Trimetazidine significantly reduces cerulein-induced pancreatic apoptosis.

OBJECTIVE: Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are still very limited. We aimed to investigate the efficacy of trimetazidine on cerulein-induced pancreatic apoptosis and histopathological and biochemistrical consequences of acute pancreatitis. METHODS: Thirty-two Wistar albino rats were randomized into four groups (group 1: control group; group 2: acute pancreatitis group; group 3: acute pancreatitis and trimetazidine treatment group; group 4: placebo group). Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 µg/kg) four times at one-hour intervals. Trimetazidine was prepared in suspension form. In group 3, after gas anesthesia, trimetazidine was administrated to rats via a catheter. Serum interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, amylase, lipase and leukocyte levels, pancreatic apoptotic status and pancreatic Schoenberg scores were determined for all groups. Results are given as the mean ± SD. A value of P<0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses. RESULTS: In the acute pancreatitis group IL-1ß, amylase, lipase and leukocyte levels were elevated and pancreatic histopathological evaluation revealed a diagnosis of acute pancreatitis IL-1ß amylase and lipase levels and pancreatic inflammation were decreased significantly in the trimetazidine group (P<0.01). White blood cell counts and TNF-α concentrations for the trimetazidine group and the acute pancreatitis group were not significantly different. Trimetazidine significantly reduced apoptosis in pancreatic tissues and Schoenberg scores were also significantly reduced (P<0.05). CONCLUSION: In this study, we showed that trimetazidine treatment significantly decreases the levels of IL-1ß, amylase and lipase reduces pancreatic apoptosis and ameliorates the histopathological findings of cerulein-induced acute pancreatitis. Trimetazidine could be a new therapeutic option in the early treatment of acute pancreatitis.

Comparison of 4 % icodextrin and omega 3 Fatty acids in prevention of peritoneal adhesions.

Postoperative peritoneal adhesions are major concerns in abdominal surgery. In this experimental study, the effects of 4 % icodextrin and omega-3 fatty acids (ω-3 FA) on prevention of postoperative peritoneal adhesions were evaluated. Twenty-four Wistar albino rats were divided into three groups. After laparotomy, serosal abrasion was carried out by cecal brushing. Intraperitoneally 3 cm(3) 0.9 % NaCl, 3 cm(3) 4 % icodextrin, and 200 mg/kg ω-3 FAs for each group were applied, and then the abdomen was closed. All subjects sacrificed 10 days postoperatively. Macroscopic and histopathological cellular reactions as a function of giant cell, lymphocyte/plasmocyte, neutrophil, histiocyte, intracellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) were assessed and hydroxyproline levels were measured in all three groups and compared using Kruskal-Wallis and ANOVA tests when appropriate. Macroscopically, both ω-3 FAs and 4 % icodextrin reduced adhesion formation but the difference was not statistically significant (P = 0.253). Histopathological examination revealed that there was no statistical significance in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM-1, and PECAM-1 scores; however, both ω-3 FAs and 4 % icodextrin were found to be prone to reduce fibrosis (P = 0.047), whereas in the ω-3 FA group, histiocytic reaction was significantly increased (P = 0.001), and hydroxyproline levels were significantly lower than other groups (P = 0.044). In this study, ω-3 FAs were found to be superior to 4 % icodextrin with the lower hydroxyproline level and greater histiocytic reaction. Considering these results, ω-3 FAs can be a promising agent in the prevention of adhesion formation.

Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats.

AIM: Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. MATERIALS AND METHODS: Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1ß and the leukocyte count. RESULTS: When the results of serum amylase, lipase, TNF-α and IL-1ß levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). CONCLUSION: In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

Folate and homocysteine metabolisms and their roles in the biochemical basis of neuropsychiatry.

The term 'one-carbon metabolism' is commonly used to describe 3 separate metabolic processes: folate metabolism, the homocysteine remethylation cycle, and the transsulfuration pathway. Folate metabolism concerns the biochemical reactions in which endogenous and exogenous one-carbon units are transferred to tetrahydrofolates. The remethylation cycle is used for the synthesis of methionine from homocysteine with one-carbon units that come from folate. This methionine is thenfused for the synthesis of S-adenosyl methionine, which is a general donor of methyl groups for many biochemical reactions in the human body. In the transsulfuration pathway, some amino acids and polypeptides, such as cystathionine, cysteine, and glutathione, are synthesized from homocysteine. The kinetics of the enzymes in this pathway are regulated by the substrates of the remethylation cycle. The methylation process has been thought to have an important role in the biochemical basis of neuropsychiatry. An elevated homocysteine level is the most important marker of folate and vitamin B12 deficiencies, and also the most reliable biochemical sign of functional insufficiency. Some neurological and neuropsychiatric diseases, such as psychosis, Alzheimer's disease, and autism, have been found to be related to disorders of one-carbon metabolism. This review aims to summarize both one-carbon metabolism and its relationships with neuropsychiatric disorders.

Can serum fetuin-A be regarded as an inflammatory marker among patients with familial Mediterranean fever?

BACKGROUND/AIM: Familial Mediterranean fever (FMF), the most frequent periodic fever syndrome, is an autosomal recessive inherited disease that predominantly affects eastern Mediterranean populations. Fetuin-A is a well known negative acute-phase protein. Studies of this glycoprotein as a marker of inflammation in FMF are limited. We have investigated the relationship between serum levels of fetuin-A and inflammatory markers in patients with FMF before, during, and after FMF attacks. METHODS: Sixty-seven patients with FMF were enrolled in this study. Serum fetuin-A, seruloplasmin, fibrinogen, C reactive protein (CRP), white blood cell count (WBC), calcium, and erythrocyte sedimentation rate (ESR) were measured three times: during the attack-free period, 12 h after FMF attacks, and 7 days after FMF attacks. Plasma fetuin-A concentration was measured by use of an enzyme-linked immunoassay (ELISA) kit. Correlations and differentiation between the serum fetuin-A and other inflammatory markers in patients with FMF were investigated by use of the paired-samples T test and the Pearson correlation test (p < 0.01). RESULTS: Serum fetuin-A levels of all FMF patients in the attack period were significantly lower than in the attack-free period (p < 0.001). In contrast, serum seruloplasmin (p < 0.05), fibrinogen (p < 0.001), CRP (p < 0.05), WBC (p < 0.05), and ESR (p < 0.05) were all significantly higher than in the attack-free period. Plasma fetuin-A is significantly and inversely highly correlated with the other inflammatory markers. CONCLUSION: Fetuin-A might be a novel indicator of disease activity in patients with FMF and could be used as an adjunctive marker for differentiation of FMF attacks. The negative correlation between serum fetuin-A and other inflammatory markers may also be indicative of inflammation-dependent downregulation of fetuin-A expression in FMF patients.

Effects of levobupivacaine on wound healing.

BACKGROUND: Local anesthetic infiltration along the incision may be used to provide surgical anesthesia or postoperative analgesia. However, the effect of local anesthetics on wound healing remains controversial. In this investigation, we evaluated the effects of levobupivacaine on wound healing. METHODS: Sixty Wistar albino female rats weighing 230±20 g were included, with 10 rats in each group: group early c (early control): 3 mL isotonic saline; group early l1.25 (early levobupivacaine 1.25): 1.25 mg/kg per 3 mL levobupivacaine; group early l2.5 (early levobupivacaine 2.5): 2.5 mg/kg per 3 mL levobupivacaine; group late c (late control): 3 mL isotonic saline; group late l1.25 (late levobupivacaine 1.25): 1.25 mg/kg per 3 mL levobupivacaine; and group late l2.5 (late levobupivacaine 2.5): 2.5 mg/kg per 3 mL levobupivacaine. Rats in groups early c to early l2.5 were euthanized on the 8th day. Rats in groups late c to late l2.5 were euthanized on the 21st day. Wound tension strength, tissue hydroxyproline, and fibrotic index levels of the tissue samples from the early c and early l2.5 and late c and late l2.5 groups, respectively, on the 8th and 21st days were examined. RESULTS: Levobupivacaine decreased wound tension strength on the 8th day, especially a 2.5 mg/kg dose (P<0.001), and increased it on the 21st day (P<0.001). It also increased the inflammatory response (P<0.001) and collagen synthesis (8th day, P=0.109; 21st day, P=0.103) on both the 8th and 21st days. CONCLUSIONS: While levobupivacaine had a positive effect on wound healing during the early period, negative effects were observed thereafter. Additional studies at the molecular level are necessary to determine the cause of these apparently opposite effects.

Prolidase enzyme activity in varicose venous walls related to sperm count in patients with varicocele.

OBJECTIVES: To investigate peripheral, seminal and varicose venous wall prolidase enzyme activities and their relationships between sperm parameters in patients with varicocele. DESIGN AND METHODS: Prolidase enzyme activities were determined in blood, seminal fluid and varicose vein walls in patients with grade 3 varicocele. Sperm parameters were also measured and the relationships between prolidase enzyme and sperm parameters were assessed by statistical correlation analysis. RESULTS: There was a significant and negative correlation between sperm counts and varicose venous wall prolidase enzyme activities (r = -0.618, p < 0.001) and a positive significant correlation between sperm counts and seminal fluid prolidase enzyme activities (r = 0.676, p < 0.001). None of the parameters were correlated with sperm motility indices. CONCLUSION: Varicose venous wall prolidase enzyme activity could be an important factor in progression of azoospermia and infertility in patients with varicocele.

Effects of hemoperitoneum on wound healing and fibrinolytic activity in colonic anastomosis.

BACKGROUND: We aimed to test whether hemoperitoneum has adverse effects on colonic anastomosis healing by increasing fibrinolytic activity. METHODS: After colonic intersection and anastomosis, 20 Wistar Albino rats received intraabdominal injections of either 25 mg/kg blood (10, Group 1) or physiologic saline (10, Group 2). Anastomotic bursting pressures were measured after sacrifice on the fifth day. Following histopathological evaluation of the anastomotic line, hydroxyproline, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and tPA/PAI-1 complex levels were determined in the omentum, lung and anastomotic colon. RESULTS: Mean anastomotic bursting pressures of Groups 1 and 2 were 224.5 mmHg and 254.4 mmHg (p=0.121), and mean hydroxyproline levels were 45.89 and 65.959 mg/g protein, respectively (p=0.257). Histopathology was insignificant. There was a significant difference between groups in omental tPA levels (0.962 ng/ml and 0.27 ng/ml, p=0.041), but not in PAI-1 and tPA/PAI-1. Anastomotic line and lung levels of tPA, PAI-1 and tPA/PAI-1 complex were not significantly different between groups. The relation between anastomotic line tPA level and bursting pressure was highly significant in Group 2 (r=0.778; p=0.008). CONCLUSION: In this first study on the effect of hemoperitoneum on colonic anastomosis, we observed no significant effect on anastomotic healing or fibrinolytic activity, except in the omentum. Further studies with different blood volumes and assessment times are needed.

Effects of alpha tocopherol and ascorbic acid on Helicobacter pylori colonization and the severity of gastric inflammation.

BACKGROUND AND AIM: We aimed to evaluate the changes in histopathologic features, concentrations of vitamins C and E in gastric mucosa, and total antioxidant capacity of the body after ingestion of ascorbic acid and alpha tocopherol in patients with Helicobacter pylori. MATERIAL AND METHOD: Patients with H. pylori-positive nonulcer dyspepsia were included in this study. Tissue samples were taken from the lesser and greater curvature in both prepyloric antrum and corpus for histopathologic examination and measurement of vitamins C and E concentrations. Blood samples were obtained for measurement of the total antioxidant capacity of the body. The patients were given vitamin C 500 mg BID and vitamin E 200 IU BID for 4 weeks orally. At the end of the 4th week, the initial procedures were repeated. Histopathologic examination of the tissue samples were carried out by two pathologists. RESULTS: The mean vitamins C and E concentrations in gastric mucosa at the 4th week were higher than those at the beginning (p = .000 and p = .006, respectively). Mean total antioxidant capacity of the body at the beginning and that at the 4th week were similar (p = .689). H. pylori intensity in the antrum at the beginning was higher than that at the 4th week for both pathologists (p = .007 and p = .039). Neutrophilic activity in the antrum at the beginning was higher than that at the 4th week for both pathologists (p = .000 and p = .025). Neutrophilic activity in the corpus at the beginning was higher than that at the 4th week for pathologist 1 (p = .033), and they were similar for pathologist 2 (p = .763). CONCLUSION: The findings that H. pylori intensity and neutrophilic activity decrease through increasing gastric ascorbic acid and alpha tocopherol concentrations suggest that supplementation with vitamins C and E increases the eradication rates via impairing the microenvironment created by the bacteria and facilitating the diffusion of antibiotics into gastric mucosa.

Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance.

OBJECTIVE: To investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay. RESULTS: HOMA-IR, apelin and visfatin levels (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels. CONCLUSION: Based on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.

Diagnostic value of resistin and visfatin, in comparison with C-reactive protein, procalcitonin and interleukin-6 in neonatal sepsis.

AIM: The aim of this study was to evaluate the predictive value of resistin and visfatin in neonatal sepsis, and to compare these adipocytokines with C-reactive protein (CRP), procalcitonin and interleukin 6 (IL-6). DONORS AND METHODS: A total of 62 term or near term infants with sepsis proven by positivity of blood culture, and 43 healthy infants were included in this study. RESULTS: There were no statistically significant differences between the two groups as regards birthweight and gestational age. White blood cell count (p= 0.039), CRP levels (p=0.01), procalcitonin levels (p=0.01), IL-6 levels (p= 0.01), visfatin levels (p=0.01) and resistin levels (p=0.01) were significantly higher in septic infants. There was a positive correlation between visfatin, resistin and other markers (WBC, CRP, procalcitonin and IL-6). A cut-off value of 10 ng/mL for visfatin, showed 92% sensitivity and 94% specificity, and a cut-off value of 8 ng/mL for resistin showed 93% sensitivity and 95% specificity for neonatal sepsis. CONCLUSION: In the light of these results, visfatin and resistin can be used as a diagnostic marker similar to CRP, procalcitonin and IL-6 in neonatal sepsis. Further studies are needed to better understand the role and predictive value of these molecules in neonatal sepsis.

New adipocytokines (vaspin, apelin, visfatin, adiponectin) levels in children treated with valproic acid.

AIM: To investigate the relationship between the newly discovered adipocytokines and increasing body weight (paralleled by increased insulin resistance), and antiepileptic drug therapy with valproic acid (VPA). DESIGN AND METHODS: 44 children with idiopathic, generalized epilepsy treated with valproic acid (VPA), and 40 control group children were included in this study. RESULTS: Both the VPA-treated group and the control group showed no significant difference in terms of age, total cholesterol and LDL-cholesterol. Subjects in the VPA group had significantly higher BMI-SDS than control subjects (2.3±0.15 vs -0.04±0.8, p<0.001). HOMA-IR, apelin and visfatin levels were significantly increased (4.95±2.07 vs 1.46 vs 0.6, p<0.001; 2.21±1.14 vs 0.57±0.15, p<0.001; 31±12 vs 18.4±10.4, p<0.001; respectively), and adiponectin levels were significantly lower in the VPA group (2.02±1.03 vs 12.4±6.1, p<0.001). Triglyceride levels were significantly increased (126±70 vs 80±40 mg/dL, p=0.001), and HDL-cholesterol levels were significantly lower in the VPA group. Vaspin levels were higher in the VPA group than the control group, but the difference was not significant. CONCLUSION: Based on the findings of this study, apelin, visfatin and adiponectin levels may be considered as potential regulators of glucose and fat metabolism during valproic acid therapy.

Hydroxyproline levels in nasal polyps.

The aim of this study was to evaluate hydroxyproline levels in nasal specimens from patients with nasal polyps, and to examine hydroxyproline levels after nasal steroid spray and oral steroid treatments. This study was performed on 41 patients. The subjects were divided into four groups: no medication group (group A, n 11), oral methylprednisolone group (group B, n 8), topical steroid spray group (group C, n 8) and control group (group D, n 14). Nasal polyp samples were collected endoscopically. Healthy subjects were studied as a control group, and their nasal samples were taken during turbine reduction surgery. All samples were analyzed using the immunocytochemistry method. Hydroxyproline levels were investigated and compared with the control group. Mean hydroxyproline levels in groups A-D were 98.48, 24.20, 8.97 and 4.52, respectively. The hydroxyproline levels were significantly higher in group A compared with that of group D. The treatment that revealed significant decreases in hydroxyproline levels was group C. Although there was also a noticeable reduction in group B, there were no statistically significant differences between group B and group A. Our study revealed a significant correlation between nasal polyp and hydroxyproline levels. The hydroxyproline levels were significantly higher in nasal polyps. Both oral and topical steroid treatments decrease hydroxyproline levels in nasal polyps. Thus, in theory, steroid treatment can directly decrease hydroxyproline levels by inhibiting proline hydroxylase and indirectly by lowering the inflammatory process.

Renal zinc clearance/glomerular filtration rate ratio as an indicator of marginal zinc deficiency associated with iron deficiency in childhood.

OBJECTIVE: To evaluate the usefulness of renal zinc clearance/glomerular filtration rate ratio (R(ClZn)/GFR) as an indicator of marginal zinc deficiency that is generally associated with iron deficiency in childhood. METHODS: Zinc status was evaluated in 36 iron-deficient children (22 boys and 14 girls) who ranged in age from 1 to 10 years using serum zinc concentration and U(Zn/Cr) and R(ClZn)/GFR ratios. The results were compared with the zinc status of 36 similar-aged healthy children (24 boys and 12 girls). RESULTS: Serum zinc concentrations were 96.72 +/- 2.13 microg/dL and 93.93 +/- 1.95 microg/dL in iron-deficient and healthy subjects, respectively (p > 0.05). U(Zn/Cr) ratios were 0.54 +/- 0.04 microg/mg and 0.88 +/- 0.04 microg/mg (p < 0.0001); R(ClZn)/GFR ratios were 2.27 x 10(-3) +/- 0.20 and 3.32 x 10(-3) +/- 0.20 (p < 0.001) in iron-deficient and healthy subjects, respectively. Individual values of R(ClZn)/GFR and U(Zn/Cr) ratios correlated with hemoglobin (Hb) concentrations (r = 0.34, p < 0.01 and r = 0.26, p < 0.05). Data grouped according to the ranges of Hb concentrations and R(ClZn)/GFR and U(Zn/Cr) ratios fit the following equations: The statistically significant difference in U(Zn/Cr) and R(ClZn)/GFR ratios between groups indicates decreased urinary estimation of marginal zinc deficiency, whereas no change was observed in serum zinc concentrations. According to the regression equation, it can be postulated that the R(ClZn)/GFR ratio is a linear function of Hb concentration and the U(Zn/Cr) ratio. CONCLUSION: R(ClZn)/GFR ratio was a reliable indicator for reduction in urinary zinc excretion; it estimated the marginal zinc deficiency associated with iron deficiency. The R(ClZn)/GFR ratio can be calculated using one sample of blood and urine; thus it could serve as an alternative indicator of marginal zinc deficiency, especially in routine health care.

Elevated plasma levels of apelin in children with type 1 diabetes mellitus.

BACKGROUND: Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. OBJECTIVE: To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. METHODS: Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. RESULTS: Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. CONCLUSIONS: Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.