Serum Nitric Oxide Concentration Research Articles

IL-1<i>β</i>, TNF-<i>α </i>and <i>Sambucus nigra</i> Reactive Serum Proteins as Biomarkers of Mild Cognitive Impairment and Alzheimer Disease Progression

Amyloid-β (Aβ) can induce a chronic inflammatory immune response that is associated, amongst many others, to abnormal glycosylation, inducible nitric oxide synthase (iNOS) and nitric oxide (NO). The relation between development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease progression and these serum markers has not been evaluated. Serum levels of iNOs, NO, TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 are determined with commercially available kits. Sialylation of albumin-free serum patterns is determined by Western blot analysis with Sambucus nigra (specific for sialic acid attached to terminal galactose in α2,6 linkage) lectin. Apolipoprotein E (ApoE) haplotype is determined by Western blot using specific anti-ApoE 2, 3 or 4 antibodies. A mini-mental state examination (MMSE) test is also performed in the 10 MCI patients, 19 Alzheimer’s disease (AD) patients and 46 healthy age-matched controls evaluated. The results show an increase of iNOS in MCI and AD but significantly higher NO concentrations are only found in MCI patients. TNF-α and IL-1β concentrations are the only significantly increased cytokines in MCI patients; no differences between control and MCI or AD patients are found in regard to the other cytokines. An abnormal MMSE test result only correlates with a decrease in serum NO concentration in MCI patients. The terminal sialic acid linkage pattern of serum proteins also shows highly significant differences between MCI and AD patient. ApoE3/4 or 4/4 haplotypes are characteristic of MCI and AD patients. Our results imply that increased serum TNF-α, IL-1β, iNOS, NO and alterations of serum proteins glycosylation patterns in adult individuals with an abnormal MMSE test may serve as an early biomarker of MCI and AD development.

Influence of Zhuang medicineBlumea megacephalaextract on gastrointestinal movement and serum nitric oxide concentrations in mice

Influence of Zhuang medicine<i>Blumea megacephala</i>extract on gastrointestinal movement and serum nitric oxide concentrations in mice

Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats.

Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE) and its possible mechanisms in spontaneously hypertensive rats (SHR rats). Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats) were used in this study. Rats were, respectively, given EFE (EFE group), captopril (captopril group), or phosphate-buffered saline (PBS) (normal control group and SHR group) for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II), aldosterone (Ald), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) in plasma were determined by radioimmunoassay, and serum nitric oxide (NO) concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL). After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity.

Comparative evaluation of the aphrodisiac efficacy of sildenafil and Carpolobia lutea root extract in male rabbits.

Aims:In spite of the folkloric use of the root of Carpolobia lutea as a sexual stimulant in man, there has been limited scientific proof of its efficacy. This study compares the efficacy of methanol extract of C. lutea root (MECLR) and sildenafil on the sexual activity of male rabbits.Methods:20 adult male rabbits were grouped into four of five rabbits each. Groups 1-4 were treated orally for 28 days with 2 ml/kg 1% Tween-20 (vehicle), 40 mg/kg MECLR, 80 mg/kg MECLR, and 0.5 mg/kg sildenafil citrate (SC), respectively. Sexual activities of males from each group were assessed by cohabiting them with sexually receptive female at estrus on days 0, 1, 3, and 5 using digital camera mounted on mating arena. Serum testosterone and nitric oxide concentration of the corpora cavernosa homogenates were also determined.Results:MECLR caused a dose-dependent significant increase in mount frequency, intromission frequency and ejaculatory latency (EL) while it reduced mount latency, intromission latency and post EL (similar to SC) when compared with the control. MECLR also caused significant increase in nitric oxide concentration in corpora cavernosa but no change in serum testosterone concentration.Conclusions:Results suggest that MECLR enhances male sexual activity possibly by augmenting nitric oxide concentration. This study thus provides a novel scientific rationale for the use of C. lutea in the management of penile erectile dysfunction and impaired libido.

Effect of some Neuroprotective drugs on certain biochemical parameters during experimental brain ischaemia.

Cerebral ischaemia reperfusion (I/R) triggers a complex series of biochemical events that lead to formation of reactive oxygen species (ROS) and the impairment of enzymatic mechanisms, which result in tissue oxidative stress. This study investigated the effect of some neuroprotective drugs such as vinpocetine, cinnarizine, pyritinol, and rosiglitazone on oxidative stress and cell death biomarkers occurred during experimental brain ischemia/reperfusion injury in rats. Adult male albino Wistar rats were subjected to 1 hr of brain ischaemia followed by reperfusion for 2 hr. Rats were orally treated with aqueous suspension of vinpocetine (3 mg/kg), cinnarizine (7 mg/kg), pyritinol (55 mg/kg), and rosiglitazone (0.5 mg/kg), after 1 hr of ischaemia. Brain superoxide dismutase (SOD), glutathione (GSH), and malondialdhyde (MDA) contents and serum nitric oxide (NO), lactate dehydrogenase (LDH), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH) levels were quantified at the end of the experiment. I/R injury caused a significant decrease in the activity of brain SOD, GSH contents and serum CAT level. It caused a significant increase in serum NO, LDH, G6PDH levels, and brain MDA content in comparison with the sham-operated group. Vinpocetine and rosiglitazone reversed all these biochemical indices. Pyritinol reversed all these biochemical indices except serum NO, and G6PDH. Cinnarizine could not affect brain MDA, serum NO and CAT levels. Both vinpocetine and rosiglitazone may be potent neuroprotective agents against experimental brain I/R injury in rats. Cinnarzine and pyritinol showed a marked neuroprotective activity but less than both drugs.

Abstract 11599: Plasma Amino Acid Profiling Identifies Specific Amino Acid Correlations With Cardiovascular Function in Patients With Systolic Heart Failure: Highlighting the Cardio-Hepatic-Skeletal Muscle Axis

Background: The heart has close interactions with other organs’ functions and concomitant systemic factors such as oxidative stress, nitric oxide (NO), inflammation, and nutrition in systolic heart failure (HF). Recently, plasma amino acid (AA) profiling as systemic metabolic indicator has attracted considerable attention in predicting the future risk of human cardiometabolic diseases, but it has been scarcely studied in HF. Methods: Thirty-eight stable but symptomatic patients with left ventricular ejection fraction (LVEF) &lt;45% and 33 asymptomatic individuals with normal brain natriuretic peptide (BNP) value were registered as the HF and control groups, respectively. We analyzed fasting plasma concentrations of 41 AAs using high-performance liquid chromatography, serum NO metabolite concentration, hydroperoxide and high-sensitivity C-reactive protein measurements, echocardiography, and flow-mediated dilatation. Univariate and stepwise multivariate analyses including potential confounders were subsequently performed in the HF group. Results: (1) In the HF group, 17 AAs and two ratios significantly changed compared with those in the control group. (2) Univariate and multivariate analyses revealed that Fischer ratio and five specific AAs, ie, monoethanolamine, methionine, tyrosine, 1-methylhistidine, and histidine have significant correlation with BNP value, LVEF, LV end-diastolic volume index, inferior vena cava diameter, mitral E/e’, and BNP value, respectively (p&lt;0.05). (3) Unexpectedly, further exploratory factor analysis categorized these AAs into hepatic-related (monoethanolamine, tyrosine, and Fischer ratio) and skeletal muscle-related (histidine, methionine, and 1-methylhistidine) factors. (4) Some categorized AAs showed unique correlations with concomitant systemic factors: monoethanolamine, tyrosine, and Fischer ratio with serum NO concentration (p&lt;0.05); histidine with serum albumin (p = 0.0001); and 1-methylhistidine with flow-mediated dilatation (p&lt;0.05). Conclusions: Plasma AA profiling identified correlations of specific AAs with cardiac function and concomitant systemic factors and highlighted the cardio-hepatic-skeletal muscle axis in patients with systolic HF.

Serum nitric oxide and pediatric sepsis outcomes

Background Sepsis is the complex pathophysiologic responsesof the host against systemic infection. Sepsis can cause severeconditions such as septic shock and multiple organ failure.Although we have a better understanding of the molecular basisof sepsis as well as aggressive therapy, the mortality rate remainshigh, between 20-80%. Nitric oxide (NO) is one of the mediatorsassociated with cardiovascular failure, apoptosis and organdysfunction in sepsis.Objective To evaluate for a possible correlation between NOlevels and outcomes in pediatric sepsis.Methods A prospective cohort study was conducted at thepediatric intensive care unit (PICU) of Prof. Dr. R.D. KandouGeneral Hospital in Manado, from June to November 2012. Fortychildren aged one month to five year old, fulfilled the InternationalPediatrics Sepsis Consensus Conference 2 005 criteria were recruited.Nitrite oxide metabolites (nitrite and nitrate) levels were measuredusing a calorimetric assay kit (Cayman®, Catalog No.780001)from venous blood specimens collected at admission. All patientsreceived antibiotics empirically within an hour of the diagnosis.Outcomes of patients recorded were survivor or died, and lengthof stay in PICU.Results Mann-Whitney U test revealed a significant differencebetween median serum NO levels ins urvivors and those who died(18.60 vs. 36.50 fLM/L, respectively; P= 0.016).Conclusion Serum NO concentration is higher in those whodied than in survivors of pediatric sepsis. Specific NO inhibitionmay be beneficial in decreasing morbidity and mortality in thiscondition.

Menopause status as the main factor explaining the gender differences of serum nitric oxide concentrations in middle-aged population.

The aim of this study was to investigate whether the observed differences between serum NOx levels of men and women were influenced by the menopausal status of women. A total of 1,209 eligible subjects, aged 40-60 years, were recruited from among participants of the Tehran lipid and glucose study, and subdivided into three groups: men (n = 457), women with regular cycles (n = 288) and postmenopausal women (n = 464). Serum concentrations of NOx were compared between these groups using Kruskal Wallis-Mann-Whitney U test, followed by Bonferroni correction. ANCOVA was applied for comparison of log-transformed NOx values between groups after adjustment for confounder variables. The mean (SD) of age and BMI did not differ between studied groups. There were statistically significant differences between the medians (inter-quartile ranges) of serum NOx levels in men, women with regular cycles and the postmenopausal women [26 (20-37), 25.5 (19-39) and 29 (21-43) μmol/L], respectively (P = 0.012). Post hoc pair-wised comparison, adjusted with Bonferroni correction, demonstrated that women with postmenopausal status had higher serum levels of NOx values than those women with regular cycle or men (P = 0.011). The results remained unchanged after further adjustment for potential confounders. These results provide evidence that differences observed between serum NOx values of middle-aged women and men are more related to menopausal status rather than gender.

THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE.

The generation of reactive nitrogen/oxygen species (RN/OS) represents an important mechanism in erythropoietin (EPO) expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient). It significantly increased serum concentrations of nitric oxide (NO), hydrogen peroxide (H2O2) and pro-oxidative products such as 8-isoprostanes (8-iso), lipid peroxides (LPO) and protein carbonyls (PC). α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise) resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r = 0.718, P < 0.01). Serum total creatine kinase (CK) activity, as a marker of muscle damage, reached a peak at 24 h after exercise (placebo 732 ± 207 IU · L-1, α-lipoic acid 481 ± 103 IU · L-1), and correlated with EPO (r = 0.478, P < 0.01) in the α-lipoic acid group. In conclusion, the intake of high α-lipoic acid modulates RN/OS generation, enhances EPO release and reduces muscle damage after running eccentric exercise.

Serum nitric oxide and pediatric sepsis outcomes

Background Sepsis is the complex pathophysiologic responsesof the host against systemic infection. Sepsis can cause severeconditions such as septic shock and multiple organ failure.Although we have a better understanding of the molecular basisof sepsis as well as aggressive therapy, the mortality rate remainshigh, between 20-80%. Nitric oxide (NO) is one of the mediatorsassociated with cardiovascular failure, apoptosis and organdysfunction in sepsis.Objective To evaluate for a possible correlation between NOlevels and outcomes in pediatric sepsis.Methods A prospective cohort study was conducted at thepediatric intensive care unit (PICU) of Prof. Dr. R.D. KandouGeneral Hospital in Manado, from June to November 2012. Fortychildren aged one month to five year old, fulfilled the InternationalPediatrics Sepsis Consensus Conference 2 005 criteria were recruited.Nitrite oxide metabolites (nitrite and nitrate) levels were measuredusing a calorimetric assay kit (Cayman®, Catalog No.780001)from venous blood specimens collected at admission. All patientsreceived antibiotics empirically within an hour of the diagnosis.Outcomes of patients recorded were survivor or died, and lengthof stay in PICU.Results Mann-Whitney U test revealed a significant differencebetween median serum NO levels ins urvivors and those who died(18.60 vs. 36.50 fLM/L, respectively; P= 0.016).Conclusion Serum NO concentration is higher in those whodied than in survivors of pediatric sepsis. Specific NO inhibitionmay be beneficial in decreasing morbidity and mortality in thiscondition.

Effect of matrine on NO and ADMA metabolism pathways in serum and tissues of mice with lipopolysaccharide-induced intestine tissue inflammation

To discuss the effect of matrine on nitric oxide (NO) and asymmetric methylarginine (ADMA) metabolism pathways in serum and tissues of mice with lipopolysaccharide (LPS) -induced intestine tissue inflammation. Kunming mice were randomly divided into five groups: the normal control group, the LPS group and matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups. The mice were intragastrically administered with drugs for 3 d (distilled water of the same volume for the normal control group and the LPS group). One hour after the last intragastrical administration, normal saline or LPS (1 mg x kg(-1)) were intraperitoneally injected. Twelve hours later, serum and tissues were collected to determine NO and ADMA levels and observe the pathological changes of intestinal tissues. The Western blot method was adopted to detect the protein expressions of arginine methyltransferases 1 (PRMT1) and dimethylarginine dimethylaminohydrolase 2 (DDAH2) in intestinal tissues. Compared with the model group, matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups showed lower NO content in serum and tissues, higher ADMA level in serum and increased PRMT1 expression in intestinal tissues, but without effect on DDAH2 expression. Matrine could inhibit LPS-induced intestine tissue inflammation in mice. Its action mechanism is related to the decreased NO content in serum and tissues and increased ADMA level in serum and PRMT1 expression in intestinal tissues.

Ethanol extracts of centella asiatica leaf improves memory performance in rats after chronic stress via reducing nitric oxide and increasing Brain-Derived Neurotrophic Factor (BDNF) Concentration

Abstract- Background: Centella asiatica is herbaceous plant that has medicinal value to improve learning and memory. Brain- derived neurotrophic factor (BDNF) has a significant role in memory formation process, while oxidative stress causes memory impairment. Objective: This study aimed to investigate the effects of ethanol extracts of Centella asiatica leaf on memory performance and serum BDNF (neurotrophins) and Nitric Oxide(NO) concentration of rats following chronic electrical stress. Materials and Methods : Twenty male rats (Sprague Dawley) were divided into four groups: control/aquadest group and groups treated with three different doses (mg/kg) of Centella asiatica :150 (CeA150), 300 (CeA300) and 600 (CeA600). Memory performance was tested using probe test in Morris Water Maze before and after oral administration of ethanol extracts of Centella asiatica leaf followed by electrical stress for 28 days. At the last day of memory exercise following chronic stress, blood sample was taken from periorbital veins of all rats. Concentration of serum BDNF and total NO was assessed using ELISA. Data were analyzed using one way ANOVA. Results: Treatment groups had higher percentage in probe test water maze and serum BDNF concentration after chronic stress. Mean time percentage (%) of probe test in water maze performance for control group, CeA150, CeA300, and CeA600 were 53.33±2.43, 55.78±4.16, 63.33±4.07, and 73.55±3.29 (p<0.05). Mean concentration of serum BDNF (ng/ml) for control group, CeA150, CeA300, and CeA600 were 1.52±0.89, 1.49±0.20, 1.73±0.15, and 2.16±0.20 (p<0.05 vs control group). Control group had higher serum NO concentration compared to all treatments groups. Mean concentration of serum NO (μmol/L) for control group, CeA150, CeA300, and CeA600 were 5.94±0.52, 3.98±0.35, 3.06±0.33, and 2.82±0.21 (p<0.05). Conclusion: Ethanol extracts of Centella asiatica leaf increases memory performance and serum BDNF concentration, and also decreases Nitric Oxide levels in rats after chronic stress.

The effect of dietary L-arginine intake on the level of antibody titer, the relative organ weight and colon motility in broilers.

This study was carried out to determine the effect of L-arginine (L-Arg) levels in diet at the starter, grower and finisher phases on immune response, organ development, nitric oxide (NO) metabolism and colon motility in broilers. A total of 500 one-day-old Ross-308 broiler chickens of mixed sex were separated into one Arg-deficient group and four experimental groups. Each group was then divided into five subgroups of 20 birds each. Arginine deficient group for all phases was fed a basal diet which contained 10% less L-Arg than optimum Arg requirement recommended by the breeder. Experimental groups were fed a basal diet supplemented with L-Arg which was progressively 10% increased in groups. Thus, the diet contained 90, 100, 110, 120 and 130% of optimum Arg requirement for each phases in groups, respectively. The highest serum infectious bursal disease antibody titer (IBD) was observed in the experimental group which was fed the diet containing 110% L-Arg at grower phase (P < 0.05), whereas Newcastle disease antibody titer did not differ between groups. The relative weight of spleen increased in groups which were fed the diet containing 120 and 130% L-Arg at starter phase as compared to Arg-deficient group (P < 0.05). The group which was fed the diet containing 110% L-Arg showed highest relative weight of bursa Fabricii at grower (P < 0.05) and finisher (P < 0.01) phases. It was observed that serum nitric oxide (NO) concentration decreased in Arg-deficient group (P < 0.05). The amplitude of spontaneous colon contractility did not differ between groups at the end of all three phases. However, the frequency of spontaneous colon contractility in the Arg deficient group was higher at starter (P<0.05), grower (P < 0.01) and finisher (P < 0.05) phases. These results suggest that the supplementation of L-Arg at higher level than optimum Arg requirement in broiler diet has minimal effect on parameters investigated in the study. However, L-Arg-deficiency may negatively affect immune response and the motility of gastrointestinal system due to disruption of NO metabolism at three phases.

Biomarkers of Cardiovascular Remodeling in Patients on Peritoneal Dialysis

Objectives: The purpose of this study was to determine endothelin (ET)-1 and nitric oxide (NO) serum concentration levels at baseline and after 1 year of peritoneal dialysis (PD) treatment. A further aim was to evaluate the association between ET-1 and NO with parameters of echocardiography and the common carotid artery (CCA) ultrasound, and to assess their impact on cardiovascular remodeling. We also aimed to evaluate the influence of dialysis adequacy and residual renal function (RRF) on cardiovascular remodeling. Methods: This study included 40 PD patients in whom we measured serum ET-1 and NO concentrations, echocardiography and CCA ultrasound parameters. Results: ET-1 decreased and NO serum concentration levels increased (p < 0.01) after 12 months of PD treatment compared to baseline values. Left ventricular (LV) hypertrophy was observed in 77.5% of patients at baseline with significant reduction in LV mass index (LVMI), CCA intima media thickness (IMT) and plaque score after 12 months of PD treatment (p < 0.001). The dialysis adequacy and RRF were significantly associated with LVMI and CCA IMT after 12 months on PD. Conclusion: In our study, ET-1 significantly decreased while NO increased during PD treatment and both were independently related to the cardiovascular remodeling parameters in PD patients.

The association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide concentration with microalbuminuria in patients with gestational diabetes

Gestational diabetes mellitus (GDM) is a glucose intolerant condition that affects 14% of all pregnancies. Diabetes mellitus (DM) occurs in 30 - 70% of patients with GDM after delivery. DM and GDM are associated with structural and functional deterioration of the renovascular system. Our aim is to investigate the association Glu- 298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene with serum nitric oxide levels and microalbuminuria in patients with GDM and healthy pregnancies. Serum nitric oxide (NO) levels, urinary excretion of albumin and Glu298Asp polymorphism of the eNOS gene were analyzed in 68 patients with GDM and 73 healthy controls. High performance liquid chromatography (HPLC-Griess) method was used to analyze serum NO levels. Microalbuminuria was evaluated by rate nephelometry method. The Glu298Asp polymorphism of the eNOS gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Nitric oxide, glucose, creatinine, and microalbuminuria were significantly different between the patients and the control subjects (p = 0.001, p = 0.001, p = 0.002, and p = 0.005, respectively). There was a significant difference between groups in terms of the ratio of GG/GT+TT of eNOS gene Glu- 298Asp (p = 0.02). The patients with GT+TT genotype had significantly higher microalbuminuria levels and lower NO concentrations (22.16 vs. 9.51, p = 0.005, and 10.56 vs. 12.73, p = 0.021, respectively). The presence of T allele of eNOS gene is an independent predictor of microalbuminuria (OR: 2.346, 95% confidence interval: 1.247 - 5.238, p = 0.02) as well as serum glucose and NO concentration. The G894T polymorphism of eNOS gene and decreased NO concentration seem to be independent predictors of increased urinary excretion of albumin in patients with GDM. Determining the frequency of eNOS gene G894T polymorphism may help to identify pregnancies at increased risk of microalbuminuria.

Limbs’ postischemic revascularization is not improved by losartan treatment in diabetic rats

Most physiological actions of angiotensin II (Ang II) on cardiovascular system are mediated by angiotensin type 1 receptor (AT1R). Since peripheral artery disease is one of the most important complications of diabetes, in this study, we aimed to investigate the effect of losartan, an AT1R blocker, on skeletal muscle angiogenesis in diabetic hind limb ischemic rats. Twenty four male Wistar rats were randomly divided into four groups as follow: diabetic sham; diabetic sham + losartan (15 mg/kg/day); diabetic hindlimb ischemia; diabetic hindlimb ischemia + losartan. For induction of diabetes, streptozotocin was injected (55 mg/kg; i.p.). The animals were sacrificed after 21 days and the serum concentrations of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sFlt-1), nitric oxide (NO), capillary density, and capillary to fiber (cap⁄fib) ratio in ischemic legs were evaluated. The serum NO concentrations were significantly decreased, sFlt-1 concentrations increased, and VEGF concentrations did not significantly change after experiment in diabetic sham and diabetic hind limb ischemic rats. Administration of losartan did not induce significant changes in serum NO, sFlt-1, and VEGF concentrations (p>0.05). Capillary density and cap⁄fib ratio in ischemic leg of diabetic rats were not affected by losartan treatment (p>0.05). AT1R blocker, losartan, was not able to restore neovascularization in the ischemic leg of diabetic animals. Therefore, based on the present data, the losartan cannot be considered for treatment or prevention of peripheral artery disease in diabetic subjects.

The effects of beta-glucan rich oat bread on serum nitric oxide and vascular endothelial function in patients with hypercholesterolemia.

Introduction. Oats are high in soluble fibers and effective in reducing the risk of cardiovascular diseases (CVD). We assessed the effects of beta-glucan from oat bran on serum nitric oxide (NO) endothelial function in patients with hypercholesterolemia. Method. Sixty hypercholesterolemic patients were randomly divided to receive an experimental bread rich in beta-glucan from oat bran (intervention) or bread rich in wheat fiber (control) for four weeks. All subjects had the same diet for two-week baseline period and hypocaloric diet for four weeks of intervention. Serum NO concentration and flow-mediated dilation (FMD) were determined before and after the experiment. Results. Mean age of the participants was 51.1 ± 9.3 years and 65% (n = 39) were female. After intervention, serum NO concentration increased by 50.2 ± 19.8 μmol/lit in the intervention group (P = 0.017), but no change was observed in the control group (17.5 ± 27.5 μmol/lit; P = 0.530). No change of FMD was observed in the intervention (0.48 ± 0.78%; P = 0.546) or in the control group (0.59 ± 0.92%; P = 0.533). Conclusion. Consumption of oat bread for four weeks increases serum NO concentration but has no effect on FMD. Further studies are warranted in this regard.

Relationship of Progesterone, Bovine Pregnancy-Associated Glycoprotein-1 and Nitric Oxide with Late Embryonic and Early Fetal Mortalities in Dairy Cows

The aim of the present study was to determine the relationship of progesterone (P4), bovine pregnancy-associated glycoprotein-1 (bPAG-1) and nitric oxide (NO) levels with late embryonic (LEM; day 28 to day 42) and early fetal mortalities (EFM; > day 42 to day 56) in dairy cows. Transrectal ultrasonography (6–8 MHz) was performed in 100 Holstein-Friesian cows at days 28, 42 and 56 after artificial insemination (AI; day 0) to diagnose pregnancy and to monitor the fate of the embryo. After ultrasound scanning of each cow, a milk sample was collected for assessment of P4 by an ELISA test and a blood sample was collected for assessment of bPAG-1, by using a double-antibody radioimmunoassay, and serum NO metabolites (nitrate + nitrite). Based on ultrasonographic examinations and bPAG-1-RIA, 41 of 100 inseminated cows were confirmed pregnant at day 28 after AI. Nine cows suffered of LEM, and 6 cows suffered of EFM and the overall pregnancy loss rate was 36.6% (15/41) between days 28 and 56 of pregnancy. By logistic regression analysis, there were no significant relationships between the level of P4 and bPAG-1 at day 28 after AI and the occurrence of LEM and EFM. Also, there were no significant relationships between the levels of P4 and bPAG-1 at day 42 and the occurrence of EFM. On the other hand, a significant relationship (P<0.05) was found between NO level at day 28 and the occurrence of LEM. In conclusion, measurement of the serum NO concentration at day 28 of pregnancy might help to predict the outcome of pregnancy by day 42 in dairy cows but further studies are needed to confirm this.

Crosstalk between inflammation, iron metabolism and endothelial function in Behçet's disease

Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.

Protective Effect of L-carnitine on Metabolic Disorders, Oxidative Stress, Antioxidant Status and Inflammation in a Rat Model of Insulin Resistance

The high-fructose diet induces insulin resistance, hyperinsulinaemia, hyperglycemia, alterations in lipid metabolism, and oxidative stress in rat tissues which Oxidative stress plays a vital role in pathology associated with insulin resistance. The present study was aimed to explore the effect of L-carnitine (CAR) on insulin resistance, inflammation, oxidative stress, antioxidant status, and lipid metabolism in male rats fed with high fructose diet. Insulin resistance was induced by feeding high fructose diet (60 g/100 g). sixty male albino rats were divided into four groups containing 15 rats each. Group Ι:( Control group ) rats received the control diets. Group II (fructose-fed group) rats received fructoseenriched diet (60 g /100g). Group III: (fructose + CAR group) animals received high fructose diet and were administered CAR (300 mg/Kg body weight /day,orally). Group IV: (control +CAR group) rats received the control diet and were administered CAR. After 45 and 60 days of treatment blood samples and liver tissue were collected for determination of serum glucose, insulin, insulin resistance, pyruvate, lactate, leptin, total cholesterol, triacylglycerols, phospholipids, free fatty acids, sialic acid, tumor necrosis factorα (TNFα), interleukin-6 (IL-6) and nitric oxide in addition to Lmalondialdehyde (L-MDA). Moreover, antioxidant enzymes (SOD,CAT and GPx) in liver tissues were also determined. The obtained results revealed that, high fructose diet induce a significant increased in serum glucose, insulin, insulin resistance, lipid profiles, pyruvate, lactate, lipten, TNF-α, IL-6, sialic acid, MDA and nitric oxide concentrations and decrease serum phospholipids with marked reduction in CAT, SOD and GpX concentrations in liver tissues compared to rats fed normal diet. L-carnitine treatment to high fructose fed rats reduced the effects of fructose and associated with significant normalization of all serum parameters level and was able to improve dyslipidemia, inflammation and insulin resistance, attenuated the increased MDA and enhanced antioxidant status in liver tissues. These results suggest that, Lcarnitine is effective in improving the high fructose induced oxidative stress, inflammation and insulin resistance in male rats. Also, the administration of of L-carnitine to rats fed a high fructose diet prevents the development of oxidative stress and its associated complications include hyperglycemia , hyperinsulinemia and dyslipidemia.