Effects of α-tocopherol on hemolysis and oxidative stress markers on red blood cells in ß-thalassemia major.

BACKGROUND: The accumulation of unpaired α-globin chains in patients with ß-thalassemia major may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, is a potent scavenger of lipid radicals in the membranes of red blood cells (RBCs) of patients with ß-thalassemia major. PURPOSE: To evaluate the effects of α-tocopherol on hemolysis and oxidative stress markers on the RBC membranes of patients with ß-thalassemia major. METHODS: Forty subjects included in this randomized controlled trial were allocated to the placebo and α-tocopherol groups. Doses of α-tocopherol were based on Institute of Medicine recommendations: 4-8 years old, 200 mg/day; 9-13 years old, 400 mg/day; 14-18 years old, 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4-week α-tocopherol or placebo treatment, performed before blood transfusions. RESULTS: Significant enhancements in plasma haptoglobin were noted in the α-tocopherol group (3.01 mg/dL; range, 0.60-42.42 mg/dL; P=0.021). However, there was no significant intergroup difference in osmotic fragility test results; hemopexin, malondialdehyde, reduced glutathione (GSH), or oxidized glutathione (GSSG) levels; or GSH/GSSG ratio. CONCLUSION: Use of α-tocopherol could indirectly improve hemolysis and haptoglobin levels. However, it played no significant role in oxidative stress or as an endogen antioxidant marker in ß-thalassemia major.

The Role of Serum Expression Levels of Microrna-21 on Bone Mineral Density in Hypostrogenic Postmenopausal Women with Osteoporosis: Study on Level of RANKL, OPG, TGFß-1, Sclerostin, RANKL/OPG Ratio, and Physical Activity.

BACKGROUND: MiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but other factors involved in postmenopausal osteoporosis still unknown. This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF-ß1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis (PMOP) compared with no osteoporosis (PMNOP), with point of interest on the expression of serum miR-21. METHODS: this study was conducted by comparative cross-sectional design. The subjects were divided into 2 groups of PMOP and PMNOP. We used an absolute quantification real-time PCR method to determine serum miR-21 expressions level. RESULTS: Median of serum miR-21 expression at the PMOP group was significantly higher compared to PMNOP group (p = 0.001). Serum miR-21 expression, RANKL, RANKL/OPG ratio, and physical activity were significantly correlated with BMD values in the PMOP group. Moderate physical activity was significantly negatively correlated with serum miR-21 expression. We also obtained a linear regression equation BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL (R2 = 52.5%). CONCLUSION: serum miR-21 expression in PMOP was higher compared with PMNOP. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5%. Obtained equation of BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL can explain the value of spinal BMD by 52.5%.

Role of terminal warm blood cardioplegia in complex congenital heart surgery.

Introduction Myocardial protection is vital to ensure successful open heart surgery. Cardioplegic solution is one method to achieve good myocardial protection. Inevitably, ischemia-reperfusion injury occurs with aortic crossclamping. Histidine-tryptophan-ketoglutarate solution is a frequently used cardioplegia for complex congenital heart surgery. We postulated that addition of terminal warm blood cardioplegia before removal of the aortic crossclamp might improve myocardial protection. Method A randomized controlled trial was conducted on 109 cyanotic patients aged, 1 to 5 years who underwent complex biventricular repair. They were divided into a control group of 55 patients who had histidine-tryptophan-ketoglutarate only and a treatment group of 54 who had histidine-tryptophan-ketoglutarate with terminal warm blood cardioplegia. Endpoints were clinical parameters, troponin I levels, and caspase-3 as an apoptosis marker. Results The incidence of low cardiac output syndrome was 34%, with no significant difference between groups (35.2% vs. 33.3%, p = 0.84). The incidence of arrhythmias in our treatment group was lower compared to the control group (36% vs. 12%, p = 0.005). Troponin I and caspase-3 results did not show any significant differences between groups. For cases with Aristotle score ≥ 10, weak expression of caspase-3 in the treatment group post-cardiopulmonary bypass was lower compared to the control group. Conclusion For complex congenital cardiac surgery, the addition of terminal warm blood cardioplegia does not significantly improve postoperative clinical or metabolic markers.

The role of curcumin as an inhibitor of oxidative stress caused by ischaemia re-perfusion injury in tetralogy of Fallot patients undergoing corrective surgery.

BACKGROUND: Cardiopulmonary bypass during tetralogy of Fallot corrective surgery is associated with oxidative stress, and contributes to peri-operative problems. Curcumin has been known as a potent scavenger of reactive oxygen species, which enhances the activity of antioxidants and suppresses phosphorylation of transcription factors involved in inflamation and apoptosis. OBJECTIVES: To evaluate the effects of curcumin as an antioxidant by evaluating the concentrations of malondialdehyde and glutathione, activity of nuclear factor-kappa B, c-Jun N-terminal kinase, caspase-3, and post-operative clinical outcomes. METHODS: Tetralogy of Fallot patients for corrective surgery were randomised to receive curcumin (45 mg/day) or placebo orally for 14 days before surgery. Malondialdehyde and glutathione concentrations were evaluated during the pre-ischaemia, ischaemia, re-perfusion phases, and 6 hours after aortic clamping-off. Nuclear factor-kappa B, c-Jun N-terminal kinase, and caspase-3, taken from the infundibulum, were assessed during the pre-ischaemia, ischaemia, and re-perfusion phases. Haemodynamic parameters were monitored until day 5 after surgery. RESULTS: In all the observation phases, malondialdehyde and glutathione concentrations were similar between groups. There was no significant difference in nuclear factor-kappa B activity between the groups for three observations; however, in the curcumin group, c-Jun N-terminal kinase significantly decreased from the pre-ischaemia to the re-perfusion phases, and caspase-3 expression was lower in the ischaemia phase. Patients in the curcumin group had lower temperature and better ventricular functions, but no significant differences were found in mechanical ventilation day or length of hospital stay in the two groups. CONCLUSION: Cardioprotective effects of curcumin may include inhibition of the c-Jun N-terminal kinase pathway and caspase-3 in cardiomyocytes, particularly in the ischaemia phase.

Structural and morphological changes in rat ventricular myocardium induced by chronic systemic hypoxi.

AIM: to explore the effects of chronic systemic hypoxia on myocardial structure and morphology. In addition, the goal of present study is to develop a hypoxia-induced heart failure model in rats. METHODS: Sprague-Dawley male rats, weighing 220-250 g at the time of recruitment were randomly allocated into 7 groups (n = 4 per group), the control normoxia group was exposed to room air, while the hypoxia groups were caged in a plexiglas hypoxic chamber (8% O2 and 92% N2) for 28 days. Structural and morphological changes of ventricular myocardium were determined at day 28, while blood gas parameters were measured at day 1, 3, 7, 14, 21, and 28. RESULTS: histopathologic and morphologic evaluation showed massive hypertrophy accompanied by damage of the intercalated disk (ID) structure, angiogenesis, necrosis, fibrosis, and apoptosis as a hallmark of ventricular remodeling. At the end of treatment, there were increases of LV (2.79 vs 3.71) and RV (1.72 vs 2.54) wall thicknesses, and also in hypertrophy index (from 3.19 to 5.74). Blood gas analysis revealed metabolic acidosis compensated by respiratory alkalosis. There was an observed decrease of blood gas parameters in hypoxia group compared to control group: PO2 (24.7 vs 96.4 mm Hg), PCO2 (18.2 vs 40.4 mm Hg), O2 saturation (25.5 vs 94.1 %), and HCO3 (10.1 vs 23.4 mmol/L). On the other hand an increase in hemoglobin level (221.5 vs 120.3 g/L), haematocrit level (68.6 vs 45.2 %), and red blood cell count (10.4 vs 6.9 µL/1000) could be observed. CONCLUSION: our data clearly show that chronic systemic hypoxia causes massive ventricular hypertrophy accompanied by severe structural and morphological impairment of ventricular myocardium, which eventually results in cardiac failure.

Molecular mechanism on healing process of peptic ulcer.

Ulcer healing process is an intricate and active process including reconstruction process of mucosa through formation of granulation tissue. Granulation tissue formation takes place by means of formation of ulcer base, formation of blood vessel (angiogenesis) and re-establishment of glandular architecture. The process of granulation tissue formation on the ulcer base takes place 48-72 hours after ulceration process occurs. These three phases involve various genes grouped according to their activated time, i.e. the initial response genes, intermediate response gene and late response genes. Initial response genes are activated in 30 minutes to 2 hours time, e.g EGF-R, c-fos, c-jun, egr-1, Sp-1, TFF-2/SP. Intermediate response genes are activated for 6 hours to 2 days, eg EGF, bFGF, PDGF and VEGF. Late response genes are activated for 14 days, e.g. HGF, ITF, c-met/HGF-R.