Ilker Tasci

Plasma Apelin and ADMA Levels in Patients with Essential Hypertension

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = −0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

The effect of activated protein C on experimental acute necrotizing pancreatitis

IntroductionAcute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis.Materials and methodForty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured.ResultsAcute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid.Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor--α, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively).ConclusionAPC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.

LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia

Apelin, a relatively newer adipokine with various actions in cardiovascular system, was recently reported to decrease in dyslipidemia. The present study addresses whether plasma apelin increases after hypolipidemic intervention either through therapeutic life style change (TLC) or statin treatment. A total of 134 patients were subjected to treatment with a TLC intervention for 12 weeks. Of these, 116 successfully completed the period, and LDL-cholesterol level decreased to target level (<160 mg/dL) in 54 (46.5%) individuals. The remaining 62 patients were treated with rosuvastatin for 12 weeks, and 56 of them finished the study. Circulating apelin, adiponectin, leptin, TNF-alpha, hsCRP and insulin levels were determined both at baseline and after TLC intervention and statin treatment. There was no significant change in plasma apelin concentration in patients unresponsive to TLC (p=0.110). LDL-cholesterol lowering either through TLC or statin treatment was accompanied by an increase in plasma apelin (p=0.000, p=0.020) and adiponectin (p=0.001, p=0.011). Serum leptin decreased after successful TLC (p=0.042/male, p=0.023/female) but not after statin treatment (p=0.959/male, p=0.134/female). Serum TNF-alpha (p=0.902) and plasma hsCRP (p=0.135) levels remained unchanged after TLC intervention but decreased after statin treatment (p=0.000, p=0.023, respectively). Plasma insulin and homeostasis model assessment scores decreased after TLC (p=0.000 for both) but not rosuvastatin treatment (p=0.865, p=0.722, respectively). In conclusion, independent of the type of treatment, reduction in LDL-cholesterol levels in otherwise healthy people with isolated dyslipidemia results in an increase in plasma apelin concentration. More experiments may show a substantial role for this peptide in the mechanism of atherosclerosis.

Decreased small dense LDL levels in Gilbert's syndrome.

OBJECTIVE To investigate the role of small dense low density lipoprotein cholesterol (sd-LDL-C) in the mechanism of decreased incidence of cardiovascular disease in Gilberts syndrome (GS). DESIGN AND METHODS sd-LDL-C, ox-LDL, and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n=42) and compared to healthy controls (n=52). RESULTS Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls (p<0.001, p<0.001 and p=0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP (r=-0.594, p<0.001; r=-0.249, p=0.016 and r=-0.373, p<0.001 respectively). In addition, sd-LDL-C was positively correlated with ox-LDL (r=0.307, p=0.003). CONCLUSIONS The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.

The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus

AIMS Circulating visfatin levels are altered in insulin resistant states. We evaluated the effects of two insulin-sensitizing hypoglycemic agents on plasma visfatin and adiponectin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM). METHODS Forty-four patients with T2DM were randomized to treatment either with pioglitazone (15-45mg/day) or metformin (1000-2000mg/day). Plasma visfatin and adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) scores were determined at baseline and at 12th week of treatment. RESULTS By the end of the 12th week, fasting plasma glucose, HbA1c, HOMA-IR scores and waist circumferences improved equally in both treatment arms. HDL cholesterol and adiponectin levels increased only in the pioglitazone group (p=0.01 and p=0.003, respectively). On the other hand, metformin treatment had additional regulatory effects on BMI, blood pressure and total and LDL-cholesterol levels (p=0.002, p=0.01, p=0.004, p=0.001 and p<0.001, respectively). Neither pioglitazone nor metformin displayed a significant effect on circulating visfatin concentration. CONCLUSIONS Despite improvements in insulin sensitivity and glycemic regulation, either pioglitazone or metformin treatment did not result in any effect on blood visfatin levels in patients with treatment naïve T2DM.

Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: A link to protection against atherosclerosis?

OBJECTIVE To investigate the role of CD40 ligand and P-selectin in the mechanism of decreased incidence of cardiovascular disease in Gilberts syndrome (GS). DESIGN AND METHODS The soluble forms of CD40 ligand (sCD40L) and P-selectin (sP-selectin), and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n=25) and compared to healthy controls (n=53). RESULTS sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33+/-0.27 vs 0.71+/-0.37 ng/mL, p<0.001 and 0.51+/-0.45 vs 1.16+/-1.31 mg/L, p=0.046, respectively). Both sCD40L and hs-CRP were negatively correlated with total bilirubin (r=-0.5, p<0.001 and r=-0.34, p=0.002, respectively). sP-selectin levels were lower in GS when compared to the controls but the difference did not reach statistical significance (p=0.052). No correlation was found between the plasma levels of sCD40L, sP-selectin and hs-CRP. CONCLUSION These novel findings suggest that reduced sCD40L and hs-CRP concentrations may have a role in the mechanism of protection against atherosclerosis in GS.

Maprotiline induced weight gain in depressive disorder: changes in circulating ghrelin and adiponectin levels and insulin sensitivity.

Agents such as clozapine, olanzapine and mirtazapine frequently trigger an increase in body weight. Though the mechanisms have not been thoroughly clarified, recent studies indicate a role for ghrelin in regulation of appetite and weight gain. We investigated the relation of maprotiline induced weight gain to serum ghrelin and adiponectin levels, as well as insulin resistance in lean subjects with depressive disorder. A total of 40 male lean subjects with depressive disorder were treated with maprotiline (150 mg/day) for 30-days. Clinical data, fasting plasma glucose, lipids, insulin levels, serum ghrelin and adiponectin concentrations were determined before and after treatment. Insulin resistance was estimated using the homeostasis model assessment (HOMA) formula. After 30 days of treatment with maprotiline, mean body mass index increased significantly. Blood ghrelin and insulin levels and HOMA indexes increased, and adiponectin concentration decreased (p<0.001, for all) after the treatment period. Changes in ghrelin levels correlated neither of the parameters tested; whereas decrease in plasma adiponectin was associated with an increase in BMI (r=-0.671, p<0.001). In conclusion, the results indicate that treatment of lean patients with depressive disorder with maprotiline results in an increase in serum ghrelin and reduction in adiponectin levels. Weight gain due to maprotiline treatment may be related to its negative effects on the metabolic variables.

Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell activation.

Objectives: Activation of pancreatic stellate cells (PSCs) is a key event in pancreatic fibrosis. Xanthine oxidase-derived free radicals are involved in the mechanism of chronic pancreatitis (CP). We here searched the in vivo effects of allopurinol on PSC activation and its relation to tissue oxidative stress and histological findings in rat CP. Methods: Rat CP was induced with intraductal trinitrobenzene sulfonic acid in groups 1 (n = 16) and 2 (n = 10). Group 3 (n = 10) received intraductal saline. Four weeks after induction, group 1 received allopurinol (200 mg/kg, SC), and groups 2 and 3 received saline. After 4 weeks, oxidative stress parameters, histological evaluation, and immunostaining for α-smooth muscle actin (+) PSCs were performed in the pancreata. Results: Oxidative stress parameters improved significantly in group 1 compared with groups 2 and 3. Collagen deposition and lobular/sublobular atrophy were significantly lower in group 1 than in group 2. α-smooth muscle actin (+) PSCs counts in group 1 were significantly lower than in group 2, and were in correlation with the degree of fibrosis and atrophy. Conclusions: Allopurinol inhibits PSC activation in vivo. Pancreatic fibrosis can be prevented, at least in part, by antioxidant treatment through xanthine oxidase metabolism. Long-term use of allopurinol and its analogs may be considered in clinical trials with CP.

The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia.

Objective  There is controversy about the effects of statins on insulin resistance and plasma adiponectin. The aim of this study was to investigate the effects of fluvastatin treatment on these parameters in a group of dyslipidaemic patients who had no confounding factors for insulin resistance or alterations in plasma adiponectin.

The effect of combination therapy of hyperbaric oxygen, meropenem, and selective nitric oxide synthase inhibitor in experimental acute pancreatitis.

Despite the new diagnostic and therapeutic advancements, acute pancreatitis has still high rate of morbidity and mortality. We aimed to evaluate the effects of hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT), and meropenem (MER) therapy in an experimental rat model of acute necrotizing pancreatitis. Rats were randomly divided into 8 groups, and acute pancreatitis was induced in all groups except group 1. Treatment protocols were saline for group 2, SMT for group 3, SMT + MER for group 4, SMT + HBO for group 5, HBO for group 6, HBO + MER for group 7, and MER for group 8. All surviving animals were killed 48 hours after the induction of pancreatitis, and specimens were collected. Oxidative stress parameters, histopathologic scores and amylase levels were better in treatment groups than in the positive control group (group 2). The most favorable results were obtained in HBO treatment groups, especially in HBO + MER group (group 7). Our results indicate that adding HBO therapy to the antibiotic therapy will decrease oxidative stress parameters, serum amylase levels, and histopathological score. We suggest that adding the HBO therapy as an adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield improvement in the morbidity and mortality of the disease.