULTS: Baseline GSH and VE levels were significantly lower in the COPD group when compared with the control subjects. There was no statistically significant difference in MDA levels between the two groups. In the COPD group, MDA levels 3 h after exercise were significantly higher than at baseline. In contrast there were no significant differences in MDA, VE and GSH levels in the control group after exercise. VE and MDA levels increased significantly after exercise in COPD patients but there was no difference in GSH levels. Baseline exercise time was significantly lower in the COPD group than in the controls. In 10 COPD patients who were given antioxidant therapy, their exercise time increased significantly and there was no increase in MDA and VE levels after the repeated exercise test. CONCLUSIONS: Antioxidant levels were significantly lower in COPD patients than in control subjects. In these patients, exercise results in more significant oxidative stress and lipid peroxidation than in control subjects and antioxidant therapy may decrease lipid peroxidation following exercise and improve exercise capacity.     

2019 Canadian Cardiovascular Society Position Statement for Transcatheter Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) or replacement has rapidly changed the treatment of patients with severe symptomatic aortic stenosis. It is now the standard of care for patients believed to be inoperable or at high surgical risk, and a reasonable alternative to surgical aortic valve replacement for those at intermediate surgical risk. Recent clinical trial data have shown the benefits of this technology in patients at low surgical risk as well. This update of the 2012 Canadian Cardiovascular Society TAVI position statement incorporates clinical evidence to provide a practical framework for patient selection that does not rely on surgical risk scores but rather on individual patient evaluation of risk and benefit from either TAVI or surgical aortic valve replacement. In addition, this statement features new wait time categories and treatment time goals for patients accepted for TAVI. Institutional requirements and recommendations for operator training and maintenance of competency have also been revised to reflect current standards. Procedural considerations such as decision-making for concomitant coronary intervention, antiplatelet therapy after intervention, and follow-up guidelines are also discussed. Finally, we suggest that all patients with aortic stenosis might benefit from evaluation by the heart team to determine the optimal individualized treatment decision.     

Evaluation of the Relationship Between Hb F Levels and Nucleated Red Blood Cells with Morbidity in Non Transfusion-Dependent Thalassemia Patients

Recognition of risk factors of morbidities in patients with β-thalassemia intermedia (β-TI) is an important issue that must be evaluated. Non transfusion-dependent thalassemia patients referred to the outpatient clinic of Shiraz University of Medical Science, Shiraz, South Iran were enrolled in this study between 2013 and 2014. Two peripheral blood smears were prepared for evaluating developmental stage of normoblasts. One hundred and thirty-one patients with ages ranging from 3 to 42 years (mean: 23.35?±?7.9) were selected. Sixty-seven patients had at least one morbidity (51.1%). Osteoporosis and gallstones were the most common morbidities (33.6 and 24.4%, respectively). In the univariate model, hemoglobin (Hb), ferritin, Hb F, developmental stage of normoblasts and hydroxyurea (HU) therapy did not differ between patients with and without morbidity (p?>?0.05) but mean age of patients and mean number of normoblasts were higher in patients with morbidity (p?=?0.026 and p?=?0.012, respectively). In the regression model, sex and splenectomy status were different between patients with and without morbidity. It seems that females and splenectomy are risk factors for morbidity in non transfusion-dependent thalassemia patients. [Sex: odds ratio (OR)?=?2.21, 95% confidence interval (95% CI): 1.04-4.72, p?=?0.39. Splenectomy: OR = 3.10, 95% CI: 1.12-8.59, p?=?0.029.] This study shows that Hb F level and developmental stage of normoblasts does not effect the incidence of morbidities in non transfusion-dependent thalassemia patients but sex and splenectomy were effective factors in development of morbidities. Thus, splenectomy should be avoided as much as possible in patients with non transfusion-dependent thalassemia.     

Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.     

Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease.

Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5-HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa-induced dyskinesias and prolonged its antiparkinsonian response (P < or = 0.05). Under the conditions of this study, our findings suggest that 5-HT1A receptor stimulation in levodopa-treated parkinsonian patients can modulate striatal dopaminergic function and that 5-HT1A agonists may be useful as levodopa adjuvants in the treatment of PD.     

Simple fluorescence chemosensor for the detection of calcium ions in water samples and its application in bio-imaging of cancer cells

This article describes the design, synthesis and characterization of a sensor suitable for practical measurement of ionized calcium in water samples and cancer cells. Calcium is an important ion in living organs and works as a messenger in several cellular functions. A lack of Ca ions interrupts the immune system and can lead to several diseases. A novel magnetic-polydopamine nanoparticle (PDNP)/rhodamine B (RhB)/folic acid (FA) nanoparticle was developed for the determination of calcium ions in MCF 7 cell lysates and water samples. Furthermore, the produced nanoparticle was employed for bioimaging of folate receptor (FR)-overexpressed cancer cells. This nanoprobe displayed a bright photoluminescence emission at 576 nm under an excitation wavelength of 420 nm. In the presence of calcium ions, the fluorescence emission of the MNPs-PDNPs/RhB/FA probe was proportionally decreased from 20 ng mL⁻¹ to 100 ng mL⁻¹ and 0.5 μg mL⁻¹ to 20 μg mL⁻¹ with a lower limit of quantification (LLOQ) of about 20 ng mL⁻¹. The developed sensor showed a low-interference manner in the presence of possible coexistence interfering ions. In addition, this nanomaterial showed excellent biocompatibility with favorable differentiation ability to attach to the FR-positive cancer cells. The MNPs-PDNPs/RhB/FA nanoparticle has been utilized for bioimaging of the MCF 7 cell with favorable differentiation ability.

Synthesis of the MNPs-PDNPs/RhB/FA probe and application for bioimaging and Ca detection.     

Recent advances in the genetics and pathogenesis of Parkinson disease.

The identification of three genes and several additional loci associated with inherited forms of levodopa-responsive PD has confirmed that this is not a single disorder. Yet, analyses of the structure and function of these gene products point to the critical role of protein aggregation in dopaminergic neurons of the substantia nigra as the common mechanism leading to neurodegeneration in all known forms of this disease. The three specific genes identified to date--alpha-synuclein, Parkin, and ubiquitin C terminal hydrolase L1--are either closely involved in the proper functioning of the ubiquitin-proteasome pathway or are degraded by this protein-clearing machinery of cells. Knowledge gained from genetically transmitted PD also has clear implications for nonfamilial forms of the disease. Lewy bodies, even in sporadic PD, contain these three gene products, particularly abundant amounts of fibrillar alpha-synuclein. Increased aggregation of alpha-synuclein by oxidative stress, as well as oxidant-induced proteasomal dysfunction, link genetic and potential environmental factors in the onset and progression of the disease. The biochemical and molecular cascades elucidated from genetic studies in PD can provide novel targets for curative therapies.     

Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's disease and progressive supranuclear palsy

The cerebrospinal fluid (CSF) content of Met⁵-enkephalin-Arg-Gly-Leu immunoreactivity was found to be significantly decreased in patients with Huntington's disease and progressive supranuclear palsy. This peptide is derived from the proenkephalin precursor protein and normally is found in high concentrations in the basal ganglia. The decrease in CSF from Huntington's disease patients likely reflects the loss of proenkephalin-containing neurons seen in postmortem analyses of basal ganglia tissue. The decrease in progressive supranuclear palsy, a disease in which dopamine neurons degenerate but enkephalin levels in the basal ganglia are reportedly not decreased, may reflect a functional decline in enkephalinergic neuronal activity secondary to a striatal cholinergic deficit. The results suggest that a substantial portion of the CSF Met⁵-enkephalin-Arg-Gly-Leu immunoreactivity is derived from the basal ganglia and that CSF levels of this peptide can serve as an index of functional or anatomical integrity of proenkephalin synthesizing neurons in the basal ganglia.     

Experimental in vivo cross-resistance of vinca alkaloid drugs

Summary In human therapy, an absence of cross-resistance has been observed between vincristine and vindesine in patients receiving polychemotherapy whilst, in our experimental in vivo studies, such a cross-resistance has been found between Vinca alkaloids. Further studies are required to explain this discrepancy.