The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq ¹³¹Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p?<?0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p?<?0.05). A significant decrease in the control group (p?<?0.05) and increase in group 4 (p?<?0.05) were observed in GSH level after RAIT (p?<?0.05). Mean variation of GSH was significant between control group with groups 3 (p?<?0.01) and 4 (p?<?0.01). The results indicate that activity of SOD remained unchanged in all groups (p?>?0.05). A significant increase was observed in CAT activity after RAIT in all groups (p?<?0.05), which was higher in control group than intervention groups. In groups 3 (p?<?0.05) and 4 (p?<?0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.     

Serum Trace Elements and Electrolytes Are Associated with Fasting Plasma Glucose and HbA<Subscript>1c</Subscript> in Postmenopausal Women with Type 2 Diabetes Mellitus

The primary aim of the research was to assess the level of trace elements and electrolytes in serum of postmenopausal diabetic women. Sixty-four postmenopausal women with type 2 diabetes mellitus (DM2) and 64 age- and body mass index-matched controls were examined. Serum trace elements were assessed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Fasting plasma glucose (FPG) and glycated hemoglobin (HbA_1c) levels were evaluated using Randox kits. The obtained data demonstrate that DM2 patients were characterized by 42 and 34 % higher FPG and HbA_1c levels, respectively (p < 0.001). The level of Cu and Se in diabetic postmenopausal women was increased by 10 and 15 % in comparison to the respective control values (p = 0.002 and <0.001). Serum Mn, Zn, and Ni concentrations were lower than the control ones by 32 % (p = 0.003), 8 % (p = 0.003), and 23 % (p = 0.046), respectively. FPG and HbA_1c levels directly correlated with serum Se (p < 0.001) and Cu (p = 0.014 and p = 0.028) concentrations and inversely related to Zn (p < 0.001) and Tl (p = 0.023 and p = 0.029) levels. Multiple regression analysis demonstrated a significant association between serum Zn and Se and FPG and HbA_1c levels. It is proposed that Zn and Se play an important role in DM2 pathogenesis. Further studies are required to assess the intimate mechanisms of the observed differences.     

Protein malnutrition during fetal programming induces fatty liver in adult male offspring rats

We evaluated the effects of protein malnutrition on liver morphology and physiology in rats subjected to different malnutrition schemes. Pregnant rats were fed with a control diet or a low protein diet (LPD). Male offspring rats received a LPD during gestation, lactation, and until they were 60 days old (MM group), a late LPD that began after weaning (CM), or a LPD administrated only during the gestation-lactation period followed by a control diet (MC). On day 60, blood was collected and the liver was dissected out. We found a decrease in MM rats’ total body (p < 0.001) and liver (p < 0.05) weight. These and CM rats showed obvious liver dysfunction reflected by the increase in serum glutamic pyruvic transaminase (SGOT) (MM p < 0.001) and serum glutamic pyruvic transaminase (SGPT) (MM and CM p < 0.001) enzymes, and liver content of cholesterol (MM and CM p < 0.001) and triglycerides (MM p < 0.01; CM p < 0.001), in addition to what we saw by histology. Liver dysfunction was also shown by the increase in gamma glutamyl transferase (GGT) (MM, MC, and CM p < 0.001) and GST-pi1 (MM and CM p < 0.001, MC p < 0.05) expression levels. MC rats showed the lowest increment in GST-pi1 expression (MC vs. MM; p < 0.001, MC vs. CM; p < 0.01). ROS production (MM, CM, and MC: p < 0.001), lipid peroxidation (MM, CM, and MC p < 0.001), content of carbonyl groups in liver proteins (MM and CM p < 0.001, MC p < 0.01), and total antioxidant capacity (MM, CM, and MC p < 0.001) were increased in the liver of all groups of malnourished animals. However, MM rats showed the highest increment. We found higher TNF-α (MM and CM p < 0.001), and IL-6 (MM and CM p < 0.001) serum levels and TGF-β liver content (MM p < 0.01; CM p < 0.05), in MM and CM groups, while MC rats reverted the values to normal levels. Pro-survival signaling pathways mediated by tyrosine or serine/threonine kinases (pAKT) (MM and CM p < 0.001; MC p < 0.01) and extrasellular signal-regulated kinase (pERKs) (MM p < 0.01; CM p < 0.05) appeared to be activated in the liver of all groups of malnourished rats, suggesting the presence of cells resistant to apoptosis which would become cancerous. In conclusion, a LPD induced liver damage whose magnitude was related to the developmental stage at which malnutrition occurs and to its length.     

Determination of Micronutrients and Oxidative Stress Status in the Blood of STZ-Induced Experimental Diabetic Rat Models

This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3–4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p < 0.005). Retinol levels decreased significantly in STZ groups (p < 0.005). In the groups administered 55 mg/kg STZ ferrum and vitamin C levels were found significantly lower than the other groups (p < 0.005). In the group given 65 mg/kg STZ α-tocopherol levels were highest (p < 0.005) among other groups. There was not any difference between the groups for MDA, Cu/Zn, and Mg. For both doses, oxidative stress status was not significantly affected within 48 h of the application, however, some micronutritents were affected significantly.     

Quercetin and Vitamin C Mitigate Cobalt Chloride-Induced Hypertension through Reduction in Oxidative Stress and Nuclear Factor Kappa Beta (NF-Kb) Expression in Experimental Rat Model

The objective of the present work was to evaluate the toxic effects of cobalt chloride, a potent oxidative stress-inducing chemical, at 650 ppm in rats and the protective effect of quercetin and/or vitamin C against the cobalt chloride-induced toxicity. Thirty rats were randomly selected, and assigned to one of five groups: control, cobalt chloride, cobalt chloride + quercetin, cobalt chloride + vitamin C and cobalt chloride + quercetin + vitamin C. The exposure of rats to cobalt chloride led to a significant increase (p < 0.05) in malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) generated, but decreased nitric oxide (NO) bioavailability. Also, significant (p < 0.05) reductions were observed in the activity of glutathione peroxidase (GPx) and reduced glutathione (GSH) content in the cardiac and renal tissues. Treatment with quercetin and vitamin C reversed the effect of cobalt chloride on MDA, H₂O₂ and NO, more potently than with either of the two antioxidants, and increased the antioxidant defence system. Further, treatment of rats with quercetin and vitamin C in combination resulted in significant (p < 0.05) decreases in the systolic, diastolic, and mean arterial blood pressure of rats, relative to those exposed to cobalt chloride alone. Immunohistochemical studies revealed a greater expression of nuclear factor kappa beta (NF-kB) in the cobalt chloride group compared with the control- and antioxidants-treated rats. The results of this study suggest a protective role for quercetin and vitamin C in the amelioration of the toxic mechanisms leading to cobalt chloride-induced hypertension and its associated cardiac and renal complications in rats.     

Interleukin-6 and C-reactive protein,successful aging,and mortality: the PolSenior study

Background

In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly.

Results

IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n?=?3496 individuals, p?<?0.001 and CRP: n?=?3632, p?=?0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n?=?1258, p?<?0.001 and CRP: n?=?1312, p?<?0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n?=?2238, p?<?0.001 and CRP: n?=?2320, p?=?0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p?<?0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p?<?0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR?=?1.063 per each pg/mL, 95 % CI: 1.052-1.074, p?<?0.001 and HR?=?1.020 per each mg/L, 95 % CI: 1.015-1.025, p?<?0.001, respectively) but also in the successfully aging subgroup (HR?=?1.163 per each pg/mL, 95 % CI: 1.128-1.199, p?<?0.001 and HR?=?1.074 per each mg/L, 95 % CI: 1.047-1.100, p?<?0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p?<?0.001).

Conclusions

Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.

     

Glutamate receptors of the A5 region modulate cardiovascular responses evoked from the dorsomedial hypothalamic nucleus and perifornical area

To assess the possible function of glutamate in the interaction between the dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine region (A5), cardiovascular and respiratory changes were studied in response to electrical stimulation of the DMH-PeF (1 ms pulses, 30–50 μA given at 100 Hz for 5 s) before and after the microinjection of kynurenic acid (non-specific glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist; 50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region. DMH-PeF electrical stimulation elicited a pressor (p <?0.001) and tachycardic response (p <?0.001) which was accompanied by an inspiratory facilitation characterised by an increase in respiratory rate (p <?0.001) due to a decrease in expiratory time (p <?0.01). Kynurenic acid within the A5 region decreased the tachycardia (p <?0.001) and the intensity of the blood pressure response (p <?0.001) to DMH-PeF stimulation. After the microinjection of MK-801 and CNQX into the A5 region, the magnitude of the tachycardia and the pressor response were decreased (p <?0.05 and p <?0.01; p <?0.001 and p <?0.05, respectively). After MCPG microinjection into the A5 region, a decrease in the tachycardia (p <?0.001) with no changes in the pressor response was observed during DMH-PeF stimulation. The respiratory response elicited by DMH-PeF stimulation was not changed after the microinjection of kynurenic acid, MK-801, CNQX or MCPG within the A5 region. These results suggest that A5 region glutamate receptors play a role in the cardiovascular response elicited from the DMH-PeF. The possible mechanisms involved in these interactions are discussed.     

The Differences in the Cellular and Plasma Antioxidative Capacity Between Transient and Defined Focal Brain Ischemia: Does it Suggest Supporting Time-Dependent Neuroprotection Therapy?

There are many opened questions about the precocious role of oxidative stress in the physiopathology of the early stage of transitory ischemic attack (TIA) and defined focal brain ischemia, as well as about its correlation with clinical severity, short-lasting and clinical outcome prediction in these conditions. The study evaluates the values of glutathione (GSH), glutathione peroxidase, and superoxide dismutase (SOD) in hemolysates and total thiol content (–SH), advanced oxidation protein products (AOPP), SOD, and malondialdehyde (MDA) in plasma, in TIA and stroke patients in the early stage of their neurological onset. The results are interpreted in view of the potential relationship between tested parameters and clinical severity and clinical outcome prediction. Better hemolysates’ and total antioxidant profile with higher values of AOPP were observed in TIA compared to stroke patients (p < 0.05). The stroke patients with initially better clinical presentation showed better antioxidant profile with lower values of AOPP (p < 0.05). In TIA patients, this was observed for GSH, –SH content, and AOPP (p < 0.05), which correlated with a short risk for stroke occurrence in this group (p < 0.01). Beyond MDA values, all tested parameters showed correlation with clinical outcome in stroke patients (p < 0.05). The measurement of oxidative stress in TIA and stroke patients would be important for identifying patients’ subgroups which might receive supporting therapy providing better neurological recovery and clinical outcome. That approach might give us an additional view of a short-lasting risk of stroke occurrence after TIA, and its clinical outcome and prognosis.     

Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet

The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5–9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B₁₂ and a significantly higher intake of vitamin C (p < 0.05) compared with non-vegetarians. Hematologic parameters and serum iron concentrations were within the reference range in both groups of children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p < 0.01) lower in vegetarians than in omnivores. In children on a vegetarian diet, median hepcidin levels were lower (p < 0.05) but sTfR concentrations significantly higher (p < 0.001) compared with omnivorous children. In the multivariate regression model, we observed associations between hepcidin level and ferritin concentration (β = 0.241, p = 0.05) in the whole group of children as well as between hepcidin concentration and CRP level (β = 0.419, p = 0.047) in vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.     

Elemental Analysis of Whole and Protein Separated Blood Serum of Patients with Systemic Lupus Erythematosus and Sjögren’s Syndrome

Data on the effects of selenium supplementation on clinical signs and metabolic profiles in women at risk for intrauterine growth restriction (IUGR) are scarce. This study was designed to assess the effects of selenium supplementation on clinical signs and metabolic status in pregnant women at risk for IUGR. This randomized double-blind placebo-controlled clinical trial was performed among 60 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to intake either 100 μg selenium supplements as tablet (n = 30) or placebo (n = 30) for 10 weeks between 17 and 27 weeks of gestation. After 10 weeks of selenium administration, a higher percentage of women in the selenium group had pulsatility index (PI) of <1.45) (P = 0.002) than of those in the placebo group. In addition, changes in plasma levels of total antioxidant capacity (TAC) (P < 0.001), glutathione (GSH) (P = 0.008), and high-sensitivity C-reactive protein (hs-CRP) (P = 0.004) in the selenium group were significant compared with the placebo group. Additionally, selenium supplementation significantly decreased serum insulin (P = 0.02), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), and homeostatic model assessment for B-cell function (HOMA-B) (P = 0.02) and significantly increased quantitative insulin sensitivity check index (QUICKI) (P = 0.04) and HDL-C levels (P = 0.02) compared with the placebo. We did not find any significant effect of selenium administration on malondialdehyde (MDA), nitric oxide (NO), fasting plasma glucose (FPG), and other lipid profiles. Overall, selenium supplementation in pregnant women at risk for IUGR resulted in improved PI, TAC, GSH, hs-CRP, and markers of insulin metabolism and HDL-C levels, but it did not affect MDA, NO, FPG, and other lipid profiles.Clinical trial registration number http://www.irct.ir: IRCT201601045623N64.     

Factors Influencing Non-<Emphasis Type="Italic">albicans</Emphasis> Candidemia: A Case–Case–Control Study

The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case–case–control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.     

Evaluation of Mineral Concentrations in Maternal Serum Before and After Birth and in Newborn Cord Blood Postpartum—Preliminary Study

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2–8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 μg/ml; p < 0.007), Fe (1.08 ± 0.46 vs 0.82 ± 0.35 μg/ml; p < 0.0004), and Zn (0.63 ± 0.17 vs 0.46 ± 0.16; p < 0.0001) in maternal serum was found after delivery. Moreover, higher levels of Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca: 102.80 ± 7.80 μg/ml; p < 0.0001, Fe: 1.96 ± 0.43 μg/ml; p < 0.0001, Zn: 0.65 ± 0.16 μg/ml; p < 0.0001, Cu: 0.36 ± 0.09 μg/ml; p < 0.0001) and in the umbilical artery cord blood (Ca: 98.07 ± 8.18 μg/ml; p < 0.0001, Fe: 1.63 ± 0.30 μg/ml; p < 0.0001, Zn: 0.65 ± 0.15 μg/ml; p < 0.0001, and Cu: 0.36 ± 0.10 μg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 ± 10.76 μg/ml, Fe: 0.82 ± 0.35 μg/ml, Zn: 0.46 ± 0.16 μg/ml, and Cu: 1.90 ± 0.35 μg/ml). Fe levels in the cord artery serum negatively correlated with blood loss during delivery (R = ?0.48; p = 0.01), while the Ca concentration in the maternal serum after birth decreased with the age of the women (R = ?0.25; p = 0.03). In conclusion, it seems that the process of birth alters the mineral levels in pregnant women’s blood. Moreover, it was found that blood loss and the age of the mother are associated with mineral concentrations in the maternal serum and cord artery blood.     

Impact of neutrophil-to-lymphocyte ratio on periprocedural myocardial infarction in patients undergoing non-urgent percutaneous coronary revascularisation

Background

Pro-thrombotic conditions importantly influence myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). The neutrophil-to-lymphocyte ratio (NLR) has emerged as a predictor of cardiovascular events and of long-term prognosis, especially in ST-elevation myocardial infarction patients undergoing primary PCI. The aim of our study was to evaluate the role of NLR on periprocedural myocardial infarction (MI) in patients undergoing non-urgent PCI.

Methods

In a consecutive cohort of 1542 patients undergoing PCI, myonecrosis biomarkers were determined at 6, 12, 24 and 48 hours post-procedure. Patients were divided into quintiles according to NLR values. Periprocedural myonecrosis was defined as a troponin I increase of 3 times the upper limit of normal or as 50?% of an elevated baseline value, whereas periprocedural MI was defined as a CK-MB increase of 3 times the upper limit of normal or 50?% of baseline.

Results

Higher NLR was related to age, established risk factors and cardiovascular history. NLR was associated with severe coronary artery disease (p = 0.009), tighter stenosis (p < 0.001), coronary calcifications (p = 0.005), intracoronary thrombus or thrombectomy use (p < 0.001), TIMI flow pre- and post-PCI (p < 0.001), and inversely to restenosis (p = 0.04) and use of a drug-eluting stent (p = 0.001). NLR did not influence the occurrence of myonecrosis (p = 0.75; adjusted OR (95?% CI) = 0.99 (0.63–1.54), p = 0.96), but was associated with a higher occurrence of periprocedural MI, even after correction for baseline differences (p = 0.03; adjusted OR (95?% CI) = 1.33 (1.02–2.3), p = 0.02), with NLR ≥ 3 best predicting the risk of periprocedural MI at the receiver operating characteristic curve analysis.

Conclusion

In patients undergoing non-urgent PCI, a higher NLR increases the risk of periprocedural MI, especially for values ≥ 3.

     

Lutein protects against β-amyloid peptide-induced oxidative stress in cerebrovascular endothelial cells through modulation of Nrf-2 and NF-κb

In the present study, we determined the protective role of lutein against Aβ _25–35 peptide-induced oxidative stress and apoptosis in bEND.3 cells. Cell viability was determined through MTT assay. Reactive oxygen species, lipid peroxides, and antioxidant enzyme activities were evaluated to analyze the oxidative stress status. NF-κB and Nrf-2 downstream target protein expressions were determined through western blot. Apoptosis was analyzed through caspase activities and subG1 accumulation. The results showed that Aβ _25–35 significantly increased (p < 0.001) oxidative stress biomarkers. Aβ _25–35 significantly up-regulated NF-κB nuclear expression and down-regulated Nrf-2 levels and HO-1 and, NQO-1 expressions. Aβ _25–35 induced apoptosis through decreasing mitochondrial membrane potential and increasing caspase 9 and 3 activities. Lutein pre-treatment significantly (p < 0.001) improved cell viability and decreased ROS levels (p < 0.001) and lipid peroxidation (p < 0.01). Lutein prevented Aβ _25–35-induced NF-κB nuclear expressions and up-regulated Nrf-2 expressions. Further, lutein also improved mitochondrial membrane potential and down-regulated caspase activities and subG1 accumulation. The present study shows the protective role of lutein against Aβ _25–35-induced toxicity by modulating Nrf-2 and NF-κB expressions in cerebrovascular endothelial cells.     

Effects of VEGF levels on anti-VEGF therapy for patients with idiopathic choroidal neovascularization

The objective of this study is to investigate the levels of vascular endothelial growth factor (VEGF) and other cytokines in aqueous humor of patients with idiopathic choroidal neovascularization (CNV) and their effects together with central retinal thickness (CRT) on the response to intravitreal injection of anti-VEGF antibody ranibizumab. This clinical study recruited 32 eyes from 32 patients with CNV under or besides fovea. VEGF, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 levels were detected in aqueous humor (0.1 ml) sampled during intravitreal injection. Aqueous humor controls were from nine cataract patients without any systemic disorders. The VEGF levels in aqueous humor were negatively related (r = ?0.373, p = 0.035) to CRT, which was positively related (r = 0.743, p < 0.001) to the number of injections. The VEGF levels before treatment and during the third injection in four patients with three or more injections were 13.42 ± 8.50 and 5.75 ± 3.68 (p = 0.055), respectively. The average best corrected visual acuity (BCVA) before and 12 months after treatment were 57.03 ± 16.15 and 75.16 ± 11.78 (p < 0.001), and the average CRT before and 12 months after treatment were 352.09 ± 84.15 and 251.13 ± 63.96 (p < 0.001), respectively. The visual improvement was negatively related (r = ?0.815, p < 0.001) to the visual baseline, and the vision 12 months after treatment was positively related (r = 0.581, p < 0.001) to that before treatment. No severe ocular or systemic complication appeared during treatment and follow-ups for all the patients. Intravitreal injection of anti-VEGF antibody ranibizumab is safe and effective for the treatment of idiopathic CNV through decreasing CRT. The patients with larger CRT baseline need more injections of ranibizumab.     

Characterization of <Emphasis Type="Italic">Gladiolus</Emphasis> Germplasm Using Morphological,Physiological, and Molecular Markers

Estimation of variability and genetic relationships among breeding materials is one of the important strategies in crop improvement programs. Morphological (plant height, spike length, a number of florets/spike), physiological (chlorophyll content, chlorophyll fluorescence, and rapid light curve parameters) and Directed amplification of minisatellite DNA (DAMD) markers were used to investigate the relationships among 50 Gladiolus cultivars. Cluster analysis based on morphological data, physiological characteristics, molecular markers, and cumulative data discriminated all cultivars into seven, five, seven, and six clusters in the unweighted pair-group method using arithmetic mean (UPGMA) dendrogram, respectively. The results of the principal coordinate analysis (PCoA) also supported UPGMA clustering. Variations among the Gladiolus cultivars at phenotypic level could be due to the changes in physiology, environmental conditions, and genetic variability. DAMD analysis using 10 primers produced 120 polymorphic bands with 80% polymorphism showing polymorphic information content (PIC = 0.28), Marker index (MI = 3.37), Nei’s gene diversity (h = 0.267), and Shannon’s information index (I = 0.407). Plant height showed a positive significant correlation with Spike length and Number of florets/spike (r = 0.729, p < 0.001 and r = 0.448, p = 0.001 respectively). Whereas, Spike length showed positive significant correlation with Number of florets/spike (r = 0.688, p < 0.001) and Chlorophyll content showed positive significant correlation with Electron transport rate (r = 0.863, p < 0.001). Based on significant morphological variations, high physiological performance, high genetic variability, and genetic distances between cultivars, we have been able to identify diverse cultivars of Gladiolus that could be the potential source as breeding material for further genetic improvement in this ornamental crop.     

Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats

The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P?<?0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (?18 %), hematocrit (Ht) (?18 %), hemoglobin content (Hb) (?36 %), mean corpuscular hemoglobin (MCH) (?17 %), and mean corpuscular hemoglobin concentration (MCHC) (?16 %). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42 % (P?<?0.01), 134 % (P?<?0.001), 27.5 % (P?<?0.01), 147 % (P?<?0.001), and 67 % (P?<?0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.     

Diagnosis of takotsubo cardiomyopathy is increasing over time in patients presenting as ST-elevation myocardial infarction

Background

Takotsubo cardiomyopathy often presents with the clinical signs of ST-elevation myocardial infarction (STEMI). The increase in scientific publications addressing this relatively rare condition may result in higher awareness and diagnosis of takotsubo cardiomyopathy.

Aim

To assess the observed prevalence per year of takotsubo cardiomyopathy in a large registry of patients with STEMI, during a 12-year inclusion period.

Method

All patients presenting with STEMI at a large regional cardiology clinic were entered into a database (n = 8,413, mean age 63 ± 13 years). Takotsubo cardiomyopathy was diagnosed in 42 patients (0.5?%). Years of evaluation were defined as ‘early years’ (January 2002 to December 2007; n = 4350) and ‘later years’ (January 2008 to December 2013). Multivariable analyses were performed to adjust for differences in demographical and clinical variables.

Results

In later years, the age of STEMI patients was slightly higher (64 ± 13 vs. 63 ± 13 years, p < 0.001), with more patients with clinical symptoms of shock (10 vs. 7?%, p < 0.001) or a history of percutaneous coronary intervention or hypertension (10 vs. 8?%, p = 0.001 and 37 vs. 34?%, p < 0.001). Smoking and a positive family history were less often observed during later years (39 vs. 46?%, p < 0.001 and 37 vs. 42?% p < 0.001). Patients with takotsubo cardiomyopathy were more often female (81 vs. 27?%, p = 0.001). Takotsubo cardiomyopathy was more often diagnosed in the later period (0.7 vs. 0.3?%, OR 2.4, 95?% CI 1.2–4.6, p = 0.009). The higher prevalence of takotsubo cardiomyopathy in recent years remained significant after adjustment for differences in patient characteristics (OR 2.1, 95?% CI 1.1–4.3).

Conclusion

Takotsubo cardiomyopathy is currently more often diagnosed in patients with STEMI compared with in earlier years. This is probably due to the increased scientific and clinical awareness among doctors, but the prevalence is still low.

     

Induction of apoptosis in human glioma cell lines of various grades through the ROS-mediated mitochondrial pathway and caspase activation by <Emphasis Type="Italic">Rhaponticum carthamoides</Emphasis> transformed root extract

The placenta plays a major role in embryo-fetal defects and intrauterine growth retardation after maternal alcohol consumption. Our aims were to determine the oxidative status and cellular and molecular oxidative stress effects on uterine myometrium and trophoblast-decidual tissue following perigestational alcohol intake at early organogenesis. CF-1 female mice were administered with 10% alcohol in drinking water for 17 days prior to and up to day 10 of gestation. Control females received ethanol-free water. Treated mice had smaller implantation sites compared to controls (p < 0.05), diminished maternal vascular lumen, and irregular/discontinuous endothelium of decidual vessels. The trophoblast giant cell layer was disorganized and presented increased abnormal nuclear frequency. The myometrium of treated females had reduced nitrite content, increased superoxide dismutase activity, and reduced glutathione (GSH) content (p < 0.05). However, the trophoblast-decidual tissue of treated females had increased nitrite content (p < 0.05), increased GSH level (p < 0.001), increased thiobarbituric acid-reactive substance concentration (p < 0.001), higher 3-nitrotyrosine immunoreaction, and increased apoptotic index (p < 0.05) compared to controls. In summary, perigestational alcohol ingestion at organogenesis induced oxidative stress in the myometrium and trophoblast-decidual tissue, mainly affecting cells and macromolecules of trophoblast and decidual tissues around early organogenesis, in CF-1 mouse, and suggests that oxidative-induced abnormal early placental formation probably leads to risk of prematurity and fetal growth impairment at term.