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.

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 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.

The prevalence of low physical activity in an urban population and its relationship with other cardiovascular risk factors: Findings of a community-based study (KERCADRS) in southeast of Iran.

BACKGROUND: The low physical activity (LPA) more or less affects every community. Because of high prevalence of cardiovascular diseases in Iran and their relationship with LPA, this study aimed to measure precisely the epidemic size of LPA and determine its relationship with six other coronary artery disease (CAD) risk factors among an urban population aged 15 to 75 years in Kerman, Iran. METHODS: Using household survey, 5895 adults were randomly recruited through single-stage cluster sampling from 250 postal codes. Demographic characteristics, blood pressure, blood glucose, cholesterol, triglyceride, smoking, opium use, mental status and physical activities at work, rest and recreation were assessed and ranked as low, moderate and intense. Adjusted odds ratio (AOR) was reported as a measure of the relationship between LPA and other CAD risk factors. RESULTS: The prevalence of low, moderate, and intense physical activity were 42.1% (40.3-43.9), 45.0% (43.6-47.4) and 12.4% (11.1-13.9), respectively. LPA showed a sudden rise from 36.8% to 45.4% after the age of 25 years. On average, women had less physical activity than men (45.1% vs. 39.2%, P= 0.01). Participants with low physical activity compared to those without physical activity had significantly higher chance of anxiety [odds ratio 1.39; confidence interval (95% CI) 1.08-1.79; P = 0.01], hypertension (1.59; 1.08-2.35; P = 0.02), hyper-cholesterolemia (1.37; 1.06-1.76; P = 0.02), cigarette smoking (1.52; 1.07-2.11; P = 0.01), opium addiction (1.47; 1.07-2.02; P = 0.02) and overweight/obesity (1.34; 1.05-1.71; P = 0.02). CONCLUSION: LPA was very common in the studied population and almost half of the adults were at risk for CAD because of insufficient level of physical activity. Such risky life-style pattern makes the emerging of CAD epidemic unavoidable, if effective interventions not being in place timely to this community.

Effects of digoxin on cardiac iron content in rat model of iron overload.

BACKGROUND: Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca2+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood. METHODS: We assessed the effect of different concentrations of digoxin on cardiac iron content in rat model of iron overload. Digoxin had been administrated intraperitoneally (IP) for one week before main study began to assure increased digoxin levels. Group 1 received four IP injections of iron-dextran (12.5mg/100g body weight) every 5 days evenly distributed over 20 days. Groups 2-4 received 0.5, 1 and 5 mg/kg/day IP digoxin, respectively. Last three groups 5-7 received iron-dextran as group 1 and digoxin concentrations 0.5, 1 and 5 mg/kg/day, respectively. RESULTS: Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (0.5, 1 and 5 mg/kg/day) of digoxin than their counterparts in control groups and this pattern was also observed in pathology assessment. CONCLUSION: It seems that digoxin plays an important role in iron transport into heart in iron overload state but exact mechanism of this phenomenon is not clear. L-type Ca2+ channels are good candidates that probably could be involved in iron accumulation in cardiomyocytes. Thus it would be better to reconsider digoxin administration in thalassemia and iron overload conditions.

On the Occasion of World Cancer Day 2015; the Possibility of Cancer Prevention or Treatment with Antioxidants: The Ongoing Cancer Prevention Researches.

On February, 2014 World Cancer Day (WCD) was established to raise alertness of cancer and to encourage its prevention, detection, and treatment. In fact, WCD is celebrated every year on the 4(th) of February all over the world to commemorate all the accomplishments of the WHO. In this paper, we aimed to present the scientific evidence for the role of antioxidants in cancer. Damage to cells by reactive oxygen species, especially the damage to DNA, has been found to play a crucial role in the development of cancer. Exogenous antioxidants can prevent free radical damage associated with cancer development. However, whether or not taking dietary antioxidants can prevent or reduce the risk of developing cancer in humans is not clear. Some researchers have suggested that antioxidants counteract with drugs or toxins, which induce oxidative stress and hence prevent damage to cells or body organs.

Brain and Lung Abscesses in a 48-year-old Man with Focal and Segmental Glomerulosclerosis.

Focal segmental sclerosis (FSGS) is a common cause of idiopathic nephrotic syndrome in the adult population. A patient aged 48- year-old was admitted for evaluation of azotemia. Renal biopsy showed tip lesion FSGS and acute tubular necrosis. After methyl prednisolone pulse therapy, partial remission occurred, and he was stable with oral prednisolone and cyclosporine. Few months later two serious complications including lung and brain abscess occurred. We describe a case of FSGS with lung and brain abscess, who responded to medical management.

Association of glomerular C4d deposition with various demographic data in IgA nephropathy patients; a preliminary study.

BACKGROUND: IgA nephropathy (IgAN) is the most prevalent primary chronic glomerulopathy worldwide. Thus, it is of vital importance to search for factors aggravating the disease progress, monitor disease activity and predict disease-specific therapy. C4d is a well-known biomarker of the complement cascade with a potential to meet the above needs. OBJECTIVES: The aim of our study was, therefore, to determine whether C4d staining at the time of kidney biopsy had any correlation with the demographic, clinical and biochemical variables in IgAN. PATIENTS AND METHODS: The definition of IgAN requires the presence of diffuse and global IgA deposits which were graded ≥2+ and weak C1q deposition. C4d immunohistochemical staining was conducted retrospectively on 29 renal biopsies of patients with IgAN, which were selected randomly from all biopsies. C4d immunohistochemical staining was performed on 3-µm deparaffinized and rehydrated sections of formaldehyde-fixed, paraffin-embedded renal tissues. RESULTS: Of 29 selected patients, 68% were male. In this study, 54.2±25 percent of glomeruli in all biopsies were positive for C4d. The mean and standard deviation (SD) of serum creatinine and the magnitude of proteinuria were 1.72±1.2 mg/dl and 1582±1214 mg/day, respectively. In this study, we observed statistically significant correlations of percent C4d positivity with the serum creatinine (r=0.61, p=0.0005), magnitude of proteinuria (r=0.72, p=0.0001), the proportion of globally sclerotic glomeruli (r=0.43, p=0.02) and the proportion of tubulointerstitial fibrosis (r=0.54, p=0.0023). CONCLUSIONS: The results from our investigation on C4d positivity in biopsy-proven cases of IgAN are in accord with some of the previous studies. These findings, however, require further validation in larger samples.

Adiponectin and chronic kidney disease; a review on recent findings.

Adiponectin is a multifunctional cytokine that has a role in regulating inflammation. In patients without chronic renal failure (CRF) and type 2 diabetics, decreased adiponectin levels are associated with insulin resistance. Lower serum plasma adiponectin values are link to larger tumor size and metastasis in clear-cell carcinoma of the kidney too. However, in patients with established chronic kidney disease (CKD), adiponectin levels are elevated and positively predict progression of disease. In addition, increased levels of serum adiponectin of hemodialysis patients were associated with decrease in bone mineral density in hemodialysis patients. Thus, depending on type of renal failure should be adjusted the adiponectin levels in patients. In CKD patients without diabetic, decreasing adiponectin levels by ARB drugs may be appropriate for inhibition of disease progression.

Massive proteinuria and acute glomerulonephritis picture in a patient with Familial Mediterranean fever and E148Q mutation.

Familial Mediterranean fever (FMF) is an inherited auto-inflammatory disorder. Secondary AA amyloidosis is the most devastating complication of FMF. Nonamyloid renal involvements have also been reported in association with FMF, including vasculitis, focal and diffuse glomerulonephritis, and IgA nephropathy. We describe a patient with FMF and E148Q mutation who presented with massive proteinuria, elevated serum creatinine level, and acute glomerulonephritis picture. Disease remission was achieved after treatment with corticosteroids and colchicine.

A biochemical study on ameliorative effect of green tea (Camellia sinensis) extract against contrast media induced acute kidney injury.

INTRODUCTION: Reactive oxygen species have been shown to be mediators of kidney injury and green tea polyphenols are potent-free radical scavengers. OBJECTIVES: In this study we sought to examine whether green tea was able to protect renal toxicity induced by contrast media or not. MATERIALS AND METHODS: In this experimental study 40 rats were randomly divided into four groups including: 1) control group 2) contrast media group 3) contrast media plus green tea 4) Green tea pretreatment and contrast media group. Blood urea Nitrogen (BUN) and serum creatinine were assessed for severity of kidney injury. RESULTS: Serum creatinine level was higher in group II than in other groups (p<0.001). Treatment (group 3) or pretreatment (group 4) with green tea significantly reduced blood creatinine level when compared with contrast media group (group 2). CONCLUSION: In this study, beneficial property of green tea, against renal toxicity of contrast media was observed. Green tea extract is an inexpensive, nontoxic, and effective treatment modality in individuals with a risk for acute kidney injury of contrast media.

Aggravation of immunoglobulin a nephropathy by hyperuricemia: a mini-review on current findings and new concepts.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common form of primary glomerulopathy worldwide. Various investigations have addressed the clinical and morphological risk factors related to the risk of progression. Recently, much attention has been made toward the prognostic implication of serum uric acid in patients with IgAN. It has been observed that treatment of hyperuricemia with allopurinol in chronic kidney failure has resulted in a fall in blood pressure and inhibition of the progression of kidney injury. Recent studies have documented that hyperuricemia is an independent risk factor for IgAN, and appropriate treatment by allopurinol is a reasonable modality in these patient. We believe that allopurinol should routinely be included to the treatment of IgAN patients; however, this hypothesis requires further investigation. Clinical studies are suggested to better understand kidney protective properties of allopurinol in IgAN.

Hypertension: diagnosis, control status and its predictors in general population aged between 15 and 75 years: a community-based study in southeastern Iran.

OBJECTIVES: Hypertension (HTN) is an important cause of cardiovascular related morbidity and mortality. This study aimed at providing the prevalence of pre-HTN, diagnosed and undiagnosed HTN, along with its control and associated factors in an adult population. METHODS: 5,900 participants aged 15-75 years took part in the study. HTN was verified by examination, self-reported history or using anti-hypertensive drug(s). Pre-hypertension and hypertension were defined as 120-139/80-89 mmHg and >140/>90 mmHg for systolic/diastolic BP, respectively. RESULTS: The prevalence of hypertension was 18.4 % from which 10.5 %were diagnosed and 7.9 % were undiagnosed. The prevalence of pre-HTN was 35.5 %. HTN increased by age (2.4 % in 15-24 to 49 % in 55-64 years). The men had higher pre-HTN (42.7 vs. 28.1 %) and undiagnosed HTN (11.3 vs. 4.6 %). Of those diagnosed, 56.3 % had uncontrolled BP levels. Smoking, anxiety, obesity, and positive family history of HTN were the most significant predictors for HTN. CONCLUSIONS: Hypertension affected almost one-fifth of the population. Given the poor control in diagnosed hypertensive patients, it is alarming that the current health system in urban areas in Iran is not effective enough to control the epidemic spread of non-communicable diseases.

Clinicopathological correlations in lupus nephritis; a single center experience.

BACKGROUND: Renal biopsies play an important role in the diagnosis, management and prognosis of patients with lupus nephritis (LN). OBJECTIVES: To determine the correlation between the pathological features of LN and the demographic, clinical and laboratory parameters. PATIENTS AND METHODS: This retrospective study was conducted from 2008 to 2014 on all consecutive cases of biopsy-proven LN at a nephropathology laboratory in Iran. The demographic, clinical and laboratory data were obtained from patients(') files and the biopsy findings from the original biopsy request forms. RESULTS: Of the 84 patients enrolled, 69 (82.2%) were females and 15 (17.8%) males. The mean age was 32.7±12 years. The mean serum creatinine was 1.5±0.94 mg/dl and the mean 24-h proteinuria, 1.6±1.9 grams. The majority of cases belonged to classes III and IV. The extracapillary proliferation was found in 42.86% of biopsies and endocapillary proliferation in 66.67% of biopsies. Patients of class IV-LN had a higher mean serum value of creatinine in comparison to class III-LN (2.19±1.09 versus 1.2±0.56 mg/dl; p= 0.0001). There was no significant difference of 24-h proteinuria between the two classes (p= 0.882). A significant association of serum creatinine with 24-h proteinuria (p= 0.041) was seen. Serum creatinine had significant positive correlation with activity percent (p< 0.001), and chronicity percent (p= 0.006), and also with proportion of glomeruli with crescents (p < 0.001). While there was a significant relationship of proteinuria with chronicity percent (p= 0.001), this association for activity percent was not significant (p= 0.094). Furthermore, the association of proteinuria with totally sclerotic glomeruli and proportion of crescents was not statistically significant (p= 0.186 and p= 0.0145 respectively). CONCLUSIONS: In conclusion, the results from our study on biopsy-proven cases of LN largely concur with the previously reported studies from Iran and other parts of the world.

Contrast-induced nephropathy; A literature review.

CONTEXT: Contrast-induced nephropathy (CIN) is a common cause of acute kidney dysfunction. EVIDENCE ACQUISITIONS: Directory of Open Access Journals, Google Scholar, PubMed, EBSCO and Web of Science have been searched. RESULTS: It is necessary to identify at risk patients at early stages to implement preventive strategies to decrease the incidence of this nephropathy. However, mechanisms of CIN have not fully explained yet. It seems that mechanisms which mediated by nitric oxide and prostaglandin-induced vasodilatation have been played a crucial role in the CIN. Hemodynamic changes of renal blood flow, which causes hypoxia in the renal medulla and direct toxic effects of contrast media on renal cells, are thought to contribute to the pathogenesis of CIN. Contrast media is normally divided into iso-osmolar, low-osmolar, and high-osmolar. N-acetylcysteine is considered as one of the best choices to prevent CIN in high-risk groups. CONCLUSIONS: The first aim to prevent CIN is identifying high-risk subjects and controlling associate risk factors. As significant differences existed between contrasts agents due to their physicochemical properties, low-osmolar or iso-osmolar contrast media should be used to prevent CIN in at-risk patients. The volume of contrast media should be as low as possible.

New concepts in nutraceuticals as alternative for pharmaceuticals.

Nutraceuticals are products, which other than nutrition are also used as medicine. A nutraceutical product may be defined as a substance, which has physiological benefit or provides protection against chronic disease. Nutraceuticals may be used to improve health, delay the aging process, prevent chronic diseases, increase life expectancy, or support the structure or function of the body. Nowadays, nutraceuticals have received considerable interest due to potential nutritional, safety and therapeutic effects. Recent studies have shown promising results for these compounds in various complications. In the present review much effort has been devoted to present new concepts about nutraceuticals based on their diseases modifying indications. Emphasis has been made to present herbal nutraceuticals effective on hard curative disorders related to oxidative stress including allergy, alzheimer, cardiovascular, cancer, diabetes, eye, immune, inflammatory and Parkinson's diseases as well as obesity. The recently published papers about different aspects of nutraceuticals as alternative for pharmaceuticals were searched using scientific sites such as Medline, PubMed, and Google Scholar. The used terms included nutraceutical and allergy, alzheimer, cardiovascular, cancer, diabetes, eye, immune, inflammatory or Parkinson.