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Background Endothelial dysfunction (ED) has a well-known role in promoting vascular inflammation in Behçet disease (BD). α-klotho is involved in regulation of endothelial function, and its reduction has been reported to be associated with ED.  Objective To assess serum α-klotho in patients with BD, compared with healthy control individuals. Methods In a cross-sectional study, 55 patients with BD and 30 age- and sex-matched healthy controls were enrolled, and their serum levels of α-klotho were measured. Results Common clinical symptoms in patients with BD were oral aphthous ulcers, uveitis, and genital ulcers. Median (IQR) serum α-klotho levels in the BD and control groups were 0.30 (0.20–0.70) and 1.00 (0.70–2.52) ng/mL, respectively. The difference was statistically significant (P  = .005). No significant correlation was observed between serum α-klotho and age (r  = 0.194; P  = .14). Serum α-klotho levels in patients with uveitis were significantly lower. Conclusion α-klotho may have a role in the pathogenesis of ED and is a potential biomarker for uveitis in BD. [ABSTRACT FROM AUTHOR]

Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS). Therefore, to maintain their function, skeletal muscles need a high level of anti-oxidants. [ABSTRACT FROM AUTHOR]

Post-transplant ischemic acute kidney injury (AKI), secondary to ischemia reperfusion injury (IRI), is a major problem influencing on the short and long term graft and patient survival. Many molecular and cellular modifications are observed during IRI, for example, tissue damage result production of reactive oxygen species (ROS), cytokines, chemokines, and leukocytes recruitment which are activated by NF-κB (nuclear factor kappa B) signaling pathway. Therefore, inhibiting these processes can significantly protect renal parenchyma from tissue damage. Klotho protein, mainly produced in distal convoluted tubules (DCT), is an anti-senescence protein. There is increasing evidence to confirm a relationship between Klotho levels and renal allograft function. Many studies have also demonstrated that expression of the Klotho gene would be down regulated with IRI, so it will be used as an early biomarker for acute kidney injury after renal transplantation. Other studies suggest that Klotho may have a renoprotective effect for attenuating of kidney injury. In this review, we will discuss pathophysiology of IRI-induced acute kidney injury and its relation with klotho level in renal transplantation procedure. [ABSTRACT FROM AUTHOR]

Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients. Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or pleotropic effects. Depending on their penetrance into the extra-hepatic cells, statins have different effects on mevalonate/isoprenoid pathway. Lipophilic statins diffuse into all cells and hydrophilic ones use a variety of membrane transporters to gain access to cells other than hepatocytes. It has been suggested that the lower accessibility of statins for extra-hepatic tissues may result in the compensatory induction of mevalonate/isoprenoid pathway and so cancer developing. However, most of the population-based studies have demonstrated that statins have no effect on cancer developing, even decrease the risk of different types of cancer. In this review we focus on the cancer developing “potentials” and the anti-cancer “activities” of statins regarding the effects of statins on mevalonate/isoprenoid pathway in the liver and extra-hepatic tissues. [ABSTRACT FROM AUTHOR]

Intra-articular glucocorticoid (GC) injection has been used for more than half a century in the treatment of refractory synovitis in patients with rheumatoid arthritis (RA). There are limited data about the efficacy of intra-articular injection of various preparations of GCs on inflamed joint. The aim of this study was to compare the efficacy and side effects of intra-articular injection of dexamethasone (DEX) and triamcinolone hexacetonide (TH) in the treatment of knee joint arthritis in RA. In a double-blind randomized clinical trial, 70 patients with RA and knee joint arthritis were recruited to the study. Swelled knee joints were injected with 40 mg TH or 8 mg DEX randomly. The primary outcome measures were reduction of knee joint swelling and pain 1 and 3 weeks after joint injection. The secondary outcome measures were relapse of knee arthritis at 2, 4, and 6 months after injection and side effects of intra-articular injection. Difference in the knee circumferences between DEX and TH groups at weeks 1 and 3 was not significant. The average times of pain reduction after injection were 3.4 ± 2.3 and 2.3 ± 1.8 days in TH and DEX, respectively. There were no differences of knee pain between the two groups. Relapse of knee arthritis was occurred in two (6.7 %) and three (9.4 %) patients in the DEX and TH groups, respectively. Intra-articular injection of DEX like TH causes rapid and long-term reduction of knee pain and swelling in patients with RA and is safe. [ABSTRACT FROM AUTHOR]

Introduction: Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress.Materials and Methods: Thirty-two Sprague-Dawley rats were divided into 4 groups to receive 1 mL/kg/d of olive oil as control; 30 mg/kg/d of cyclosporine; 30 mg/kg/d of cyclosporine and 50 mg/kg/d of valsartan; and 50 mg/kg/d of valsartan. After the 6 weeks of administration period, serum levels of klotho and 8-hydroxydeoxyguanosine were measured using an enzyme-linked immunosorbent assay. Serum malondialdehyde level was measured spectrophotometrically.Results: The mean serum level of klotho was significantly lower in the cyclosporine group compared with control and valsartan groups. Klotho level in the valsartan group was significantly higher than those in the other groups. The cyclosporine group was detected to have significantly higher serum 8-hydroxydeoxyguanosine and malondialdehyde levels compared with the other study groups. The levels of klotho were negatively correlated with 8-hydroxydeoxyguanosine and malondialdehyde levels.Conclusions: Administration of valsartan may lead to attenuation of the nephrotoxic side effect of cyclosporine via enhancing klotho and decreasing oxidative stress levels. [ABSTRACT FROM AUTHOR]

Introduction: Nephrotoxicity as a side effect caused by the immunosuppressive drug, cyclosporine-A (CsA), can be a major problem in transplant medicine. Oxidative stress may play an important role in the CsA-induced nephrotoxicity. It has been shown that the antihypertensive drug, valsartan (Val), has also renoprotective effects but, its molecular mechanism is largely unknown. In the present study, it was aimed to evaluate the Val effect in the alleviation of CsA nephrotoxicity via probable renal glutathione peroxidase (GPx) upregulation and oxidative stress decrease. Methods: Thirty-two Sprague-Dawley rats were divided into four groups based on CsA and/or Val administration: group A (Control, 1 mL/kg/day of olive oil as vehicle), group B (CsA, 30 mg/kg/day), group C (CsA+Val, 30+30 mg/kg/day), and group D (Val, 30 mg/kg/day). After the administration period (six weeks), renal GPx expression was evaluated by real-time polymerase chain reaction (PCR). Plasma levels of GPx and 8-Hydroxydeoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) and protein carbonyl groups (PCG) were measured by spectrophotometer. Plasma levels of urea and creatinine were measured by an autoanalyzer. Results: CsA treatment led to the decrease in renal expression and plasma levels of GPx in comparison to other study groups. Rats received CsA were detected to have significantly (p<0.05) higher plasma 8-OHdG, MDA, PCG, urea, and creatinine levels in comparison to other groups. Plasma urea and creatinine levels were negatively correlated with renal GPx expression and positively correlated with the oxidative stress markers. Conclusion: Administration of Val may result in attenuating the nephrotoxic side effect of CsA via probable renal GPx upregulation, and subsequently oxidative stress decrease. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. Trial Registration: Iranian Registry of Clinical Trials [ABSTRACT FROM AUTHOR]

Introduction: There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C?T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C?T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum- maximum) levels of serum Hcy from 11.40 µmol/L (4.40-28.70) to 9.70 (1.60-20.80) µmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion: Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. [ABSTRACT FROM AUTHOR]

Introduction. Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla protein (MGP) are crucial mediators of vascular calcification and are involved in the development of vascular complications in chronic kidney diseases. This study was set out to investigate the relationship between plasma GAS6 levels and MGP in patients with end-stage renal disease on maintenance hemodialysis. Materials and Methods. Forty-six hemodialysis and 46 healthy individuals with normal kidneys were recruited. Plasma GAS6 and MGP concentrations and related biochemical factors were quantified as well as collection of data on clinical characteristics. Results. Plasma GAS6 levels were significantly higher in the hemodialysis patients as compared with the control group (763.52 ± 187.91 pg/mL versus 421.63 ± 189.91 pg/mL, P < .001). Plasma MGP concentration was significantly lower in the hemodialysis patients than the control group (52.35 ± 12.35 ng/ mL versus 6.60 ± 19.54 ng/mL, P < .001). The levels of GAS6 were inversely associated with MGP (r = -0.341, P = .02) in the hemodialysis patients. Conclusions. Increased GAS6 and decreased MGP levels in hemodialysis patients, as mediators of induction or prevention of vascular calcification, and their inverse correlation may suggest that there might be a role in increased calcification process in hemodialysis patients or only as a secondary phenomenon of advanced kidney failure. Their direct role on vascular calcification needs further studies in the future. [ABSTRACT FROM AUTHOR]

Introduction. Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients. Materials and Methods. Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods. Results. Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P = .004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P = .02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P = .04). Conclusions. Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms. [ABSTRACT FROM AUTHOR]

Introduction. Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients. Materials and Methods. Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods. Results. Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P = .004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P = .02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P = .04). Conclusions. Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms. [ABSTRACT FROM AUTHOR]

Calcification and inflammation are among the important cases of exudative age-related macular degeneration (E-ARMD). The aim of the present study was to elucidate if there is any relationship between serum Osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (RANK-ligand) and E-ARMD. In a cross-sectional study, we compared 45 E-ARMD patients with 45 matched controls. Diagnosis was confirmed by fluorescein angiography. Serum samples were analyzed for OPG, RANK-ligand, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG). The levels of OPG and RANK-ligand were measured by ELISA methods. The mean age was 72.0±1 1.5 years in the E-ARMD group and 68.2±8.9 years in the control group (p=0.09). The level of serum OPG was 132.10±75.49 pg/ml in the E-ARMD group and 94.88±61.65 pg/ml in the control subjects. E-ARMD patients had significantly high levels of OPG (p=0.012), as well as significantly high levels of LDL-C and TC (p=0.001 and p=0.005, respectively). We could not find any significant difference in RANK-ligand, HDL-C, or TG between two study groups (p>0.05). To the best of our knowledge, this is the first study investigating the levels of OPG in E-ARMD patients. The present study showed that E-ARMD patients had high levels of serum OPG. It may act as a protective factor for E-ARMD or only as a secondary phenomenon of different processes of E-ARMD. Further prospective studies would be necessary for prognostic and predictive significance of OPG in patients affected by E-ARMD [ABSTRACT FROM AUTHOR]

The study examined the influence of fish oil (FO) supplementation on serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels as indicated by DNA damage markers and total antioxidant capacity (TAC) among male cigarette smokers. This double-blind, placebo-controlled randomized study was conducted among healthy cigarette smokers (n=40) who were part of a larger prospective cohort study. Twenty smokers were randomly selected to receive FO for 3 months (1 g/day), and another 20 smokers received a placebo for 3 months; 8-OHdG and TAC levels were measured in blood samples before and after the intervention. Serum 8-OHdG significantly decreased (p=0.001) and TAC increased (p<0.001) after 3 months of treatment with FO. Between baseline and endline, the difference in 8-OHdG significantly correlated with the difference in TAC among smokers who received FO (r=-0.540, p=0.014). The study provides evidence that FO supplementation can modify decreased antioxidants and increased oxidative DNA damage in cigarette smokers. [ABSTRACT FROM AUTHOR]

The study examined the influence of fish oil (FO) supplementation on serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels as indicated by DNA damage markers and total antioxidant capacity (TAC) among male cigarette smokers. This double-blind, placebo-controlled randomized study was conducted among healthy cigarette smokers (n=40) who were part of a larger prospective cohort study. Twenty smokers were randomly selected to receive FO for 3 months (1 g/day), and another 20 smokers received a placebo for 3 months; 8-OHdG and TAC levels were measured in blood samples before and after the intervention. Serum 8-OHdG significantly decreased (p=0.001) and TAC increased (p<0.001) after 3 months of treatment with FO. Between baseline and endline, the difference in 8-OHdG significantly correlated with the difference in TAC among smokers who received FO (r=-0.540, p=0.014). The study provides evidence that FO supplementation can modify decreased antioxidants and increased oxidative DNA damage in cigarette smokers. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of the present study was to determine the alterations in high-sensitivity C-reactive protein and Tumor Necrosis factor alpha levels in the blood serum of pseudoexfoliation syndrome cases (a disease with similar risk factors as systemic endothelial dysfunction diseases) and to compare the results with healthy individuals. Methods: High-sensitivity C-reactive protein and Tumor Necrosis factor alpha levels were determined in 30 cases with pseudoexfoliation syndrome and in 30 control patients of the same age and sex, by enzyme-linked immunosorbent assay. Results: The levels of high- sensitivity C-reactive protein and Tumor Necrosis factor alpha in the blood serum of patients with pseudoexfoliation syndrome (3.95±0.88 mg/l, 3.32±0.99 pg/ ml, respectively) were significantly higher than in the control group (2.51±0.79mg/l, 0.43±0.15 pg/ml, respectively) p=0.001, p=0.002. Conclusion: The results suggest that increased levels of high-sensitivity C-reactive protein and Tumor Necrosis factor alpha, as markers of inflammation and peripheral endothelial dysfunction in pseudoexfoliation syndrome, may be risk factors for systemic and ocular manifestations of pseudoexfoliation syndrome. [ABSTRACT FROM AUTHOR]

The article discusses a study to evaluate the efficacy of fish oil (FO) supplements high-density cholesterol (HDL-C)and serum paraoxonase (PON) activity among female patients with rheumatoid arthritis (RA). Participants included 90 RA patients. The study concluded that FO supplementation was found to increase HDL-C as well as PON1 levels among women with RA. The need for future studies covering a larger number and range of female RA patients is highlighted.

Abstract: Objective: The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients. Method: Serum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods. Results: In the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p≤0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p=0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p=0.003]. Conclusion: Although our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future. [Copyright &y& Elsevier]

Abstract: Objectives: Tuberculosis remains one of the most common infectious diseases and a leading cause of mortality world wide. There is some evidence for the possible involvement of Mycobacterium tuberculosis in atherosclerosis. We aim to investigate total antioxidant capacity (TAC), red blood cell superoxide dismutase (SOD) activity, whole blood glutathione peroxidase (GPX) activity, low-density lipoprotein (LDL) susceptibility to oxidation, and malondialdehyde (MDA) levels in patients with pulmonary tuberculosis (PTB). Methods: Forty-five males with active PTB (case group) and 45 healthy age-matched males (control group) were enrolled in the study. TAC, SOD and GPX activities were determined by commercial ELISA kits. MDA levels were measured using the thiobarbituric acid method. LDL susceptibility to oxidation was assessed by measuring lag phase duration. Results: TAC, SOD and GPX activities, and lag phase duration in the case group were significantly lower than the control group (p =.002, p =.004, p =.008, and p =.004, respectively; independent), while the MDA levels was higher in case group (p =.024). Conclusions: Our findings suggest a higher susceptibility of LDL to oxidation and higher levels of lipid peroxidation, and therefore, a possible higher risk of atherosclerosis in patients with PTB. [Copyright &y& Elsevier]

Abstract: Objectives: : To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN). Design and methods: : Lovastatin (20mg/day) was administered to 30 people with T2DN for 90days and then withdrawn for 30days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes. Results: : After 90days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p =0.004, 0.002, and <0.001), while after 30days of lovastatin withdrawal, PON1 and ARE activities and LDL-C lag phase had not changed significantly. Conclusion: : Lovastatin therapy improves PON1 and ARE activities, and LDL-C susceptibility to oxidation. Despite withdrawal of lovastatin, PON1 and ARE activities, and LDL-C susceptibility to oxidation remain unchanged in people with T2DN. [Copyright &y& Elsevier]

Abstract: Objective : Soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) to osteoprotegerin ratio is designated as a bone metabolism equation in many rheumatologic disorders and would be modified with fish oil (FO) supplementation. Design and methods : Eighty-three females with rheumatoid arthritis were divided randomly to 40 and 43 patients treated with (1 g/day) or without FO for 3 months accompanied with conventional drugs, respectively. Osteoprotegerin, sRANKL, tumor necrosis factor alpha (TNFα) serum levels were measured before and after treatment. Results : Serum levels of osteoprotegerin increased, although sRANKL, TNFα and sRANKL/osteoprotegerin ratio decreased with FO therapy. A significant positive correlation was observed between sRANKL/osteoprotegerin ratio and TNFα levels (r =0.327, p =0.040) in the FO-treated group. Conclusions : FO could decrease the inflammatory response by lowering of serum TNFα levels and sRANKL/osteoprotegerin ratio. [Copyright &y& Elsevier]

Purpose: The main aim of this study was to evaluate the inhibitory impacts of the aqueous extract of garlic (Ga) on the formation of cataract induced by sodium selenite (Se). Methods: Thirty-two Wistar albino rat pups (4 equal groups: G1, G2, G3, and G4) were treated as follows: G1, subcutaneous (s.c.) and intraperitoneal (i.p.) injection of normal saline (0.3 mL) on postpartum (day 10); G2, i.p. injection of aqueous extract of garlic (1 mL/kg body weight) and s.c. injection of normal saline (0.3 mL) on postpartum (day 10); G3, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of normal saline (0.3 mL) on postpartum (day 10); and G4, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of aqueous extract of garlic (1 mL/kg body weight) on postpartum (day 10). Daily i.p. injections of aqueous extract of garlic (in G2 and G4) and normal saline (in G1 and G3) were continued for 14 days. The development of cataract was assessed over a period of 2 weeks after injection of sodium selenite. For further examination, the rats’ lenses were removed and analyzed for glutathione (GSH), malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX) activities. Results: In G3 (Se-treated group), all rats developed grade 3 cataract in both eyes. However, in G1 (untreated control group), G2 (Ga-treated group), and G4 (Ga–Se-treated group), the lenses in both eyes of all rats remained clear ( P < 0.0001). This clinical finding was associated with higher GSH level and GPX, SOD activities and lower level of MDA in the Se- and Ga-treated group (G4) compared with SS-treated group (G3) rat lenses ( P < 0.003). Conclusions: Intraperitoneal injection of the Ga in rat model appeared to effectively prevent Se-induced cataract, thus such herbal remedy may be considered for treatment of cataract. [ABSTRACT FROM AUTHOR]

In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms. After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E−L−). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively. 8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups ( P < 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment ( P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention ( r = 0.48, P < 0.001; r = 0.35, P = 0.006). The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: : This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-C, apolipoproteins and paraoxonase (PON) activity in stable hemodialysis patients. Design and methods: : 64 hemodialysis patients were treated with ND at a dose of 100 mg/I.M./week for 4 months. HDL-C, Apo-AI, Apo B, concentrations and PON activity were measured before and after 2 and 4 months of treatment as well as 2 months after withdrawing the treatment. Results: : After 4 months of treatment, an elevation in the serum levels of Apo B (P < 0.0001) and a marked decrease in the concentration of HDL-C (P < 0.0001), Apo-AI (P < 0.0001) and PON activity (P < 0.0001) were found. A significant correlation between PON and both Apo-AI (r = 0.270, P < 0.04) and HDL-C (r = 0.455, P < 0.0001) and also between HDL-C and Apo-AI (r = 0.305, P < 0.02) were found. Conclusion: : Results revealed the adverse effects of ND on apolipoprotein levels in our study population. It is possible that ND reduces PON activity mostly by reducing both the HDL-C and Apo-AI levels. [Copyright &y& Elsevier]

Malnutrition, anemia and increased atherosclerosis are the main causes of mortality in hemodialysis patients. Therapies designed to improve the disorders might therefore be expected to improve outcome. The effects of Nandrolone Decanoate (ND), in 64 stable hemodialysis patients, were studied with respect to the following parameters: nutritional status, hematological indexes, lipid profiles including serum levels of lipoprotein(a) [Lp(a)] in terms of differences in apolipoprotein(a) [apo(a)]. The patients were treated with ND at dose of 100 mg/I.M./week for 4 months. After 2 and 4 months of treatment the elevations in the serum levels of albumin (p < 0.0001), creatinine (p < 0.009), hemoglobin (p < 0.03), hematocrit (p < 0.03), cholesterol (p = 0.007) and triglyceride (p < 0.04) were noticed. Marked decrease in the concentration of high-density lipoprotein cholesterol (p = 0.007) and Lp(a) (p < 0.0001) were also found. These effects after 2 months of treatment withdrawal were relatively constant. By dividing patients according to the baseline Lp(a) levels and molecular weight of apo(a) isoform, it was noticed that the decrease in serum Lp(a) was significant in patients with high Lp(a) (> 30 mg/dl) than those of with low Lp(a) (< 30 mg/dl), irrespective of apo(a) molecular weight. It may be suggested that, ND has beneficial effect on nutritional status and treatment of anemia in hemodialysis patients. In spite the adverse effect of ND on lipid profile, it decreases Lp(a) mostly in patients with high serum Lp(a) preferently by the effect on apo(a) gene transcriptional activity. [ABSTRACT FROM AUTHOR]

One of the important factors in the occurrence of acute kidney injury (AKI) among renal transplant patients (RTPs) is ischemia reperfusion injury (IRI). The current study aimed at determining the anti-inflammatory and anti-oxidative effects of melatonin on the complications of IRI and the level of Klotho expression in these patients. A total of 40 renal transplant candidates were randomly assigned into placebo or melatonin group receiving the same dose of 3 mg/day. In order to measure serum melatonin levels, inflammatory and oxidative stress factors, renal function biomarkers, and Klotho gene/protein expression, venous blood samples were taken from patients over two different time points, i e, 24 h before the transplantation and at discharge from hospital. Melatonin was associated with improvement in renal transplantation, since the serum level of neutrophil gelatinase-associated lipocalin, as a renal functional marker, significantly decreased (P <.001). The effect of melatonin as a suppressor of inflammation and oxidative stress was also evident in the melatonin group due to a significant reduction in the serum levels of MDA, CP, 8-OHdG, and TNF-α markers (P <.001). Reduction in serum levels of renal function and oxidative stress/inflammatory markers in the melatonin group indicates that melatonin can inhibit IRI outcomes in RTPs through its anti-oxidant and anti-inflammatory properties. However, these properties do not appear as a result of influence on the level of Klotho gene/protein expression. • Ischemia/reperfusion injury following renal transplantation is one of the most important factors in the incidence and development of AKI. • Ischemia/reperfusion injury via high production of oxidative stress and inflammatory markers can induce AKI. • Administrated melatonin leads to improvement of kidney functional biomarkers and amelioration of oxidative stress and inflammatory markers. [ABSTRACT FROM AUTHOR]

Introduction: Kidney involvement is a hallmark of systemic lupus erythematosus (SLE) and evaluation of its inflammatory response is demanding. It was the aim of the present study to evaluate the levels of CXCL10 and vitamin D in serum samples of cases with active lupus nephritis (LN).Methods: Fifty lupus patients were enrolled in our study, 25 patients had lupus nephritis and 25 patients were without evidence of LN. Thirty-nine healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of vitamin D and CXCL10 were assessed in the studied groups.Results: Serum levels of CXCL10 were significantly elevated (P≤ 0.020), while vitamin D were diminished in SLE group and active LN as compared with healthy controls and SLE patients without nephritis, respectively. CXCL10 correlated with SLE disease activity index (SLEDAI) and renal activity (P < .05), while vitamin D correlated with C3 and anti-dsDNA antibody (P < .05). Based on the receiver operator characteristic (ROC) curve analysis, CXCL10 and vitamin D levels were not better than conventional biomarkers for discriminating LN patients from non-nephritis SLE patients; however, they could differentiate most of SLE cases from healthy individuals with area under the curve (AUC) ≥ 0.703 (P < .05).Conclusion: Results indicated the importance of elevated levels of CXCL10 and deficiency of vitamin D on the pathogenesis of active LN disease. [ABSTRACT FROM AUTHOR]

Introduction. Kidney involvement is a hallmark of systemic lupus erythematosus (SLE) and evaluation of its inflammatory response is demanding. It was the aim of the present study to evaluate the levels of CXCL10 and vitamin D in serum samples of cases with active lupus nephritis (LN). Methods. Fifty lupus patients were enrolled in our study, 25 patients had lupus nephritis and 25 patients were without evidence of LN. Thirty-nine healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of vitamin D and CXCL10 were assessed in the studied groups. Results. Serum levels of CXCL10 were significantly elevated (P≤ 0.020), while vitamin D were diminished in SLE group and active LN as compared with healthy controls and SLE patients without nephritis, respectively. CXCL10 correlated with SLE disease activity index (SLEDAI) and renal activity (P < .05), while vitamin D correlated with C3 and anti-dsDNA antibody (P < .05). Based on the receiver operator characteristic (ROC) curve analysis, CXCL10 and vitamin D levels were not better than conventional biomarkers for discriminating LN patients from non-nephritis SLE patients; however, they could differentiate most of SLE cases from healthy individuals with area under the curve (AUC) ≥ 0.703 (P < .05). Conclusion. Results indicated the importance of elevated levels of CXCL10 and deficiency of vitamin D on the pathogenesis of active LN disease. [ABSTRACT FROM AUTHOR]

Objective: Considering the important role of serum soluble receptor for advanced glycation end product (sRAGE/RAGE)-ligand system in rheumatoid arthritis (RA), this study aimed to evaluate serum sRAGE levels in RA patients compared to healthy subjects and to assess whether there is an association between sRAGE levels and disease characteristics in RA. Methods: In this cross-sectional study, 60 RA patients according to the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum sRAGE level was measured using ELISA kit. Results: The mean ± SD age of patients and controls was 54.86 ± 11.65 and 50.71 ± 3.72 years, respectively). Serum sRAGE level was significantly higher in RA patients (median [25th and 75th percentiles], 1000.3 [792.00, 1486.8]) compared to healthy controls (median [25th and 75th percentiles], 293.25 [220.35, 364.24]) (p<.001). There was significant difference in serum sRAGE level according to the activity of disease (p<.001). There were significant positive correlations between serum sRAGE level with disease activity (r=0.67, p<.001), ESR (r=0.411, p=.001) and CRP (r=0.273, p=.035). There were no significant correlations between serum sRAGE level with demographic characteristics as well as biochemical measurements including serum creatinine, BUN, RF, and Anti-CCP (p>.05). Conclusions: Our study revealed higher serum sRAGE levels in RA patients compared to healthy controls, which correlated positively with disease activity. [ABSTRACT FROM AUTHOR]

Objective: Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. Methods: In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. Results: Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1 pg/ml and 157.7 ± 88.7 pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r = − 0.06, P = 0.632) and SLEDAI (r = − 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. Conclusions: Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Cisplatin is a broadly prescribed anti-tumor agent for the treatment of diverse cancers. Therapy with cisplatin, however, is associated with various adverse effects including nephrotoxicity and ototoxicity. AMP kinase (AMPK), an evolutionarily conserved enzyme, functions as the fundamental regulator of energy homeostasis. While AMPK activation protects normal tissues against cisplatin-induced toxicities, its impact in cancer is context-dependent and there is no single, uniform role for AMPK. On one hand, some report that AMPK activation augments cisplatin-induced apoptosis in cancer, while on the other hand, few reports indicate that AMPK activation rescues cancer cells from the cytotoxicity induced by cisplatin. Here we review the most salient signaling pathways regulated by AMPK with an emphasis on their relation to cisplatin toxicity and yet discuss context-dependent functions of AMPK in cancer. [ABSTRACT FROM AUTHOR]

Abstract Aims There is increasing evidence showing that mild traumatic brain injury (mTBI) is associated with increased depression-related disorders in humans. Recent studies suggest that dietary intake or supplementation of natural flavonoids like hesperidin can be used for therapy of patients with brain injury and depression. However, the exact mechanisms by which hesperidin indicates its neuroprotective effects are not fully understood. The purpose of this study was to explore the influence of hesperidin on depression-related symptoms in a mouse model of mTBI, and that what mechanisms are primarily involved in the antidepressant effects of this bioflavonoid. Main methods Ten days after mTBI-induction, mice received oral hesperidin treatment (50 mg/kg/14 days), then animals were subjected to different depression tests including sucrose preference test, forced swim test, novelty-suppressed feeding test, and tail suspension test. We also measured levels of tumor necrosis factor (TNF)-α, interleukin-(IL)-1β, malondialdehyde (MDA), and brain-derived-neurotrophic-factor (BDNF) in the hippocampus. Key findings Our results show that mTBI induction induced depressive-like behaviors in mice by increasing inflammatory cytokines (IL-1β and TNF-α) and oxidative stress marker (MDA), and reducing BDNF levels in the hippocampus. Interestingly, hesperidin treatment was effective to significantly reduce depression-related symptoms in mTBI-induced mice. In addition, hesperidin decreased the levels of IL-1β, TNF-α and MDA, and increased BDNF levels in the hippocampus. The major strength of our study is that four behavioral tests gave similar results. Significance This study suggests that the antidepressant-like effect of hesperidin may be mediated, at least in part, by decreased neuroinflammation and oxidative damage, and enhanced BDNF production in the hippocampus. [ABSTRACT FROM AUTHOR]

Introduction. Nontraditional risk factors for cardiovascular disease (CVD), including mineral disorder, high fibroblast growth factor 23 (FGF23), low klotho, and low soluble TWEAK could predict the incipient risk of CVD in chronic kidney disease (CKD). The present study evaluates the effect of sevelamer on soluble tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and klotho levels in adenine-induced CKD rats. Methods and Materials. Normal control rats without sevelamer were compared with 3 groups of adenine-induced CKD rats, including CKD rats without sevelamer, CKD rats treated with 3% sevelamer, and rats receiving adenine and 3% sevelamer concurrently. After 4 weeks of sevelamer treatment, serum levels of klotho and soluble TWEAK were measured, along with biochemical parameters related to kidney function. Results. Sevelamer significantly reduced serum levels of phosphate and increased serum levels of klotho and soluble TWEAK. Decreased levels of phosphate were negatively correlated with elevated levels of klotho and soluble TWEAK (r = -0.70, P = .003; r = -0.58, P = .02; respectively) in serum. Conclusions. Sevelamer successfully reduced serum levels of phosphate, and meanwhile, it led to an elevation in serum levels of klotho and soluble TWEAK in rat models of CKD. [ABSTRACT FROM AUTHOR]

Clinical and experimental studies have shown that mild traumatic brain injury (mTBI) is associated with increased anxiety- and depression-related behaviors and inflammation in the brain. Unfortunately, there are no specific therapies for long-term behavioral consequences of mTBI. This study set out to determine whether silymarin treatment compared to diazepam (DZP) and fluoxetine (FLX) can reduce neuroinflammation, anxiety- and depression-like behaviors after mTBI induction in mice. We used open field, elevated plus maze, light-dark box, zero maze, sucrose preference, forced swim, and tail suspension tests to assess anxiety and depression-like behaviors in mTBI-induced mice. The levels of tumor necrosis factor (TNF)-α protein, a marker of inflammation, in the prefrontal cortex and hippocampus was also measured. This study identified that the long-term treatment with DZP, FLX or SIL results in decreased anxiety and depression-like behaviors in mTBI-induced mice. The results also showed that these drugs reduced TNF-α levels in the prefrontal cortex and hippocampus. In addition, there were no significant differences between the effects of SIL and DZP or SIL and FLX on behavioral and cytokine levels in mTBI-induced mice. Our findings support the idea that mTBI could be a risk factor for anxiety- and depression-related disorders and neuroinflammation in the brain. Taken together, this study demonstrates that DZP, FLX or SIL can significantly reduce anxiety- and depression-like symptoms, and neuroinflammation after mTBI induction in mice. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to characterize the status of vitamin D in patients with active and recently diagnosed Behcet's disease ( BD) and the relationship between vitamin D levels and BD activity. Methods and materials In this cross sectional study 48 patients with BD and 47 age- and sex-matched healthy controls were included. BD was diagnosed by the International Criteria for BD. Behcet's patients were new cases who were not on any treatment. BD activity was measured by the Iranian Behcet's Disease Dynamic Activity Measure ( IBDDAM) and Behcet's Disease Current Activity Form ( BDCAF). 25( OH)D measured by enzyme-linked immunosorbent assay method as an indicator of vitamin D status. Results The mean 25-hydroxyvitamin D (25( OH)D level in the BD group was lower than the control group. Insufficiency and deficiency of 25( OH)D in the BD group was more common than the control group. No correlation was observed between the total IBDDAM, ophthalmic IBDDAM, and BDCAF with 25( OH)D levels. No correlation was found between the major symptoms of BD and 25( OH)D value. Conclusions Our study suggests that deficiency of 25( OH)D may be a trigger factor for BD. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients on maintenance hemodialysis (HD) face an increased risk of atherosclerosis, a crucial problem and the leading cause of cardiovascular morbidity and mortality. This study was designed to evaluate the effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients on HD. Methods: This double-blind randomized controlled trial was conducted from June 2005 to June 2007. Sixty HD patients were enrolled and divided into two groups: treatment (case) and control. The treatment and control groups were treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc concentration was measured by atomic absorption spectrophotometry. PON activity was evaluated by spectrophotometric method. Lipid profile was determined using commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were measured by commercial immunoturbidimetric kits. Results: In the case group, there was no significant change in the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly increased ( p = 0.02). In the control group, although significant increases were observed in the serum levels of TC, TG, and Apo-B ( p = 0.009, 0.019, and 0.001, respectively), the serum PON activity was significantly decreased ( p = 0.025) and the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of intervention period, the serum level of Apo-AI and PON activity were significantly higher in the case group. Conclusions: Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients. [ABSTRACT FROM AUTHOR]

Introduction. We aimed to evaluate the high-sensitivity C-reactive protein (HS-CRP) level changes at the beginning and after withdrawal of lovastatin therapy in patients with diabetic nephropathy. Materials and Methods. Thirty male patients with type 2 diabetes mellitus and diabetic nephropathy were enrolled in the study. Lovastatin, 20 mg/d, was administered for 90 days. Afterwards, Lovastatin was withdrawn for the next 30 days. Blood samples were obtained before the intervention, on the 90th day, and days 1, 7, and 30 after withdrawal of Lovastatin. Serum level of HSCRP was determined by enzyme-linked immunosorbent assay. Alterations in lipid profile was assessed, as well, and compared with that of HS-CRP. Results. Serum level of HS-CRP was significantly reduced after 90 days of lovastatin therapy (P < .001). Then, the HS-CRP reached the pretreatment baseline level on the 7th day after lovastatin withdrawal and maintained until the 30th day (P < .001). Serum HS-CRP changes showed no significant association with lipid profile except for serum total cholesterol level (r = 0.9, P = .006) after 3 months of lovastatin therapy. Their association was reevaluated after 7 days and 1 month of treatment withdrawal and no significant correlations were found. Conclusions. Our findings suggest that lovastatin decreases serum CRP level in patients with diabetic nephropathy, and 7 days after lovastatin cessation, CRP level increases again. [ABSTRACT FROM AUTHOR]

Hyperlipidemia and increased degree of oxidative stress are among the important risk factors for Atherosclerosis in renal transplant recipients (RTR). The Medical treatment of hyperlipidemia in RTR because of drugs side effects has been problematic, therefore alternative methods such as using of Garlic as an effective material in cholesterol lowering and inhibition of LDL Oxidation has been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients with stable renal function were selected and divided into 2 groups. They took one clove of garlic (1 gr) by chewing or swallowing for two months, after one month wash-out period, they took garlic by the other route. Results indicated that although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood pressure did not change, Systolic blood pressure decreased from 138.2 to 132.8 mmHg (p=0.001) and Malondialdehyde (MDA) decreased from 2.4 to 1.7 nmol/ml (p=0.009) by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl (p=0.03), triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008), MDA decreased from 2.5 to 1.6 nmol/ml (p=0.001), systolic blood pressure decreased from 137.5 to 129.8 mmHg (p=0.001), diastolic blood pressure decreased from 84.6 to 77.6 mmHg (p=0.001) and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03) by chewing route too. However HDL, LDL and cyclosporine serum levels had no significant differences by both of swallowing and chewing routes. We conclude that undamaged garlic (swallowed) had no lowering effect on lipid level of serum. But Crushed garlic (chewed) reduces cholesterol, triglyceride, MDA and blood pressure. Additionally creatinine reduced without notable decrease in cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating effect of garlic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Klotho, an anti-aging protein, has protective roles against neurological disorders. • Klotho may have anti-seizure effects by mediating different factors and pathways. • Enhancing brain Klotho may be a possible therapeutic approach to relieve seizures. • Klotho gene has potential to be a therapeutic target for seizure-related disorders. Recurrent seizures in epilepsy may lead to progressive neuronal damage, which can diminish health-related quality of life. Evaluation and control of pathological processes in the brain is valuable. It seems imperative that new markers and approaches for seizure alleviation be discovered. Klotho (Kl), an antiaging protein, has protective effects in the brain against neurological disorders. It may also have antiseizure effects by improving creatine transfer to the brain, upregulating excitatory amino acid transporters, and inhibiting insulin/insulin-like growth factor-1 (IGF-1), Wingless (Wnt), transforming growth factor-beta (TGF-β), and retinoic-acid-inducible gene-I (RIG-I)/nuclear translocation of nuclear factor-κB (NF-κB) pathways. Stimulation and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and apoptosis signal-regulating kinase 1 (ASK1)/p38 mitogen‑activated protein kinase (MAPK) signaling pathways could also be considered other possible antiseizure mechanisms of Kl. In the present review, the roles of Kl in the central nervous system as well as its possible anti-seizure properties are discussed for the first time. [ABSTRACT FROM AUTHOR]

Objective: Behcet's disease (BD) is a chronic inflammatory disorder characterized by recurrent oral and genital aphthous ulcers, uveitis and skin lesions. Oxidative stress and inflammation have important role in the pathogenesis of BD. The aim of this study was to assess the effect of Nigella sativa (NS) oil administration on malondialdehyde (MDA), total anti-oxidant capacity (TAC), tumor necrosis factor-α (TNF-α), IL-10 and high sensitivity C-reactive protein (hs- CRP) levels in patients with BD. Materials and Methods: In this randomized, double-blind and placebo-controlled clinical trial, 96 BD patients were randomly assigned to NS or placebo groups. Study groups received 1000 mg/day NS oil and placebo soft gels for 8 weeks. Serum levels of TNF-α, IL-10, hs-CRP, MDA and TAC were measured before and after treatment. Results: Eighty-nine individuals completed the study. Significant decreases in the serum levels of MDA and increases in the serum levels of TAC were found in the NS group. However, differences in the changes of MDA and TAC in the NS and placebo groups were not significant. Pre- and post-intervention changes of TNF-α, IL-10 and hs-CRP levels in the NS group were non-significant. Conclusion: NS 1000 mg per day is probably not effective in reducing the inflammatory and oxidative markers in BD. [ABSTRACT FROM AUTHOR]

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats. Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined. Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury. Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study aimed to follow up patients with polymyositis (PM) and/or dermatomyositis (DM) to determine survival rate, pattern of disease, response to treatment, malignancy incidence and poor prognostic factors (PPFs). Method: A total of 76 patients with PM (n = 47) and/or DM (n = 29) based on Bohan and Peter diagnostic criteria referred to the Imam‐Reza Hospital were followed up from 2004 to 2016. The follow‐up period was considered from diagnosis to patient′s death or last visit. All patients underwent physical examinations and data including age, sex, disease duration, disease subtype, pattern of disease, PPFs and malignancy incidence were collected. Results: Mean age at diagnosis was 45.49 ± 10.88 years and women were predominant (84.2%). Course of disease in the majority of patients (52.6%) was polyphasic, followed by monophasic (31.6%) and chronic‐progressive (5.3%). The 1‐, 5‐ and 10‐year survival rates were 96%, 93% and 92%, respectively. Delay in treatment and dysphagia were common PPFs in the present study. The majority of patients responded to treatment (88.2%) and there were significant differences in cancer and dysphagia between responders and non‐responders to treatment (P < 0.05). The most common cause of death was cancer in four of eight deaths. There was significant difference in survival rates between patients with and without pulmonary involvement (P = 0.001). Moreover, the survival rates were significantly lower in patients with malignancy (P = 0.001). Conclusion: Presence of dysphagia and cancer were associated with poor response to treatment. Pulmonary involvement and cancer incidence significantly affect survival rate. Furthermore, since cancer is the most common cause of death, so this study emphasizes the importance of careful cancer screening in these patients. [ABSTRACT FROM AUTHOR]

Introduction. Diabetic Nephropathy (DN) is one of the main complications of diabetes mellitus, mostly ending to end-stage renal disease. Leptin and C-reactive protein (CRP), as inflammatory markers implicated in the progression of DN, increase in diabetes mellitus, while transferrin and albumin, as members of anti-oxidant defense mechanism, are found to decline. Materials and Methods. In a controlled clinical trial, 65 patients with type 2 DN were assigned to receive lovastatin or placebo, for 3 months, to assess statins' impact on serum levels of leptin, CRP, transferrin, albumin, and lipid profile. Results. Serum levels of CRP (3.52 +/- 4.16 mg/dL to 2.84 +/- 3.06 mg/dL, P = .02), leptin (10.78 +/- 8.30 mg/dL to 7.80 +/- 5.41 mg/dL, P = .006), low-density lipoprotein cholesterol (116.16 +/- 46.54 mg/dL to 85.46 +/- 29.22 mg/dL, P = .001), and total cholesterol (199.00 +/- 43.33 mg/dL to 164.67 +/- 35.19 mg/dL, P = .001) were lowered after lovastatin therapy. Mean serum level of high-density lipoprotein cholesterol increased (40.00 mg/dL to 42.80 mg/dL, P = .005) after the treatment. Lovastatin had no significant effect on albumin and transferrin. Placebo did not change any of the parameters after 3 months. Conclusions. The effect of statins on the inflammatory markers involved in the development of DN is a new approach to evidence supporting the pleiotropic effect of this drug group. [ABSTRACT FROM AUTHOR]

Introduction. Diabetic Nephropathy (DN) is one of the main complications of diabetes mellitus, mostly ending to end-stage renal disease. Leptin and C-reactive protein (CRP), as inflammatory markers implicated in the progression of DN, increase in diabetes mellitus, while transferrin and albumin, as members of anti-oxidant defense mechanism, are found to decline. Materials and Methods. In a controlled clinical trial, 65 patients with type 2 DN were assigned to receive lovastatin or placebo, for 3 months, to assess statins' impact on serum levels of leptin, CRP, transferrin, albumin, and lipid profile. Results. Serum levels of CRP (3.52 ± 4.16 mg/dL to 2.84 ± 3.06 mg/dL, P = .02), leptin (10.78 ± 8.30 mg/dL to 7.80 ± 5.41 mg/ dL, P = .006), low-density lipoprotein cholesterol (116.16 ± 46.54 mg/dL to 85.46 ± 29.22 mg/dL, P < .001), and total cholesterol (199.00 ± 43.33 mg/dL to 164.67 ± 35.19 mg/dL, P < .001) were lowered after lovastatin therapy. Mean serum level of high-density lipoprotein cholesterol increased (40.00 mg/dL to 42.80 mg/dL, P = .005) after the treatment. Lovastatin had no significant effect on albumin and transferrin. Placebo did not change any of the parameters after 3 months. Conclusions. The effect of statins on the inflammatory markers involved in the development of DN is a new approach to evidence supporting the pleiotropic effect of this drug group. [ABSTRACT FROM AUTHOR]

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (−10.68±26.76 mg/dL, P=.015), LDL cholesterol (−9.66±23.92 mg/dL, P=.014), and Ox-LDL (−5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals. [ABSTRACT FROM AUTHOR]