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This research was designed to test the combined efficacy of hot water dipping (HWD) and leaf extracts of Cistus creticus L. subsp. creticus on the storage quality of fresh Valencia oranges. Experiments were laid down according to a completely randomised design with 10 different treatments. Five replications, with five fruits in each replication, were used in the current study, and research was designed to continue for 150 days. Quality characteristics were observed with 30-days interval. The applications of this study were (1) Control [dipping in water at 25°C for 5 min]; (2) HWD at 50°C for 5 min; (3) HWD + Additives (A) [Arabic gum (0.2%), potassium sorbate (0.05%), citric acid (0.05%) and vitamin C (0.05%)] at 50°C for 5 min; (4) Additives alone at 25°C for 5 min; (5) 1.0% C. creticus leaf + HWD + A; (6) 1.0% C. creticus leaf + A; (7) 0.5% C. creticus leaf + HWD + A; (8) 0.5% C. creticus leaf + A; (9) 0.5% C. creticus leaf + HWD and (10) 0.5% C. creticus leaf. According to the results obtained, both the HWD and C. creticus, alone or in combination, were effective in preserving orange weight during storage, preventing pathogenic decay, maintaining visual quality and fruit firmness, delaying the reduction in titratable acidity, increasing ascorbic acid content and reducing respiration rate of the orange fruits. Results also suggested that the combined effect of HWD with C. creticus leaf extracts provided the highest efficacy.

In this study, the effect of liver X receptor (LXR) activation on hypertension-induced cardiac structural and functional alterations was investigated. Hypertension was induced by deoxycorticosterone acetate (DOCA)-salt administration in uninephrectomized rats for 6 weeks. LXR agonist GW3965 (3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-amino]-propoxy}-phenyl)-acetic acid was given for the past week. Rhythmic activity and contractions of the isolated heart tissues were recorded. Biochemical parameters were assessed in ventricular tissue and plasma samples. Cardiac expressions of various proteins were examined, and histopathological evaluation was performed in the left ventricle and liver. GW3965 reduced systolic blood pressure and enhanced noradrenaline-stimulated papillary muscle contraction induced by DOCA-salt + uninephrectomy. Plasma and tissue total antioxidant capacity (TAC) increased and tissue 4-hydroxynonenal (4-HNE) levels decreased in the DOCA-salt group. GW3965 elevated plasma and tissue TAC levels in both of groups. Glucose-regulated protein-78 (GRP78), phospho-dsRNA-activated-protein kinase-like ER kinase (p-PERK), matrix metalloproteinase-2 (MMP-2), and nuclear factor-κB p65 (NF-κB p65) expression was augmented, and inhibitor-κB-α (IκB-α) expression was reduced in hypertensive hearts. The altered levels of all these markers were reversed by GW3965. Also, GW3965 ameliorated DOCA-salt + uninephrectomy-induced cardiac and hepatic inflammation and fibrosis. However, GW3965 unchanged the plasma lipid levels and hepatic balloon degeneration score. These results demonstrated that LXR activation may improve hypertension-induced cardiac changes without undesired effects.

Hypertension has complex vascular pathogenesis and therefore the molecular etiology remains poorly elucidated. Endoplasmic reticulum stress (ERS), which is a condition of the unfolded/misfolded protein accumulation in the endoplasmic reticulum, has been defined as a potential target for cardiovascular disease. In the present study, the effects of ERS inhibition on hypertension-induced alterations in the vessels were investigated. In male Wistar albino rats, hypertension was induced through unilateral nephrectomy, deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) and 1% NaCl with 0.2% KCI added to drinking water for 12 weeks. An ERS inhibitor, tauroursodeoxycolic acid (TUDCA) (150 mg/kg/day, i.p.), was administered for the final four weeks. ERS inhibition in DOCA-salt induced hypertension was observed to have reduced systolic blood pressure, improved endothelial dysfunction, enhanced plasma nitric oxide (NO) level, reduced protein expressions of phosphorylated-double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (pPERK), 78 kDa glucose-regulated protein (GRP78), Inositol trisphosphate receptor1 (IP 3 R1) and Epidermal growth factor receptor (EGFR), increased expressions of endoplasmic reticulum Ca 2+ -ATPase2 (SERCA2) and B cell lymphoma2 (Bcl2) in vessels. These findings suggest that the beneficial effects of ERS inhibition on hypertension may be related to protection of vessel functions through restoration of endoplasmic reticulum calcium homeostasis, and apoptotic and mitotic pathways., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Liver X receptors (LXRs) play an important role in the regulation of cholesterol, fatty acid and glucose metabolisms together with inflammatory processes. In the present study, the effects of LXR agonist GW3965 on vascular reactivity and expression of functional proteins in DOCA-Salt induced hypertension were examined., Main Methods: Hypertension was induced through unilateral nephrectomy and deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) for 6 weeks in male Wistar albino rats (8 weeks old). An LXR agonist GW3965 (10 mg/kg/day, i.p.) was administered to animals for last seven days., Key Findings: GW3965 treatment reduced systolic blood pressures in hypertensive rats. Acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent vasorelaxations were decreased in hypertensive rats but not affected by GW3965. GW3965 treatment enhanced plasma nitrite levels in normotensive rats. KCl and phenylephrine (Phe)-induced vasocontractions were reduced in hypertensive groups and increased with GW3965 treatment. Decreased sarco/endoplasmic reticulum Ca 2+ -ATPase2 (SERCA2) expression in the hypertensive aorta was not changed by GW3965 treatment. Expression of inositoltrisphosphate receptor1 (IP3R1) was increased by GW3965 in normotensive animals. The nuclear factor kappaB (NF-κB) and tumor necrosis factor alpha (TNF-α) expressions were increased in hypertensive rats and reduced by GW3965 treatment., Significance: The results of study indicate that the LXR agonist, GW3965, exhibited a beneficial effect on increased blood pressure and improved hypertension-induced impairment in contractile activity of vessel and inflammatory markers in vascular tissue. Therefore, these effects of LXR agonists on vessel should be taken into account in experimental or therapeutic approaches to hypertension., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of this long-term follow-up study was to investigate the association of local and systemic cardiovascular complications with endothelium-dependent and-independent microvascular relaxations and blood biomarkers and biochemicals in patients with peripheral arterial disease (PAD) caused by atherosclerosis., Methods: This prospective study included 67 patients with PAD who had not undergone any endovascular intervention, peripheral arterial surgery, or major amputation. Changes in the microvascular blood flow were measured using laser Doppler imaging after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). The biochemical markers of high sensitivity C reactive protein (hs-CRP), nitric oxide (NO), total antioxidant capacity (TAC), asymmetric dimethyl arginine (ADMA), and hydrogen sulfide (H2S) levels were measured from blood samples. All the patients were followed up for 5 years to determine the development of cardiovascular adverse events (CVAEs) and major amputation. At the end of the follow-up period, the patients were classified into two groups: those who had a CVAE [CVAE (+)] and those who did not experience CVAE [CVAE (-)]. Parameters such as demographic features, atherosclerotic risk factors, chronic ischemia category, microvascular endothelial functions, and plasma biomarkers were compared between the groups., Results: A total of 67 patients comprising 61 (91%) males and 6 (9%) females with a mean age of 62.3±9.7 years were included. During the follow-up period, 29 patients had CVAE (43.3%) and 38 patients did not have CVAE (56.7%). There was no difference between the groups in terms of ACh and SNP-induced vasodilation responses. Plasma high density lipoprotein (HDL) cholesterol values were lower in the CVAE (+) group [(CVAE+HDL: 38.4±9.1), (CVAE-HDL: 44.7±11.1), p=0.02]. Plasma hs-CRP values were significantly higher in the CVAE (+) group [(CVAE+ hs-CRP: 14.3±20.6), (CVAE-hs-CRP: 5.9±10.9), p=0.004]. No significant difference was observed between the groups in terms of plasma biomarkers and other biochemical levels., Conclusion: Based on the study findings, it was concluded that only low plasma HDL and high hs-CRP levels were risk factors for the development of CVAEs during follow-up of patients with PAD.

The purpose of this study was to determine the effects of resveratrol and regular aerobic exercise on vascular functions and biomarkers related to vessel responsiveness in an age and gender-dependent manner. The study used young (3 months) and old (12 months) male and female Wistar albino rats. Resveratrol was given in the drinking water (0.05 mg/ml; approximately 7.5 mg/kg) for 6 weeks. In the exercise group, all rats performed treadmill running at 20 m/min on a 0° incline, 40 min/day, 3 times a week, for 6 weeks. Acetylcholine-induced, endothelium-dependent and sodium nitroprusside-mediated, endothelium-independent relaxations of rat thoracic aorta and blood levels of biomarkers were separately changed by resveratrol intake and exercise-training in an age and gender-dependent manner. Antioxidant enzymes and eNOS expressions in vessels were elevated by resveratrol and exercise. Resveratrol and exercise enhanced gene expressions of non-selective PDE1, 2, 3 and cAMP selective PDE4 but not cGMP selective PDE5 in the aorta. In addition, the aortic mRNA expression of inflammation markers were altered by resveratrol and exercise-training. The results of the study demonstrated that vessel responsiveness and biomarkers related to vascular functions were altered by resveratrol consumption and exercise-training in an age and gender-dependent manner., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aging is a main risk factor for development of cardiovascular diseases associated with the impairment of endothelial function in both sexes. In the present study, age-related changes in vascular responsiveness, epigenetic modifications of vessel wall, and blood biomarkers related to endothelial functions were examined in an age- and sex-dependent manner. Acetylcholine (ACh)-induced relaxations of the aorta were decreased in 3-, 6-, and 12-month-old rats compared to those in 1-month-old female rats. In males, maximum relaxations related to ACh were higher in 1- and 6-month-old rats than in 3- and 12-month-old rats. Plasma levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA) decreased with age in female rats, and total antioxidant capacity (TAC) and hydrogen sulfide (H 2S) levels displayed biphasic alterations. In male rats, plasma levels of NO, TAC, and ADMA decreased with age, and H2S levels increased. Aging also caused a sex-dependent alteration in epigenetic modification of vessels. Expressions of H3K27me2, H3K27me3, H3K36me2, and H3K36me3 were much higher in vessels of 12-month-old female rats compared to those in younger age groups. These results indicate that vascular functions, epigenetic modifications of vessels, and plasma levels of endothelium-related biomarkers are affected by age and sex. These findings could be important for the assessment of vascular status over the course of the life span.

Shock is associated with inflammation-induced endothelial dysfunction. The aim of this study was to determine time-dependent alteration of blood biomarkers related to endothelial function in hemorrhagic and septic shocks. Hemorrhagic shock was induced by bleeding the animals. A cecal ligation and incision model was used to induce septicemia. Resuscitation was carried out by infusion of lactated Ringer's solution. Resuscitation extended survival time in both shock groups. Blood pressure increased by resuscitation in the hemorrhagic shock but not in the septic shock. While hemorrhage caused a decrease in plasma levels of nitric oxide (NO) and hydrogen sulfide (H 2 S), asymmetric dimethylarginine (ADMA) and total antioxidant capacity (TAC) levels were increased. Only NO and TAC levels at the late phase were reversed by resuscitation. On the other hand, plasma levels of NO, ADMA, and TAC were increased by septicemia and resuscitation did not alter the septicemia-induced increase. These results indicate that blood biomarkers related to endothelial function were differentially affected by hemorrhage and septicemia. The time scale of biomarker production should be taken into consideration for the diagnostic and therapeutic approaches to these life-threatening diseases.

Background: Intermittent ischemia in remote tissues can be applied before ischemic injury, during ischemic injury or at the beginning of reperfusion of an index organ ischemia. The aim of this study was to investigate the effect of Remote Ischemic Conditioning (RIC) of the leg on changes in ischemia-induced the microvascular functions of the arm., Material and Methods: Ischemic microvascular injury was induced by arm ischemia (20 min) and reperfusion in healthy, nonsmoker, male volunteers (ischemia group-ISC, n: 9). In another group of volunteers, to investigate the effects of remote organ ischemic conditioning 5 cycles of reperfusion followed by leg ischemia (each lasting 60 seconds) were applied either before (preRIC, n:11), or during (perRIC, n:12) or immediately after (postRIC, n:9) 20 minutes of arm ischemia. The microvascular flow of arm was assessed before and after ischemia using iontophoresis of the endothelium-derived nitric oxide (NO) releaser acetylcholine (ACh) and the endothelium-independent NO donor sodium nitroprusside (SNP). Changes in microvascular blood flow were measured using Laser Doppler imaging. The plasma level of biomarkers related to endothelial function such as nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulphide (H2S) were measured., Results: No difference was determined between the groups in terms of age, BMI or blood biochemicals reflecting cardiovascular status. ACh caused a rise in microvascular blood flow in a charge dependent manner. The ACh-induced flow increase was not significantly depressed by ischemia and not affected by any of the types of RIC in the study subjects. The increase in SNP-induced microvascular flow was significantly decreased in the ISC, perRIC and postRIC groups, but not in the preRIC group. Plasma levels of NO, ADMA, TAC and H2S were not changed by ischemia and RIC., Conclusion: These results suggested that microvascular perfusion of human forearm skin was elevated by either endothelium or drug-derived NO. The effect of ischemia and RIC on NO-induced flow increase was affected differently by different applications in the healthy young individuals. These complicated results are taken into consideration in experimental and therapeutic interventions.

At present there is no widely accepted biomarker for monitoring of vascular functions. The purpose of this prospective study was to investigate the association of some blood biomarkers with vascular reactivity in patients with peripheral arterial diseases (PAD). A prospective evaluation was made of 3 groups comprising a control group of healthy individuals, and patients with PAD caused by either atherosclerosis or Buerger's disease. Microvascular perfusion was examined using laser Doppler imaging of cutaneous erythrocyte flux after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). The correlation of microvascular reactivity with endothelium-related biomarkers was assessed. ACh-induced and SNP-induced vasodilations were significantly diminished in the PAD groups. The plasma nitric oxide (NO) levels of PAD patients were significantly higher than those of the control group, but asymmetric dimethylarginine, total antioxidant capacity and hydrogen sulphide levels were similar. Plasma NO level was negatively correlated with ACh and SNP-stimulated microvascular flow increase, whereas a positive correlation was detected with blood glucose and glycated hemoglobin (HbA1c) levels in all groups. These results indicate that a high plasma level of NO in PAD patients is associated with diminished endothelium-dependent and independent flow increase in the microvascular bed. An excessive amount of NO-induced nitrosative stress in an inflammatory condition that might be a reason for vascular dysfunction should be taken into consideration in the diagnostic and therapeutic approaches to PAD.

Hypertension is a risk factor for the cardiovascular diseases. Although, several drugs are used to treat hypertension, the success of the antihypertensive therapy is limited. Resveratrol decreases blood pressure in animal models of hypertension. This study researched the mechanisms behind the effects of resveratrol on hypertension. Hypertension was induced by using the deoxycorticosterone acetate (DOCA)-induced (15 mg/kg twice per week, subcutaneously) salt-sensitive hypertension model of Wistar rats. Hypertension caused a decrease in endothelium-dependent relaxations of the isolated thoracic aorta. Resveratrol treatment (50 mg/l in drinking water) prevented DOCA salt-induced hypertension, but did not improve endothelial dysfunction. Plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulfide (H2S) levels were not changed by DOCA salt application. However, treatment of resveratrol significantly decreased ADMA and increased TAC and H2S levels. NO level in circulation was not significantly changed by resveratrol. DOCA salt application and resveratrol treatment also caused an alteration in the epigenetic modification of vessels. Staining pattern of histone 3 lysine 27 methylation (H3K27me3) in the aorta and renal artery sections was changed. These results show that preventive effect of resveratrol on DOCA salt-induced hypertension might due to its action on the production of some blood biomarkers and the epigenetic modification of vessels that would focus upon new aspect of hypertension prevention and treatment.

Pulmonary hypertension (PH) is a life-threatening disease that causes endothelial dysfunction in the pulmonary vascular bed. Systemic endothelial dysfunction has also been reported in PH. This study compared the systemic and pulmonary vascular responses and some blood biomarkers of endothelial function in monocrotaline (MCT)-induced PH of rats. It also investigated the effect of sildenafil and iloprost treatment. MCT application induced elevation in the right ventricular pressures of the rat heart that had been reversed by sildenafil and iloprost treatment. Acetylcholine-induced endothelium-dependent relaxations of the isolated pulmonary artery were decreased in the PH group and this failure was reversed by sildenafil and iloprost treatment. Acetylcholine-induced endothelium-dependent relaxations of the isolated thoracic aorta were similar in all groups. Serotonin-induced contractions of the pulmonary artery were augmented by PH. In the isolated aorta, serotonin-stimulated contraction was not different in the control and MCT groups, but sildenafil and iloprost treatment decreased serotonin responses. The nitric oxide (NO) level in systemic circulation was not significantly changed by PH. However, sildenafil and iloprost treatments caused a decrease in the plasma level of NO. Asymmetric dimethylarginine levels in plasma were significantly decreased after MCT application and were not recovered by sildenafil and iloprost treatment. Total antioxidant capacity and H2S level of plasma were similar in all groups. Results of this study showed that MCT-induced PH caused specific toxic effects on pulmonary vasculature without any functional effects on the aorta. In addition, it was also demonstrated that sildenafil and iloprost treatments were effective in the MCT-induced PH.

In this study, the effects of acute and subacute formaldehyde (FA) exposures on spontaneous locomotor activity (SLMA), wet dog shake (WDS) behavior and pentylenetetrazole (PTZ) induced seizures were evaluated in Balb/C mice. SLMA was concentration dependently reduced after acute FA exposures at 1.8, 3.2, 4.5, 6.4, 9.7, and 14.8 ppm. The incidence of WDS behavior was increased only after acute FA exposures at 1.8, 3.2 and 6.4-ppm. PTZ-injections caused more intensive seizures in mice acutely exposed to FA only at 1.8 ppm. Meanwhile, the incidence of PTZ induced seizures was significantly lower after acute FA exposure at 14.8 ppm. SLMA was also reduced after subacute FA exposure at 2.0 ppm for 3 weeks. The inhibitory effects were significant after 1-week exposure at this concentration, but a tolerance developed at the end of the second week. As the concentration increased to 3.2 ppm, SLMA has found to be reduced after 2-week exposure. There was no change either on the incidence of WDS or on the parameters of PTZ-induced seizures, due to the subacute exposures of FA at the respective concentrations. In conclusion, based upon these data, acute and subacute exposures of FA produce a significant behavioral depression on mice. The data also suggest that acute FA exposures at low concentrations (such as 1.8 ppm) may increase the excitability of central nervous system (CNS).

Changes in serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA), its major metabolite, in cerebral cortex, corpus striatum and hippocampus were investigated at 10th and 21st days of chronic ethanol ingestion in Wistar rats. Ethanol (7.2% v/v) was given to rats in a modified liquid diet. Biochemical analysis was performed in two groups of ethanol-treated and control rats (n = 6 for each group). Rats in each group were decapitated at the 10th and 21st days of ethanol consumption. Brains were removed and cerebral cortex, corpus striatum and hippocampus were dissected. 5-HT and 5-HIAA levels were measured in respective brain regions by using high performance liquid chromatography. In cerebral cortex and corpus striatum, 5-HT levels were significantly lower than control at the 10th day of ethanol consumption. At the 21st day, the levels tended to remain low, but not significantly different statistically. In hippocampus, 5-HIAA levels were significantly higher than control at 10th day of ethanol consumption. Increased 5-HIAA level returned to control values at the 21 st day of ethanol consumption. Our results suggest that, 5-HT clearly seems to play a critical role in the brain at the 10th day of chronic ethanol consumption.

Changes in dopaminergic and serotonergic levels and metabolites in cerebral cortex, corpus striatum and hippocampus were investigated during the first 6-h of withdrawal in ethanol-dependent Wistar rats. Ethanol was given by a liquid diet for 21 days. The concentration of ethanol was 7.2% (v/v) for the last 15 days of the exposure. After 2, 4 and 6 h of ethanol withdrawal, and after audiogenic stimulus (100 dB for 60 s) at 6 h of ethanol withdrawal, various brain regions were assayed for levels of dopamine (DA), DOPAC, HVA, serotonin (5-HT) and 5-HIAA. Behavioral signs of ethanol withdrawal and blood ethanol levels were also evaluated in other parallel groups of ethanol-dependent rats. Significant decreases in 5-HT levels and significant increases in HVA levels in striatum were found during the first 6 h of ethanol withdrawal and after the audiogenic seizures. In hippocampus, 5-HIAA levels were significantly reduced after 2 h of ethanol withdrawal and after the audiogenic seizures. 5-HIAA levels significantly increased after 2 h of ethanol withdrawal in cerebral cortex. Significant increases in both DA and 5-HT levels were also found in cerebral cortex after the audiogenic seizures. The results suggest that the levels of DA, 5-HT and their metabolites are altered by ethanol withdrawal. Furthermore, this may suggest that DA and 5-HT may be involved in the first 6 h of ethanol withdrawal syndrome in rats.