The Association Between Arsenic Levels and Oxidative Stress in Myocardial Infarction: A Case-Control Study.

Cardiovascular diseases (CVDs) are known as the first causes of death throughout the world, and mainly myocardial infarction (MI), lead to 7.4 million deaths annually. Atherosclerosis is the major underlying cause of most CVDs. However, exposure to heavy metals, among other factors, deserves further attention as a risk factor for CVDs. This study was designed to evaluate the levels of arsenic (Ars) in myocardial infarction (MI) patients and healthy individuals as well as assess the association between the incidence of MI and Ars, total antioxidant capacity (TAC), and oxidative stress. This case-control study was conducted among patients with MI (n = 164) and normal individuals (n = 61) at Shafa Hospital in Kerman, Iran. Patients were classified into two groups, including coronary artery blocks above 50% (CAB > 50%, n = 83) and coronary artery blocks less than 50% (CAB < 50%, n = 83) based on their angiography findings. The demographic characteristics, clinical history, biochemical parameters, and serum Ars and TAC levels were evaluated. In the present study, both CAB groups had significantly reduced levels of TAC compared with the control. Furthermore, TAC was lower in the CAB > %50 group compared to the CAB < %50 group. Ars levels were significantly higher in both CAB groups compared with the control. There was a significant positive relationship between CAB and Ars, BG, HbA1c, urea, creatinine, TG, TC, and LDL-c, as well as a negative relationship between HDL-c and TAC. Moreover, TAC levels showed a significant inverse correlation with Ars, HbA1c, and creatinine, and a positive correlation with HDL-c. As risk factors, Ars, hs-CRP, TG, TC, and LDL-c enhance the severity of the disease, and HDL-c and TAC decrease the disease severity. Moreover, ROC curve analysis revealed that the highest AUC for the CAB > %50 (AUC = 78.29), and cytotoxic levels for both CAB groups (Ars ≥ 0.105 ppm), and no significant differences were found between the two groups. Our findings suggest that Ars at ≥ 0.105 ppm is able to increase the risk of MI through the increased OS and decreased TAC.

Association between the FABP2 Ala54Thr and CRP+1059C/G polymorphisms and small dense LDL level in patients with atherosclerosis: a case-control study.

BACKGROUND: The polymorphisms of fatty acid-binding protein 2 (FABP2) and C-reactive protein (CRP) might act as genetic risk factors for atherosclerosis. The study aimed to investigate the relationship between FABP2 Ala54Thr and CRP+1059C/G polymorphisms and atherosclerosis as well as the association of Small dense-LDL (sd-LDL). METHODS: A total of 255 subjects (125 controls and 130 patients) were included. The FABP2 and CRP polymorphisms were determined by PCR-RFLP and AS-PCR methods, respectively. Sd-LDL was measured based on Hirano et al method. RESULTS: There were no significant distinctions between the patient and control groups concerning FABP2 and CRP polymorphisms (p > .05). No significant relationship was observed between studied polymorphisms and sd-LDL level in the patient group (p > .05). However, patients group had higher level of sd-LDL compared to controls (p < .05). CONCLUSION: FABP2 Ala54Thr and CRP+1059G/C polymorphisms were not associated with atherosclerosis and sd-LDL level. However, the increased sd-LDL level was known as a risk factor for atherosclerosis.

Moderate Endurance Training and MitoQ Improve Cardiovascular Function, Oxidative Stress, and Inflammation in Hypertensive Individuals: The Role of miR-21 and miR-222: A Randomized, Double-Blind, Clinical Trial.

OBJECTIVE: Hypertension (HTN) is among the leading causes of myocardial infarction, stroke, and kidney disease. The MitoQ supplement is a mitochondrial-targeted antioxidant that attenuates the generation of reactive oxygen species (ROS). miRNAs play an essential role in the pathophysiology of HTN. Regular aerobic exercise is recommended to decrease the risk of cardiovascular disease. We aimed to evaluate the effects of MitoQ supplementation and moderate endurance training (ET), alone and in combination, on cardiac function, blood pressure, the circulatory levels of miRNA-21 and miRNA-222, and oxidative status in individuals with HTN. MATERIALS AND METHODS: In a double-blind, randomized clinical trial (except for ET group), 52 male hypertensive subjects (40-55 years old) were randomly divided into four groups (n=13): Placebo, MitoQ (20 mg/day, oral), ET (Cycle ergometer, moderate intensity, 40-60% VO2 peak, three sessions/week for six weeks), and MitoQ+ET. Cardiac echocardiography indices, serum oxidative and inflammation status, and miRNAs 21 and 222 were assessed before and after interventions. RESULTS: Left ventricular mass [effect size (ES): -6.3, 95% confidence interval (CI): -11.2 to -1.4] and end-systolic/ diastolic diameters significantly improved in the intervention groups (ES: -0.05, 95% CI: -0.11 to 0.00 and -0.09, 95% CI: -0.16 to -0.02). Total serum antioxidant capacity (TAC) increased (ES: 36.0, 95% CI: 26.1 to 45.8), and malondialdehyde (MDA) (ES: -0.43, 95% CI: -0.53 to -0.32), IL-6 (ES: -1.6, 95% CI: -1.98 to -1.25), miR-21 (ES: -0.48, 95% CI: -0.61 to -0.35), and miR-222 (ES: -0.31, 95% CI: -0.44 to -0.18) significantly decreased in response to ET, MitoQ, and their combination. CONCLUSION: MitoQ and ET, individually and more pronouncedly in combination, can improve cardiovascular health in people with high blood pressure (BP) by reducing inflammation and increasing antioxidant defense, in association with reduction in circulatory miR-21 and miR-222 levels (registration number: IRCT20190228042870N1).

Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals.

OBJECTIVES: Hypertension (HTN) is one of the most important risk factors for cardiovascular diseases. Despite advances in treatment and control of HTN, the prevalence of HTN is still increasing. MitoQ is a supplement that acts on mitochondria and attenuates reactive oxygen species (ROS), which plays an important role in cardiovascular health. miRNAs play an important role in the pathophysiology of HTN. We evaluated the effects of MitoQ supplementation and endurance training (ET), alone and in combination, on functional indices of the heart and serum levels of miR-126, miR-27a, antioxidants, and NO, in patients with HTN. METHODS: In a double-blind randomized clinical trial, 52 male participants (age 40-55 years) were randomly divided into four groups (n = 13) of placebo, MitoQ (20 mg/day, oral), ET (cycle ergometer, moderate intensity, 40-60% VO2 peak, heart rate 120-140 b/min, 45 min a day, three days/week for six weeks), and MitoQ+ET. Cardiac function indices were assessed by echocardiography before and after interventions. RESULTS: Systolic blood pressure (SBP) significantly decreased in all intervention groups (P < 0.001) while DBP (P < 0.01) and LV hypertrophy (P < 0.05) were significantly decreased only in the MitoQ+ET group. Serum levels of SOD, GPx, and NO and the level of miR-126 significantly increased in all treatment groups, while miR-27a reduced in the ET (P < 0.05) and MitoQ+ET (P < 0.01) groups. CONCLUSIONS: Compared to MitoQ and ET alone, their combination has more prominent improving effects on cardiac health and amelioration of BP in the patients with HTN. These effects are through miR-126 and miR-27a modulation and ameliorating mitochondrial ROS production.

Prevalence and incidence of pre-hypertension and hypertension (awareness/control) in Iran: findings from Kerman coronary artery diseases risk factors study 2 (KERCADRS).

Hypertension (HTN) is an important cause of cardiovascular-related morbidity and mortality. The present study was conducted to investigate the prevalence and incidence rate of pre-HTN, diagnosed and undiagnosed HTN, as well as its control and associated factors in adult population in southeast Iran. In a randomized household survey, 9987 participants aged 15-80 years were recruited into the study. HTN was confirmed through examination or using antihypertensive drug(s). Pre-HTN and HTN were defined as 120-139/80-89 and ≥140/90 mmHg for systolic and diastolic BP, respectively. The prevalence of pre-HTN was 28.5%. The prevalence of HTN was 19.2% (13.9% diagnosed and 5.3% undiagnosed). HTN increased with age (from 4% in 15-24 to 67.8% in 75-80 years). Men had higher pre-HTN (35.6% vs. 23.4%) and undiagnosed HTN (7.5% vs. 3.8%) than women. Of those diagnosed, 46.5% had uncontrolled BP, in which, women had better conditions than men (45.6% vs. 47.4%). Obesity, positive family history of HTN, anxiety, and low physical activity were the most significant predictors of HTN. The prevalence of pre-HTN decreased but there was no change in the prevalence of HTN during the last 5 years. The 5-year incidence rate/100 person-years of pre-HTN and HTN was 6.6 and 3.7, respectively. Although there are some promising signs of reducing pre-HTN and slowing HTN rise, currently, almost one-fifth of the adult population suffers from HTN. Given the poor BP control in patients with diagnosed HTN, especially in men, alarms that more effective interventions and strategies are needed to reduce deleterious consequences of HTN.

Effect of Hydroethanolic Extract of Nigella sativa L. on Skin Wound Healing Process in Diabetic Male Rats.

BACKGROUND: The aim of this study was to investigate the effect of hydroethanolic Nigella sativa L. extract on skin wound healing in diabetic male rats. METHODS: This experimental study was conducted on 49 male Wistar rats weighing 220-250 g divided into 7 groups of 7 each: control (nondiabetic untreated), sham (nondiabetic eucerin-treated), nondiabetic phenytoin (1%)-treated, diabetic untreated, and three diabetic groups treated independently with phenytoin 1%, hydroethanolic N. sativa extracts 20% or 40%. Diabetes was induced with 60 mg/kg streptozosin in one administration. After anesthesia, 2 × 1 cm2 wounds were made on the rats' backs and each group was administered with its own respective treatment until the wounds were healed completely. Tissue specimens were prepared for histological examinations. The areas of the wounds were measured every 3 days. The data were analyzed by ANOVA and Tukey's post-hoc test. RESULTS: The mean duration of wound healing was 27 and 24 days for diabetic untreated and diabetic phenytoin-treated groups, respectively. Wounds were healed completely in nondiabetic untreated, sham, and nondiabetic phenytoin-treated groups on days 23, 24, and 21, respectively. The shortest duration of wound healing was seen in diabetic N. sativa extract (40%)-treated group (15 days) followed by diabetic N. sativa (20%)-treated group (18 days). These two groups were found to have the lowest mean wound area during the study with a significant difference from mean wound area in the controls (P < 0.05). CONCLUSIONS: N. sativa extract significantly promoted wound healing in diabetic rats in comparison with control groups. Although the beneficial mechanism of the promotion of wound healing was not specifically studied, it is believed that the anti-inflammatory and antimicrobial properties of N. sativa would contribute to this enhanced wound healing.

The effect of different digoxin concentrations on heart tissue and antioxidant status in iron-overloaded rats.

BACKGROUND: Thalassaemia is a hereditary disorder and has an economic burden on patients and the government. The most prevalent complication in these patients is iron overload which is followed by cardiomyopathy. Digoxin is considered as a treatment against heart failure in thalassaemia. The present study evaluated the effect of two digoxin concentrations on iron content and antioxidative defense in cardiac tissue of iron-overloaded rats. METHODS: The study was conducted on 48 rats which were divided into 6 groups. Group 1 was the control group and did not receive any treatment and group 2 was the iron overload group. In addition groups 3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS) were assessed in cardiac tissues. RESULTS: Co-administration of iron-dextran and digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P < 0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron overload groups. GPX levels significantly reduced in groups 5 and 6 (iron + digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron control group. CONCLUSION: Digoxin remarkably facilitates iron uptake by cardiomyocytes by affecting other channels such as L-type and T-type Ca2+ channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model deteriorated antioxidative parameters and increased iron entry into heart tissue at higher doses. Therefore, in patients with beta thalassaemia major, digoxin must be administered with great care and serum iron and ferritin must be regularly monitored.

Medicinal Plants, Effective Plant Compounds (Compositions) and their Effects on Stomach Cancer.

Medicinal plants have special importance around the world. Further, they have been noticed for nutrition and illness treatment such as preparation of anticancer new drugs. Therefore, a wide range of studies have been done on different plants, and their anticancer effects have been investigated. Nowadays, cancer is the most important factor of death rate in the developed and developing countries. Among them, stomach cancer is one of the most common malignancies around the world. At present, it is recognized as the fourth common cancer and the second factor of death rate due to cancer. So far, there has been wide range of effort for cancer treatment; however, in most cases, the response to the treatment has been very weak and often accompanied improper subsidiary effects. The present problems as a consequence of chemical treatment and radiotherapy and many subsidiary problems created due to their use for patients, and also, the resistance to the current treatment has motivated researchers to apply new medicines with more effect and less toxicity. The secondary metabolisms existent in the plants have an important role in the treatment of several diseases such as cancer. This study was conducted to investigate and collect scientific results for stomach cancer and to clarify the role of medicinal plants and secondary plant compounds on its treatment.

Nephrolithiasis as a common urinary system manifestation of inflammatory bowel diseases; a clinical review and meta-analysis.

CONTEXT: The extra-intestinal manifestations of inflammatory bowel disease (IBD) are common and involve other organs or systems for example; urinary system. EVIDENCE ACQUISITIONS: For this review, we used a variety of sources by searching through Web of Science, PubMed, EMBASE, Scopus and directory of open access journals (DOAJ). RESULTS: Urinary complications may occur in up to 22% of patients and nephrolithiasis or renal/kidney stones have been suggested to be a common manifestation of disease in forms of uric acid, calcium phosphate or calcium oxalate. We performed a meta-analysis on five clinical trials and reported that correlation between IBD and formation of stone in renal system is positive and significant (Fix-effect model; CI: 95%, P <0.001, and randomeffect model; CI: 95%, P = 0.03). CONCLUSIONS: Based on the reports of the clinical trials, calcium oxalate is more prevalent in Crohn's disease (CD) than in ulcerative colitis (UC).

Soy Protein and Chronic Kidney Disease: An Updated Review.

Chronic kidney disease (CKD) is a serious universal problem that is the main risk for several diseases including cardiovascular disease. Dietary factors are important to prevent and control the kidney disease. Some evidence has shown that modifying the amount and the types of dietary protein exert a major effect on renal failure so limiting dietary protein and substituting animal protein with soy protein has suggested. However, there is a lot of controversy about it, especially in human. Thus, this paper will review the clinical trial studies conducted on the effects of soy protein intake on CKD in both animal and human and its effect mechanism.

The effect of vitamin D administration on serum leptin and adiponectin levels in end-stage renal disease patients on hemodialysis with vitamin D deficiency: A placebo-controlled double-blind clinical trial.

BACKGROUND: The prevalence of vitamin D deficiency is higher in end-stage renal disease (ESRD) patients compared to healthy populations. This deficiency could lead to several complications with different mechanisms and might result in reduced survival in patients. Leptin and adiponectin are messenger proteins with endocrine secretion from adipocytes and various effects in cellular mechanisms. The goal of this study was to find the effect of vitamin D administration on serum levels of leptin and adiponectin in ESRD patients. MATERIALS AND METHODS: This double-blind randomized placebo-controlled clinical trial was carried out on 64 ESRD patients on hemodialysis in the Amin and Noor hospitals of Isfahan, Iran. Patients were categorized into two groups, on control and intervention; serum levels of vitamin D, leptin, and adiponectin were measured in both groups before and after the study. The intervention group was treated with vitamin D pearls, while the control group received placebo in the same manner. RESULTS: The mean [standard deviation (SD)] ages of the patients were 62 (21) years and 60 (19) years in the control and treated groups, respectively. CONCLUSION: The change in serum level of vitamin D was statistically significant in the treatment group but not in the control group. The serum level of leptin was reduced in the treatment group, while the serum level of adiponectin increased significantly, but none of these changes were statistically significant in the control group. This study showed that vitamin D administration is associated with an increase in adiponectin and a decrease in leptin level in ESRD patients.

Effect of angiotensin II type 1 receptor blockade on kidney ischemia/reperfusion; a gender-related difference.

BACKGROUND: Renal ischemia/reperfusion (I/R) injury may be related to activity of reninangiotensin system (RAS), which is gender-related. In this study, it was attempted to compare the effect of angiotensin II (Ang II) receptor type 1 (AT1R) blockade; losartan in I/R injury in male and female rats. MATERIALS AND METHODS: Male and female Wistar rats were assigned as sham surgery, control I/R groups treated with vehicle, and case I/R groups treated with losartan (30 mg/kg). Vehicle and losartan were given 2 hours before bilateral kidney ischemia induced by clamping renal arteries for 45 minutes followed by 24 hours of renal reperfusion. RESULTS: The I/R injury significantly increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr), and kidney tissue damage score in both genders. However, losartan decreased these values in female rats significantly (P < 0.05). This was not observed in male rats. CONCLUSION: Losartan protects the kidney from I/R injury in female but not in male rats possibly because of gender-related difference of RAS.

The effect of the various doses of atorvastatin on renal tubular cells; an experimental study.

BACKGROUND: Recent retrospective observational studies suggest that high-potency statin therapy might increase the risk of acute kidney injury, however data on this subject is scares. OBJECTIVES: This study, was designed to investigate the renal tubular cell effect of different doses of atorvastatin to detect the possible aggravation of renal function or morphology of the kidney. MATERIALS AND METHODS: In this experimental study 24 male Wistar rats were designated into 4 equal groups and treated as follows. Control group received phosphate buffer as the vehicle of atorvastatin for 7 days. Groups 1, II and III received atorvastatin at doses of 10, 50 and 150 mg/kg daily for 7 days, then on the day 8, all rats were anesthetized using ketamine and the blood samples were collected for evaluation of creatinine (Cr) and blood urea nitrogen (BUN) levels and then all rats were sacrificed, then the animals' kidneys were dissected out and histopathological studies were performed. RESULTS: Mean (±SD) of scores of injury to renal tubular cells in control group was 4.2 ± 2.2 and in groups I, II and III were 6.44 ± 4.9, 15.4 ± 8.5 and 25.8 ± 12.7 respectively. Group III which received 150 mg/kg/day of atorvastatin had significant renal damage in comparison to control group (P < 0.001). There was no significant difference of renal injury score between control group with groups of I and II. CONCLUSIONS: In the present study we found, atorvastatin with a dose of 150 mg/kg/day for 7 days was nephrotoxic for rats, while lower doses at 10 mg/kg/day or 50 mg/kg/day for 7 days were not accompanied by renal injury. These findings imply further attention to the administration of higher doses of atorvastatin in clinical conditions.

The role of S-methylisothiourea hemisulfate as inducible nitric oxide synthase inhibitor against kidney iron deposition in iron overload rats.

BACKGROUND: Iron dextran is in common use to maintain iron stores. However, it is potentially toxic and may lead to iron deposition (ID) and impair functions of organs. Iron overload can regulate the expression of inducible nitric oxide synthase (iNOS) in some cells that has an important role in tissue destruction. S-methylisothiourea hemisulfate (SMT) is a direct inhibitor of iNOS, and this study was designed to investigate the effect of SMT against kidney ID in iron overload rats. MATERIALS AND METHODS: 24 Wistar rats (male and female) were randomly assigned to two groups. Iron overloading was performed by iron dextran 100 mg/kg/day every other day for 2 weeks. In addition, during the study, groups 1 and 2 received vehicle and SMT (10 mg/kg, ip), respectively. Finally, blood samples were obtained, and the kidneys were prepared for histopathological procedures. RESULTS: SMT significantly reduced the serum levels of creatinine and blood urea nitrogen. However, SMT did not alter the serum levels of iron and nitrite, and the kidney tissue level of nitrite. Co-administration of SMT with iron dextran did not attenuate the ID in the kidney. CONCLUSION: SMT, as a specific iNOS inhibitor, could not protect the kidney from ID while it attenuated the serum levels of kidney function biomarkers.

On the occasion of world kidney day 2016; work together to better protect the kidney.

CONTEXT: World kidney day is a yearly global alertness and education ceremony, held on the second Thursday in March. EVIDENCE ACQUISITION: Directory of open access journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science have been searched. RESULTS: Once again we reached to March 14, the world kidney day of 2016. This is the 10th anniversary of world kidney day, a program of the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF). World kidney day first began in 2006 and the worldwide campaign highlights a specific theme each year. The theme for 2015 was to invite everybody to drink a glass of water and give one, too, to celebrate their kidneys. This is a symbolic action to memorize that kidneys are vital organs and that they might be cared. CONCLUSIONS: It is a manner to make individuals more conscious about their lifestyle choices. In this year, world kidney day will be celebrated on Thursday March 10, 2016. The theme for 2016 will highlight on renal disease and children.

Serum Klotho Levels in Trained Athletes.

BACKGROUND: Klotho is an anti-aging protein that is predominantly secreted by the kidneys. OBJECTIVES: The aim of the study was to measure and compare the circulating Klotho levels in the serum of trained athletes and in healthy, non-athlete controls. MATERIALS AND METHODS: Thirty trained football players were enrolled and their serum Klotho levels were measured the morning after their last evening exercise training. RESULTS: The plasma free Klotho concentration was significantly higher in the athlete group (3.375 ± 1.48 ng/mL) compared to the non-athletes (1.39 ± 0.43 ng/mL) (P < 0.05). Serum levels of cholesterol, triglycerides, calcium, and phosphorus were not significantly different between the two groups. CONCLUSIONS: Regular aerobic exercise could increase plasma Klotho levels, and this could be an explanation for exercise-related anti-aging effects.