Gonul Simsek

Changes in Leptin, Plasminogen Activator Factor and Oxidative Stress in Morbidly Obese Patients following Open and Laparoscopic Swedish Adjustable Gastric Banding

Background: Oxidative stress is increased in obesity, leading to endothelial dysfunction, atherogenesis, and platelet aggregation. The purpose of this study was to determine the effects of weight loss after bariatric surgery on serum lipids, malondialdehyde (MDA, a marker of oxidative stress), oxidized low-density lipoprotein (oxLDL, which is increased in obesity and causes endothelial dysfunction), paraoxonase (PON-1, which inhibits lipid peroxidation), leptin and plasminogen activator inhibitor type-1 (PAI-1, which contributes to a thrombotic state). Methods: 40 morbidly obese patients had insertion of a Swedish adjustable gastric band (SAGB). A lipid profile, MDA, oxLDL, PON-1, leptin and PAI-1 levels were drawn before and 6 months after the operation. 20 patients underwent open (Group 1) and 20 laparoscopic (Group 2) SAGB, to compare the systemic inflammatory response of the two approaches. Results: Patient demographics, indications for surgery, and postoperative results were no different between the groups. Postoperative BMI and concentrations of lipid, MDA, oxLDL, leptin and PAI-1 decreased significantly in both groups. PON-1 activity increased and was negatively correlated with BMI (r=-0.618, P< 0.01), MDA (r=-0.735, P<0.001), oxLDL (r=-0.701, P< 0.01), leptin (r=-0.626, P<0.01) and PAI-1 (r=-0.461, P<0.05). There was a correlation between BMI and MDA (r=0.790, P <0.001), and also leptin (r=0.900, P<0.001) and PAI-1 (r=0.888, P=0.001). There was no correlation between BMI and oxLDL. Conclusion: These findings support the hypothesis that in morbid obesity, weight loss after surgery has positive effects on fibrinolytic function, oxidative stress and antioxidant activity. Both operative approaches had similar effects in this study.

Oxidative stress in white coat hypertension; role of paraoxonase.

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.

Effects of lipopolysaccharide on the radiation-induced changes in the blood-brain barrier and the astrocytes.

The use of radiation to improve the efficacy of chemotherapy on malignant brain tumors is also known to cause side effects on vascular endothelial cells and astrocytes in normal parts of the brain. We investigated the effects of lipopolysaccharide (LPS) on the functional and structural properties of blood-brain barrier (BBB) and the activity of astrocytes during whole-brain irradiation in rats. The permeability of the BBB to Evans blue (EB) dye significantly increased in the cerebral cortex, diencephalon and cerebellum regions of rats exposed to irradiation (P<0.01). In contrast, the BBB permeability in irradiated rats was significantly reduced by LPS (P<0.05). Tumor necrosis factor-alpha (TNF-alpha) levels were increased following LPS, irradiation and irradiation plus LPS (P<0.05, P<0.01). Irradiated brain vessels showed a considerable loss of staining intensity of tight junction proteins Zonula occludens-1 (ZO-1) and occludin. Staining for Zonula occludens-1 and occludin was intensive in animals treated with LPS and irradiation plus LPS. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in very few astrocytes of irradiated brains. However, this staining showed an increased positive intensity in the brain sections of LPS-treated as well as of irradiation plus LPS-treated animals. These results indicate that LPS reduces the passage of exogenous vascular tracer EB-binding albumin into the brain, at least partly, by increasing the expression of tight junction proteins and GFAP, following the irradiation. We suggest that irradiation may affect paracellular permeability through disruption of tight junction proteins, Zonula occludens-1 and occludin, and LPS could provide beneficial effects on the BBB integrity and the astrocytes against irradiation damage.

CALCIUM, MAGNESIUM, AND ZINC STATUS IN EXPERIMENTAL HYPERTHYROIDISM

In this study, experimental hyperthyroidism was established and used to investigate possible alterations in the calcium (Ca), magnesium (Mg), and zinc (Zn) homeostasis by assessing their concentrations in plasma and erythrocytes.In the L-thyroxine-induced hyperthyroidism condition, the experimental animals show a significant decrease in erythrocyte Ca, Mg, and Zn concentrations, and a significant decrease in plasma Mg concentration. Significant positive correlations were found for Mg and Zn both in plasma and in erythrocytes.The results suggest that the homeostasis of Ca, Mg, and Zn is altered during experimental hyperthyroidism.

Endothelium and angiogenesis in white coat hypertension.

Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. The aim of this study was to compare the risk conferred by white coat hypertension (WCH) vs sustained hypertension in the development of the endothelial dysfunction and abnormal angiogenesis by evaluating nitric oxide (NO=NO2+NO3), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and E-selectin levels in plasma. The study group included 102 subjects, 34 with WCH (17 male and 17 female patients) aged 49±11 years, 34 sustained hypertensives (HT) (15 male and 19 female patients) aged 47±11 years and 34 normotensive control subjects (NT) (16 male and 18 female patients) aged 48±10 years. WCH was defined as clinical hypertension and daytime ambulatory blood pressure less than 135/85 mmHg. The subjects were matched for age, gender, body mass index and the patients with smoking habit, dyslipidaemia, and diabetes mellitus were excluded from the study. The NO, ET-1, VEGF and E-selectin levels were analysed by ELISA technique. The WCH subjects had significantly higher levels of NO than the HT (41.68±2.23 vs 32.18±2.68 μmol/l; P<0.001) and significantly lower values than the NT (48.24±4.29 μmol/l; P<0.001). ET-1 levels of the WCH group were significantly higher than the NT (8.10±0.92 vs 5.95±0.26 ng/ml; P<0.001) and significantly lower than the HT (11.46±0.59 ng/ml; P<0.001). Considering with VEGF, the WCH group had significantly higher levels than the NT (195.88±11.84 vs 146.26±18.67 pg/ml; P<0.001), but the difference from the HT group was not significant (203.35±7.48 pg/ml; P=0.062). E-selectin in the WCH group was significantly lower than the HT (4.77±0.52 vs 8.49±2.85; P<0.001), but the difference from the NT group was not significant (3.86±0.67; P=0.077). Our data demonstrate that WCH is associated with endothelial dysfunction and abnormal angiogenesis. The degree of these changes is not as severe as observed in hypertensive population.

Assessment of low-density lipoprotein oxidation, paraoxonase activity, and arterial distensibility in epileptic children who were treated with anti-epileptic drugs

OBJECTIVE Studies show that anti-epileptic drugs increase oxidative stress. Thus, low-density lipoprotein oxidation increases and atherogenesis is induced. Paraoxonase-associated high-density lipoprotein protects low-density lipoprotein and high-density lipoprotein oxidation. The effects of anti-epileptic drugs on paraoxonase activity has not been investigated yet. The aim of this study is to investigate the effect of anti-epileptic drugs on paraoxonase activity, lipid profiles, folat, vitamin B12, homocysteine, thyroid hormones, apolipoprotein A-1, total anti-oxidant capacity, malondialdehyd, nitric oxide, and oxidised low-density lipoprotein. The association with carotid-femoral pulse wave velocity and current biochemical parameters had been searched for assessing the effects of anti-epileptic drugs on the vascular system. PATIENTS AND METHODS We recruited 59 epileptic patients treated with anti-epileptic drugs and 23 controls (group IV) at least 6 months ago. The epileptic group was divided into three groups by receiving anti-epileptic drugs as follows: group I: carbamazepine, group II: valproic acid, and group III: carbamazepine and valproic acid. Arterial distensibility was assessed with the Complior device. RESULTS There was no difference between the current biochemical parameters in epileptic children. Serum-free T4 was decreased, when compared with group IV. Thyroid-stimulating hormone was increased in group II, compared with group IV. The carotid-femoral pulse wave velocity was increased in group III, compared with group IV. The carotid-femoral pulse wave velocity was correlated with thyroid-stimulating hormone and valproic acid levels. CONCLUSIONS Anti-epileptic drugs may induce atherogenesis by affecting the thyroid hormones. According to the current data, the effects of thyroid hormones on vascular system may be independent of other biochemical markers. Epileptic patients using anti-epileptic drugs must be followed closely for arterial stiffness, and also for the development and progression of atherosclerosis.

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.

The role of feed regulating peptides on weight loss in patients with pulmonary tuberculosis.

PURPOSE Malnutrition is a prominent feature of tuberculosis (TB). The aim of our study was to explore the function of plasma regulatory proteins in pulmonary TB and to investigate the relationship between these parameters and loss of body weight. METHODS Plasma levels of fasting insulin, leptin, ghrelin, adiponectin and orexin-A were measured in 23 pulmonary TB patients, 39 patients with pulmonary sarcoidosis, 22 patients with different diffuse interstitial lung diseases and 21 healthy patients serving as controls. RESULT Plasma leptin (p<0.001) and orexin-A (p<0.01) levels were significantly decreased in TB patients compared with those of the other study subjects. TB patients also had higher levels of plasma ghrelin compared with those of the other study subjects, while sarcoidosis patients had higher plasma adiponectin levels than the other study subjects. Glucose levels were similar in all groups, yet, insulin and Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) levels were significantly higher in the TB group compared to the other study groups. There was no correlation between leptin, ghrelin, adiponectin and orexin-A and other parameters. CONCLUSIONS These data suggest that leptin and orexin-A levels have effects on weight loss in patients with pulmonary tuberculosis. Particularly, leptin may play a role in the early immune response to pulmonary TB and prolonged inflammation may further suppress leptin production. Measurement of HOMA-IR can indeed be used as a marker for the risk of activated TB. Further clinical studies are needed to better understand the role of feed regulating proteins in pulmonary tuberculosis.

The relationship between circulating irisin, retinol binding protein-4, adiponectin and inflammatory mediators in patients with metabolic syndrome

OBJECTIVE We wanted to investigate whether there is a relationship between circulating irisin, retinol binding protein-4 (RBP-4), adiponectin and proinflammatory mediators implicated in the development of insulin resistance (IR) in metabolic syndrome (MetS). SUBJECTS AND METHODS In 180 individuals, including controls and patients with MetS, we measured fasting plasma insulin, high sensitivity C-reactive protein (hsCRP), pentraxin-3 (PTX-3), interleukin-33 (IL-33), irisin, RBP-4, and adiponectin using ELISA kits. RESULTS While fasting plasma hsCRP, PTX-3, IL-33, irisin, RBP-4 concentrations were higher, adiponectin levels were lower in patients with MetS than in controls. A correlation analysis revealed that plasma irisin levels were positively associated with MetS components such as waist circumference and waist-hip ratio, low density lipoprotein (LDL) and markers of systemic inflammation such as PTX-3, hsCRP, uric acid, and RBP-4. Adiponectin levels were negatively associated with waist circumference, waist-hip ratio, PTX-3 and LDL. CONCLUSIONS Although the precise mechanisms are still unclear, irisin, RBP-4, adiponectin and PTX-3 are hallmarks of the MetS, which is related to low-grade inflammation. It is conceivable that irisin and adiponectin might contribute to the development of MetS and may also represent novel MetS components. Future clinical studies are needed to confirm and extend these data.

Association of Plasma Pentraxin-3 Levels with Retinopathy and Systemic Factors in Diabetic Patients

BACKGROUND Diabetic retinopathy (DR) is mainly caused by metabolic factors, vascular inflammation, and endothelial dysfunction. We aimed to evaluate the relationship of DR with inflammatory and biochemical alterations in type 2 diabetics. METHODS A total of 89 diabetic patients with retinopathy [(DR (+) (n = 30)], without retinopathy [(DR (-) (n = 32)], and 27 control subjects were involved in the study. Demographic properties, biochemical values, ophtalmologic evaluation, C-reactive protein (CRP), and pentraxin-3 (PTX-3) levels were recorded. RESULTS There was significant difference between controls, DR (-) and DR (+) groups with regard to serum PTX-3 levels. Control group had the lowest and DR (+) group revealed the highest PTX-3 levels. Severity of retinopathy was not related with CRP or PTX-3 levels. Duration of diabetes was longer, systolic blood pressure (SBP) and urinary albumin-creatinine ratio (UACR) were significantly higher in DR (+) subjects than DR (-) subjects. Multivariate analysis revealed that PTX-3 level and SBP were the variables that had a significant effect on DR (P = 0.002, OR = 1.61, and P = 0.021, OR = 1.06, respectively). CONCLUSIONS Plasma PTX-3 levels may be a valuable predictor of DR-like factors such as duration of diabetes, hypertension, and UACR. Although inflammation has an important role in DR, we think that biomarkers reflecting inflammation is not sufficient to predict development and progression of DR; but follow up with PTX-3 levels along with ophthalmological evaluation may be useful. A single determination may not reflect the variations over time, so repeat measures may provide knowledge if PTX-3 is just a biomarker or has a causal role.