Pre-treatment with pregabalin reduces liver ischemia-reperfusion injury in rats: tissue protection with an analgesic.

OBJECTIVE: Ischemia-reperfusion injury is thought to be the most important factor affecting the success of liver surgery. Pregabalin has been studied to prevent ischemic reperfusion injury in many organs. The aim of this study was to investigate the role of pregabalin in preventing liver ischemic injury. MATERIALS AND METHODS: 40 male Wistar-Albino rats, 6-8 weeks old, were divided into 5 groups. Four groups other than the sham group were subjected to hepatic ischemia for 1 hour, followed by 2 hours of reperfusion. Effects of 30 mg/and 60 mg/kg pregabalin were evaluated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor α (TNF-α), nuclear factor-kappa B (NF-кB), interleukin (IL)-6 levels, measured in blood samples collected before and after ischemia. Apoptosis was measured by caspase-3, and tissue samples were evaluated for ischemia by histopathologic examination. RESULTS: The 60 mg pregabalin group was significantly superior (p=0.024) to the N-acetylcysteine group and the 30 mg pregabalin group for AST levels (p=0.612 and p=0.807, respectively). The difference between before and after ischemia-reperfusion blood TNF-α levels was higher in the 60 mg pregabalin group, but not significantly different from the 30 mg pregabalin and N-acetylcysteine groups (p>0.05). Tissue TNF-α levels showed that 60 mg and 30 mg pregabalin treatment was more effective than no-treatment (p=0.011, p=0.033, respectively), but not superior to N-acetylcysteine (p>0.05). CONCLUSIONS: It has been found that ischemia-reperfusion causes damage to the liver, and this damage may be irreversible if no treatment is given. Our study group, pregabalin molecule was found to be significantly effective in preventing ischemia-reperfusion injury and may have a therapeutic advantage over N-acetylcysteine.

Empagliflozin and sacubitril/valsartan reverse methotrexate cardiotoxicity by repressing oxidative stress and hypoxia in heart embryonic H9c2 cardiomyocytes - the role of morphology of mitochondria observed on electron microscopy.

OBJECTIVE: Oxidative stress and hypoxia play an important role in the pathogenesis of various cardiovascular diseases. We aimed to evaluate the effectiveness of sacubitril/valsartan (S/V) and Empagliflozin (EMPA) on hypoxia-inducible factor-1α (HIF-1α) and oxidative stress in H9c2 rat embryonic cardiomyocyte cells. MATERIALS AND METHODS: BH9c2 cardiomyocyte cells were treated with methotrexate (MTX) (10-0.156 µM), empagliflozin (EMPA; 10-0.153 µM) and sacubitril/valsartan (S/V; 100-1.062 µM) for 24, 48 and 72 h. The half maximum inhibitory concentration (IC50) and half maximum excitation concentration (EC50) values of MTX, EMPA and S/V were determined. The cells under investigation were exposed to 2.2 µM MTX before treatment with 2 µM EMPA and 25 µM S/V. The cell viability, lipid peroxidation, oxidation of proteins and antioxidant parameters were measured while morphological changes were also observed by transmission electron microscopy (TEM). RESULTS: The results showed that treatment with 2 µM EMPA, 25 µM S/V or their combination produced a protective effect against the reduction in cell viability caused by 2.2 µM MTX.  While HIF-1α levels plunged to their lowest with S/V treatment, oxidant parameters dipped, and antioxidant parameters soared to their highest level with S/V and EMPA combination treatment. A negative correlation was found between HIF-1α and total antioxidant capacity in the S/V treatment group. CONCLUSIONS: A significant decrease in HIF-1α and oxidant molecules together with an enhancement in antioxidant molecules and normalization of the mitochondria morphology as observed on electron microscopy in S/V and EMPA-treated cells were detected. Although S/V and EMPA have both protective effects against cardiac ischemia and oxidative damage, this effect may be increased more with S/V treatment alone compared to combined treatment.

Ranolazine exhibits anti-inflammatory and antioxidant activities in H9c2 cardiomyocytes.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of ranolazine on hypoxia-inducible factor-1α (HIF-1α) and oxidative stress in H9c2 cardiomyocyte cells. MATERIALS AND METHODS: We have assessed the effects of increasing concentrations of methotrexate (MTX) and ranolazine on proliferation of H9c2 rat cardiomyocyte cells by MTT assay. Malondialdehyde (MDA) protein oxidation [advanced oxidation protein products (AOPPs)], lipid hydroperoxide (LOOH) and xanthine oxidase (XO) activity as oxidative stress markers and HIF-1α levels increased and total thiol (T-SH), catalase (CAT) activity and total antioxidant capacity (TAC) antioxidant capacity markers decreased in MTX-treated cells compared to control cells. RESULTS: Oxidative stress markers decreased, and antioxidant capacity markers increased in cells treated with ranolazine alone compared to control cells. For all parameters, we showed that the levels of oxidant, antioxidant markers and HIF-1α in cells treated with MTX and ranolazine together reached the level of the control group, and ranolazine reversed the oxidative damage caused by MTX. CONCLUSIONS: The cell viability increased the levels of oxidant and prooxidant markers and decreased the levels of antioxidant markers decreased in H9c2 cardiomyocytes induced by oxidative stress. These results suggest that ranolazine may protect the cardiomyocytes from MTX-induced oxidative damage. The effects of ranolazine could result from its antioxidant properties.

CIRCULATING MIR-132, MIR-146A, MIR-222, AND MIR-320 EXPRESSION IN DIFFERENTIAL DIAGNOSIS OF WOMEN WITH POLYCYSTIC OVARY SYNDROME.

Purpose: The aim of the study was to investigate whether the circulating miR-132, miR-146a, miR-222, and miR-320 levels are used in the differential diagnosis of women with polycystic ovary syndrome (PCOS) and healthy women. Methods: This prospective case-control study included 50 women with PCOS and age- and body mass index- matched 50 healthy controls. The hormone and lipid profiles, levels of microRNAs (miRNAs), and parameters of carbohydrate metabolism were measured. Results: Expression levels of miRNAs were assessed using the two-step quantitative real-time polymerase chain reaction. Circulating miR-132, miR-146a and miR-222 levels were significantly downregulated in the PCOS group compared with the control group. The miR-320 levels did not differ between the two groups. Free testosterone was negatively correlated with miR-132, miR-146a and miR-222. Insulin was negatively correlated with miR-132 and miR-146a. Conclusions: The results of the study revealed that miRNA expression, may suggest a possible distinction between healthy women and PCOS patients. miR-132, miR-146a, and miR-222 may have key functions in the pathogenesis of PCOS.

The role of laparoscopic sleeve gastrectomy on inflammatory parameters in morbidly obese patients.

BACKGROUND: Obesity is an excessive increase in body fat mass and triggers chronic inflammation which causes increased fat accumulation in the visceral fat tissue. The aim of this study was to analyze serum zinc (Zn), Zn-alpha 2 glycoprotein (ZAG), peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) levels in morbidly obese patients before and after laparoscopic sleeve gastrectomy (LSG) and determine the association between alteration in body mass index (BMI), the % Excess Weight Loss (% EWL) and the biochemical parameters. METHODS: Thirty healthy individuals as a control group and 30 morbidly obese patients who had undergone LSG were enrolled in this study. Routine anthropometric and laboratory biochemical parameters in venous blood samples of groups at baseline and 1 and 12 months after LSG were recorded. RESULTS: Significant weight loss was achieved at 1 and 12 months after LSG. At baseline serum ZAG and PPAR-γ levels were lower, while NF-кB levels were higher in morbidly obese patients compared with the control group. Serum ZAG and PPAR-γ levels increased while NF-кB levels decreased 1 month and 12 months after LSG. Decreased %EWL was negatively correlated with changes in NF-кB, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting plasma glucose and insulin at 12 months after LSG in morbidly obese patients. However, %EWL was positively correlated with changes in ZAG. CONCLUSIONS: Obesity was associated with down-regulated serum ZAG and PPAR-γ levels while up-regulated serum NF-кB. Our findings suggest that LSG ameliorates upregulating PPAR-γ expression, thereby inhibiting NF-κB-mediated inflammation by weight loss.

Combined nerve, vessel, and tendon injuries of the volar wrist: Multidisciplinary treatment and functional outcomes.

The superficial location of critical structures, including tendons, nerves and vessels, in the volar surface of the wrist makes them vulnerable to penetrating trauma. Extensive injuries to these structures are described as "spaghetti wrist". The main objective of this study was to report functional outcome in spaghetti-wrist injuries. The records of patients presenting to our clinic with extensive volar wrist injuries between January 2016 and January 2019 were reviewed retrospectively. Age, gender, comorbidities, date of injury, injury mechanism, affected hand and transected structures were noted. Tendon function, opposition, intrinsic hand function, deformity and sensitivity were evaluated following the Noaman report. The Michigan Hand Outcomes Questionnaire (MHOQ) was used to evaluate hand-specific outcomes. Twenty patients were included. Mean age was 32.7 years (range, 18-47 years). Mean follow-up was 21.9 months (range, 12-50 months). Mean number of injured structures was 11.9 (range, 10-16 structures) per patient. Physiotherapy duration had an effect on postoperative outcome in all six MHOQ domains (r = 0.821, p = 0.00001). However, no significant difference in overall hand function was found according to the number of injured structures (r = -0.105, p = 0.661). Precise initial evaluation, meticulous surgical treatment within 24 h and early physical therapy are essential after spaghetti-wrist injury. Good functional results are associated with prolonged physical therapy, but not with the number of structures injured.

The importance of circulating levels of salusin-α, salusin-ß, and heregulin-ß1 in atherosclerotic coronary arterial disease.

OBJECTIVE: The relationship between the severity of atherosclerotic coronary artery disease (CAD) and circulating levels of salusin-α, salusin-ß and heregulin-ß1 has been investigated. In addition, the relationship with these peptides and high sensitive C-reactive protein (hsCRP) has been investigated. METHODS: The study was conducted on 55 volunteers who had normal coronary angiography (CAG) as the control group, 35 volunteers with the degree of coronary artery stenosis below 50% in CA as the non-critical stenosis group, 37 volunteers with narrowing of one coronary artery above 50% as single vessel group and 41 volunteers with narrowing of more than one coronary artery above 50% as multi-vessel group. One hundred and thirteen volunteers have been included to CAD group. RESULTS: There was no statistically significant difference in serum salusin-α levels between groups. Serum salusin-ß ve hsCRP levels were significantly lower in control group compared to other groups and CAD group. There was no statistically significant difference in salusin-ß and salusin-α levels in reciprocal comparison of other groups other than heregulin-ß1 levels. Heregulin-ß1 levels were significantly lower in 'non-critical occlusion' and 'multiple artery occlusion' groups compared to control group. Heregulin-ß1 levels in 'single artery occlusion' group were significantly higher than control, 'non-critical occlusion' and 'multiple artery occlusion' groups. CONCLUSION: Salusin-α levels does not indicate any significant differences between any groups in our study however the relationship of salusin-α with salusin- ß and heregulin-ß1 levels drives to cogitate that these peptides can be used as biomarkers and therapeutic approaches in CAD. We think that these peptides will be used in laboratories routinely in future in addition to hsCRP for CAD.

The relationship between carotid intima-media thickness and serum secreted frizzled-related protein-4 and dipeptidyl peptidase-4 in diabetic patients with cardiovascular diseases.

We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). This study consisted of four groups: control group (mean ages: 50.3±10.7 years; 20 females and 15 males), diabetic group (DM; mean ages: 53.9±11.1; 14 females and 23 males), CAD group (mean ages: 60.1±43.5; 17 females and 17 males) and CAD+DM group (mean ages: 62.6±11.8 years; 18 females and 18 males). CIMT levels in both CAD and CAD+DM groups are higher than those in controls. CIMT levels in CAD+DM group are also significantly higher than those in DM group. Left external carotid artery (ECA) was found different from controls only in DM group. The levels of SFRP-4 in control group were significantly lower than those in DM, CAD and CAD+DM groups. Serum GLP-1total levels were found to be significantly low in CAD+DM group when compared to control group. DPP-4 and SFRP-4 levels may be a predictive marker for atherosclerosis in diabetes while particularly in diabetes, they correlate well with HOMA-IR. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD (Tab. 3, Fig. 2, Ref. 39). Keywords: type 2 diabetes mellitus, carotid intima-media thickness, glucagon-like peptide-1, dipeptidyl peptidase-4, clusterin, amylin, secreted frizzled-related protein-4.

Disinfection byproduct precursor dynamics and water treatability during an extreme flooding event in a coastal blackwater river in southeastern United States.

Coastal blackwater rivers, characterized by high concentrations of natural organic matter, are source water for millions of people in the southeastern US. In October 2015, large areas of coastal South Carolina were flooded by Hurricane Joaquin. This so-called "thousand-year" rainfall mobilized and flushed large amounts of terrestrial organic matter and associated pollutants (e.g. mercury) into source water, affecting water quality and safety of municipal water supply. To understand the dynamics of water quality and water treatability during this extreme flood, water samples were collected from Waccamaw River (a typical blackwater river in the southeastern US) during rising limb, peak discharge, falling limb, and base flow. Despite decreasing water flow after peak discharge, dissolved organic carbon (DOC) levels (increased by up to 125%), and formation potentials of trihalomethanes and haloacetic acids (increased by up to 150%) remained high for an extended period of time (>eight weeks after peak discharge), while variation in the N-nitrosodimethylamine (NDMA) FP was negligible. Coagulation with alum and ferric at optimal dosage significantly reduced concentrations of DOC by 51-76%, but up to 10 mg/L of DOC still remained in treated waters. For an extended period of time, elevated levels of THMs (71-448 µg/L) and HAAs (88-406 µg/L) were quantified in laboratory chlorination experiments under uniform formation conditions (UFC), exceeding the United States Environmental Protection Agency's (USEPA) maximum contaminant level of 80 and 60 µg/L, respectively. Results demonstrated that populations in coastal cities are at high risk with disinfection by-products (DBPs) under the changing climate.

Pentraxin-3 levels are associated with vasculitis and disease activity in childhood-onset systemic lupus erythematosus.

Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications. Results Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p < 0.001). PTX3 concentrations were also in correlation with SLEDAI-2K ( r = 0.57, p < 0.001). When viewed from the clinical perspective, serum PTX3 levels were significantly higher only in patients with active vasculitis ( p < 0.001), Raynaud phenomenon ( p = 0.006) and mucocutaneous manifestations ( p < 0.001). However, an association between PTX3 and age, age at disease onset, disease duration, complement levels, PedSDI score (pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected. Conclusions Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity.

Negative pressure wound therapy in the early period after hand and forearm replantation, is it safe?

OBJECTIVE: In this study, effectiveness and reliability of negative pressure wound therapy (NPWT) in the early period after replantation will be examined retrospectively in a series of patients. METHOD: Patients who underwent replantation between 2007 and 2014, and had tissue defect or partial necrosis in the absence of a major circulation problem were included in this retrospective study. Following debridement of necrotic tissues on the postoperative 7-10 days, NPWT was applied to all patients one day later and adjusted as intermittent 75 mmHg pressure. Intermittent phase adjustment was arranged as 5 minutes suction and 2 minutes resting, and resting pressure was adjusted as 35 mmHg. NPWT was applied for six days and dressings were changed in every three days in the first six day period. Open wounds was debrided again and grafted with split-thickness skin graft and NPWT was continued over the graft for 4 days more. RESULTS: There were 11 patients included of which nine amputations were complete and two were nearly total amputations of forearm. Granulation tissue was observed following 6 days of NPWT application in all patients. Graft survival was observed to be almost complete. Wound infection did not occur and tissue cultures obtained in the course of debridement were all negative. Partial oxygen saturations were between 96-99% during the NPWT. CONCLUSION: NPWT (75 mmHg) can be used in the intermittent mode in order to improve wound healing and shorten the period to start physical therapy in the early period after replantation and revascularisation.

The association of vascular endothelial growth factor, metalloproteinases and their tissue inhibitors with cardiovascular risk factors in the metabolic syndrome.

OBJECTIVE: The present study was proposed to examine the matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and vascular endothelial growth factor (VEGF) in patients with metabolic syndrome (MetS), and to compare these parameters with healthy controls. We also compared the possible association of the circulating levels of MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF with cardiovascular risk factors in patients with MetS. We also compared the possible association of the circulating levels of MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF with cardiovascular risk factors in patients with MetS. PATIENTS AND METHODS: A total of 45 patients with MetS and 17 healthy controls with a body mass index (BMI) less than 25 kg/m2 were enrolled in the study. Plasma MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF levels were determined using ELISA. RESULTS: TIMP-1,-2, MMP-2,-9 levels were significantly higher in patients with MetS compared with healthy controls (p < 0.001). Carotid intima-media thickness and serum VEGF levels were found to be significantly increased (p < 0.01, p < 0.05 respectively) in MetS compared with healthy controls. According to the ROC curves, TIMP-1 levels were both sensitive (93.3%) and specific (81.2%). CONCLUSIONS: We observed that the patients with MetS have increased circulating concentrations of MMP-9, MMP-2, and TIMP-1, TIMP-2 that are associated with increased concentrations of VEGF. These findings suggest that MMP-2 may have a role in the increased cardiovascular risk of MetS patients.

Evaluation of matrix metalloproteinase, myeloperoxidase, and oxidative damage in mesenteric ischemia-reperfusion injury.

BACKGROUND: In this study, we investigated the alterations of matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMPs), acute inflammation, and oxidative damage in the circulatory system and the intestine in response to mesenteric ischemia/reperfusion (I/R). METHODS: Twenty-one rats were divided randomly into the following three groups (n = 7 in each group): a sham group (CG), an ischemic group (IG), and an I/R group (I/RG). MMP-9, TIMP-1, and myeloperoxidase (MPO) were measured using the enzyme-linked immunosorbent assay method, and lipid peroxidation (quantified as thiobarbituric acid reactive substances (TBARS) content), ischemia-modified albumin, the prooxidant-antioxidant balance (PAB), and ferric-reducing antioxidant power (FRAP) were measured spectrophotometrically. The degree of intestinal injury was evaluated according to the Chiu scoring system. RESULTS: A significant difference between the mean serum TIMP-1 and MMP-9 levels and the alanine transaminase activity was found among the groups. Compared with the I/RG group a significant difference in the mean tissue MMP-9, MPO, and TBARS levels in addition to the PAB and FRAP was found between the CG and IG groups. The level of MMP-9 also demonstrated a strong, positive, and valid correlation with the TBA-RS levels. A significant morphological change was observed in both the IG and the I/RG groups. The degree of intestinal injury was more severe in the I/R group and was characterized by either villous denudation or villous loss. CONCLUSIONS: These results suggest that MMP-9, TIMP-1, MPO, and oxidative stress may be important in the intestinal injury development that is induced by acute mesenteric I/R in a rat model. MMP-9 overexpression may increase the extent of intestinal villous loss, particularly when MMP-9 is upregulated by the TBARS present in the intestinal injury.

Evaluation of the antioxidant effects of melatonin on the larynx mucosa of rats exposed to environmental tobacco smoke.

OBJECTIVES: This study's aim was to investigate the effect of melatonin in terms of mitigating the effects of smoking on the laryngeal mucosa of rats exposed to environmental tobacco smoke. DESIGN: Rats were divided into four groups: Melatonin + Smoking group exposed to smoke with melatonin; Smoking group exposed to smoke without melatonin; Saline group not exposed to smoke without melatonin; Melatonin group not exposed to smoke with melatonin. CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were evaluated in plasma and tissues. Tissues were also examined the changes of squamous hyperplasia, keratosis, parakeratosis and epithelial hyperplasia by light microscope and the ultrastructural changes by electron microscope. RESULTS: Tissue SOD, CAT and GSH-Px activities were significantly higher in Saline and Melatonin groups than Melatonin + Smoking and Smoking groups. Plasma CuZn-SOD and CAT activities were significantly higher in Saline and Melatonin groups than Smoking group. Plasma GSH-Px showed no significant difference. The rate of epithelial hyperplasia was significantly higher in Smoking group than the other groups. The rate of parakeratosis was significantly higher in Smoking group than the other groups. The epithelial cells in Melatonin + Smoking group displayed, normal cell structure similar to those in Saline group under electron microscope. CONCLUSIONS: The study shows that smoking induces substantial pathological changes in the laryngeal mucosa and melatonin may have some beneficial effects in partially reversing smoking-induced laryngeal injury by inducing the expression of antioxidants; biochemical and histological outcomes also support these findings due to preventing tissue damage in laryngeal mucosa exposed to smoke.

Procalcitonin and Pentraxin-3: Current biomarkers in inflammation in white coat hypertension.

An association has been described between inflammation and the progression of hypertension (HT) and is shown with several biochemical parameters. Our aim was to examine the distribution of the serum procalcitonin (PCT), pentraxin (PTX)-3 and interleukin (IL)-33 levels and their relationship with carotid intima-media thickness (CIMT) in subjects with white coat HT (WCH), HT and normotension (NT) groups. Thirty-three patients with HT, 33 patients with WCH and 33 healthy subjects were enrolled in this study. PCT, PTX-3 and C-reactive protein (CRP) levels significantly increased in the HT group compared with the NT group. In addition, PCT and CRP levels were significantly higher in the WCH group than in the NT group. CIMT measurements were significantly higher in the WCH and HT groups than in the NT group. In the HT and WCH groups, there were significant positive correlations between PTX-3, PCT and CRP. In the WCH group, PTX-3 and PCT levels were significantly positively correlated with CIMT. PCT had area under the curve value of 0.817 which demonstrates its sufficiency to distinguish WCH from NT individuals. Our results suggest that in subjects with WCH and HT, which are characterized by increased cardiovascular risk, PTX-3 and PCT levels in the HT group and PCT levels in the WCH group are significantly and consistently higher than normotensives. Systemic inflammation moderately occurs in the WCH and HT groups. PCT monitoring may be a useful biomarker in inflammation related to atherosclerosis and early stage HT.

Endothelial damage in white coat hypertension: role of lectin-like oxidized low-density lipoprotein-1.

The aims of this study included an examination of soluble lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (sLOX-1) levels in hypertensive (HT) patients. Another aim examined sLOX-1 associations with oxidized LDL (oxLDL), nitric oxide synthase (eNOS) and nitric oxide (NOx). A final aim was to compare these parameters between HT patients, white-coat hypertensive (WCH) patients and healthy controls. The three groups, HT, WCH and controls, were comprised of 35 patients each. sLOX-1 and oxLDL levels were significantly increased in WCH and HT patients compared with controls. The eNOS activation was significantly lower in HT than in the control group. sLOX-1 and oxLDL levels were significantly negatively correlated with eNOS levels in the WCH and HT groups. Carotid intima-media thickness (CIMT) measurements were significantly higher in the WCH and HT groups compared with controls. There was a significant positive correlation between CIMT and sLOX-1 and oxLDL; however, there was a negative correlation with eNOS in WCH. Regression analysis revealed that sLOX-1 was the variable that had a significant effect on blood pressure (P<0.001, odds ratio (95% confidence interval=23.273 (5.843-92.688)). A possible endothelial impairment may act as a cardiovascular risk factor in WCH. Necessary measures should be considered in terms of atherosclerosis risk with HT, especially in early identification of endothelial damage by looking at sLOX-1 levels. We believe sLOX-1 levels are strong biomarkers for determining early endothelial damage in HT, and especially in WCH patients.

Soluble Lectin-Like Oxidized LDL Receptor 1 as a Possible Mediator of Endothelial Dysfunction in Patients With Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) defines a well-known cluster of metabolic disturbances associated with an increased risk of cardiovascular disease and diabetes. The aim of this study was to examine the distribution of soluble lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (sLOX-1) levels in patients with MetS, possible association of sLOX-1 with oxidized LDL (oxLDL), endothelial nitric oxide synthase (eNOS), nitric oxide (NOx), endothelin-1 (ET-1), paraoxonase 1 (PON1), and arylesterase (ARE) activities, and these parameters compared with healthy controls. METHODS: A total of 55 patients (37 women, 18 men) with MetS and 29 healthy controls (19 women, 10 men) with a body mass index (BMI) less than 25 kg/m(2) were enrolled in the study. RESULTS: sLOX-1, oxLDL, and ET-1 levels were significantly higher in patients with MetS than in control subjects (P = 0.023 P < 0.001, and P < 0.001, respectively). MetS patients have significantly lower eNOS and NOx levels, and PON1 and ARE activities than control subjects (P = 0.017, P < 0.004, P < 0.001, and P = 0.010, respectively). A positive correlation was observed between the sLOX-1 levels and the oxLDL, ET-1, BMI, glucose levels. ET-1 levels also exhibited significant negative correlation with ARE activity. CONCLUSION: sLOX-1 levels are associated with cardiovascular risk factors, such as increased oxLDL, obesity, and diabetes, in patients with MetS. An increased concentration of sLOX-1 could be an early predictor of endothelial damage in MetS. In addition, it appears that oxLDL, ET-1, eNOS, NOx, PON1, and ARE activities may accurately reflect the levels of endothelial dysfunction in MetS patients.

Nitric oxide mediated effects of nebivolol in myocardial infarction: the source of nitric oxide.

OBJECTIVE: After MI pathological LV remodeling is one of the major causes of death. We previously showed the NO mediated beneficial effects of nebivolol in rat MI model, in this study we aimed to evaluate the NOS related mechanisms in this phenomenon. MATERIALS AND METHODS: Rats were divided into four groups: sham operated (sham-control), MI-induced (MI-control), immediate nebivolol loaded (MI-neb1), orally nebivolol treated (MI-neb2). MI was induced by the ligation of the LAD. Loading dose of nebivolol (0.1 mg/kg) was administrated i.v. during reperfusion and continuation dose was administrated orally (2 mg/kg) by gastric gavages once daily. NOS related mechanisms were assessed either in acute (2nd day) and sub-acute (28th day) period of MI by histologic, hemodynamic and biologic studies. RESULTS: Compared to MI-control rats, physiological functions of LV (LVEDP, Δ±dp/dt) were prevented in both nebivolol treated groups. Improvements in anatomical parameters (LEV, HW, LVW/HW) were consistent with functional improvement too. Moreover, oxidative (characterized by decreased MDA and increased SOD levels) and nitrosative (characterized by decreased ONOO- levels) damage were limited in these groups. Compared to MI-control rats, most marked change was seen in the nNOS labelling in the nebivolol treated groups. The decrease in iNOS labelling was also prominent in these groups too. CONCLUSIONS: NOS mediated mechanisms of nebivolol can be summarized as: 1) diminishing iNOS expression together with restoration of MI induced eNOS activation both in vascular bed and myocytes at the acute period of MI, and 2) prevention of deterioration in nNOS expression in myocardial cells at the sub-acute period of MI.

Effects of hyperbaric oxygen therapy on biochemical and histological parameters of muscle groups in proximity to the distracted rat tibia.

We investigated the effect of hyperbaric oxygen therapy (HBOT) on rat muscles during tibial distraction osteogenesis (DO) at normal and hyperdistraction rates. Animals in groups 1 and 2 were distracted by 0.5 mm/day and those in groups 3 and 4 by 1 mm/day. Groups 2 and 4 received HBOT during distraction. Group 5 served as control. Superoxide dismutase (SOD; U/g protein), malondialdehyde (nmol/g protein), glutathione (mmol/g protein), and protein levels (g/dl) were determined. SOD was significantly higher in group 2 (4.59 ± 0.97) than in controls (2.19 ± 0.7) (P = 0.0001), and lower in group 4 (3.74 ± 1.70) than in group 2 (P=0.011). Malondialdehyde was significantly higher in group 2 (0.72 ± 0.23) than in controls (0.38 ± 0.10) (P=0.005). Total protein levels were better preserved with HBOT in distracted muscles: group 2 (3.24 ± 0.37) vs. group 1 (1.88 ± 0.60), and group 4 (3.45 ± 0.70) vs. group 3 (2.03 ± 0.75) (both P=0.0001). Numbers of fibres were lower in group 1 (4.88 ± 0.59) than in group 2 (6.07 ± 0.86), and in group 3 (5.13 ± 0.36) than in group 4 (6.14 ± 0.74) (both P=0.001). Numbers of nuclei were higher in group 1 (11.29 ± 2.47) than in group 2 (9.03 ± 1.53) (P=0.04), and in group 3 (12.43 ± 3.32) than in group 4 (9.08 ± 1.58) (P=0.001). Fibres and nuclei with HBOT were similar to those of controls. HBOT decreased the inflammatory cell infiltrate for group 1 (19.8 ± 8.54) vs. group 2 (4.2 ± 2.53) and group 3 (36.54 ± 11.29) vs. group 4 (21.5 ± 9.23) (both P=0.001). HBOT improves the adaptation of distracted muscle by increasing fibres and antioxidants while decreasing inflammation.

Paraoxonase, oxidized low density lipoprotein, monocyte chemoattractant protein-1 and adhesion molecules are associated with macrovascular complications in patients with type 2 diabetes mellitus.

AIM: The aim of this paper was to evaluate the association between blood glucose, oxidative stress, inflammation, endothelial dysfunction and paraoxonase activity as contributors to the accelerated atherosclerosis seen in type 2 diabetic patients. METHODS: Plasma malondialdehyde (MDA), oxidized LDL (oxLDL), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1) levels and paraoxonase-1 (PON1) activity were measured in sixty type 2 diabetic patients, 30 of whom had macrovascular complications, and 30 controls. RESULTS: Diabetics with macrovascular complications had higher levels of MDA, oxLDL, MCP-1, ICAM-1, VCAM-1 than those without, and the difference was significant for all molecules except for ICAM-1. PON1 activity and ApoA1 levels of the controls were significantly higher than that of the patients, while PON1 activity and ApoA1 levels in the patients with macrovascular complications were significantly lower than that in patients without. Ambient plasma glucose concentration showed a significant positive association with plasma MDA, oxLDL, MCP-1, and VCAM, and a significant inverse association with PON1 and ApoA1 in diabetic patients. A significant positive correlation between oxLDL and MDA, a negative correlation between oxLDL and PON1; a significant inverse association between MDA and PON1; a positive correlation between MDA and MCP-1 and VCAM while a negative correlation between PON1 and MCP-1 and VCAM were detected in patients. CONCLUSION: Hyperglycemia might play a significant role in generating increased oxidative stress, and decreased PON1 activity, resulting in elevated oxLDL, MCP-1 and VCAM levels. This might be one of the causal pathogenic factors initiating accelerated atherosclerosis in patients with type 2 diabetes mellitus. The implication of these findings are unclear and therefore further studies are required.