Firdevs Aylak

The effects of chelators on zinc levels in patients with thalassemia major.

Zinc which is an essential element has very important effects on growth and immune system in patients with thalassemia major (TM). The effects of two oral iron chelator agents, desferrioxamine (DFO) and deferiprone (DFP), on zinc levels were investigated in previous studies and they were found to cause zinc deficiency. Zinc level alteration by the new chelator deferasirox (DFX) is not present in the literature. The aim of this study was to examine the effects of different oral chelators on serum and urine zinc levels in TM patients. Zinc levels are compared in the patients who received different chelators: only DFX, combined chelation with DFO plus DFP and the healthy control group. A total of 56 patients with TM were involved in this study: 39 patients received only DFX and 17 patients were given combined treatment DFO+DFP between August 2008 and August 2009. In addition, a control group was established from the healthy population. Blood was taken from all the patients for serum zinc levels and 24hour-urine samples were collected for urine zinc levels. Serum zinc levels were found to be 64.8±14.8μg/dL in DFX group and 66.5±15.1μg/dL in DFO+DFP group. These levels were statistically lower than that in the control group (149±54.3μg/dL) (p<0.05), but there was no statistically difference between the two different chelation groups (p>0.05). The urine zinc levels of DFX and DFO+DFP group were 662.2±428.2μg/day and 1182.3±980.3μg/day respectively (p<0.05). Urinary zinc excretion in the chelation groups (DFX and DFO+DFP) was significantly higher than the control group (395.1±208.9μg/day) (p<0.05). As a conclusion, the new chelation agent, DFX, also leads to zinc deficiency, though its urinary zinc excretion is lower. New studies are required to examine the effects of DFX on zinc extensively. Zinc levels of patients with TM should be followed up regularly and zinc supply should be given at early ages.

The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn

INTRODUCTION Accidental ingestion of caustic substances may cause serious problems in children. Approximately 20% of caustic ingestions result in esophageal stricture formation, resulting from excessive collagen synthesis to the extracellular matrix by fibroblasts. Recent studies showed that a single application of 5-fluorouracil (5-FU) is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods. Using an experimental model, we investigated the efficacy of single-dose 5-FU on stricture formation after caustic esophageal burn. MATERIALS AND METHODS Forty Wistar-Albino rats were divided randomly into 4 equal groups: group 1 (sham-operated group), the esophagus was uninjured and untreated; group 2 (control group), the esophagus was injured and left untreated; group 3 (intraperitoneal treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraperitoneal dose (20 mg/kg) of 5-FU; group 4 (local treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraesophageal application of 5-FU at a concentration of 25 mg/mL. Caustic esophageal burn was produced by instilling 10% NaOH in the distal esophagus. The distal esophagi were harvested at 28 days postoperatively. Histologic sections were assessed by measuring the stenosis index (SI) and histopathologic damage score. Hydroxyproline (HP) levels in the tissues were determined biochemically. RESULTS There were significant reductions in the SI (P < .05), histopathologic damage score (P < .05), and HP level (P < .05) in the intraperitoneal treatment group when compared with the control group. No significant differences in the SI and histopathologic damage score were detected between the control and local treatment groups (P > .05), whereas significant reduction in the HP level was determined between these groups (P < .05). CONCLUSION A single intraperitoneal dose of 5-FU had a preventive effect on stricture formation after caustic esophageal burn. This observation suggests that 5-FU may prevent this undesirable complication in the clinical setting. Clinical studies are now required to verify this form of treatment. Local intraesophageal application of 5-FU immediately after the burn injury was not effective. Further investigations are required to determine the appropriate timing of application of 5-FU at the local site of injury.

Juniperus communis Linn oil decreases oxidative stress and increases antioxidant enzymes in the heart of rats administered a diet rich in cholesterol

It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250–300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant–antioxidant effect in the heart tissue of rats.

Increased neopterin levels and its association with angiographic variables in patients with slow coronary flow: an observational study.

OBJECTIVE Although various inflammatory markers have been studied in patients with slow coronary flow (SCF), serum neopterin levels have not been studied previously. We investigated the serum neopterin and high sensitivity C-reactive protein (hs-CRP) levels and the relationship between neopterin and hs-CRP levels and TIMI flow in patients with SCF. METHODS The study group consisted of 51 patients with SCF. An age and gender matched control group was composed of 40 subjects. Coronary flow rates of all patients and control subjects were documented by Thrombolysis in Myocardial Infarction (TIMI) frame count. We measured serum neopterin and hs-CRP levels at the same time in patients with SCF and control subjects in this cross-sectional observational study. Chi-square, Mann-Whitney U and unpaired t tests, Pearson correlation and linear regression analyses were used for statistical analysis. RESULTS The TIMI frame counts for all coronary arteries and the mean TIMI frame count were significantly higher in the SCF group than controls. Serum neopterin levels were significantly higher among patients with SCF when compared with control group (2.13±1.03 vs. 1.60±0.50 ng/ml; p=0.004). Serum hs-CRP levels were significantly higher among patients with SCF when compared with control group (2.06±1.32 vs. 0.74±0.40 mg/L respectively; p<0.001). There was a significant association of serum neopterin levels (β=0.60, 95% CI: 4.93-9.06, p<0.001) and serum hs-CRP levels (β=0.29, 95%CI: 0.84-4.33, p=0.004) with mean TIMI frame count independent of potential confounders such as age, gender, body mass index, smoking, glucose and cholesterol levels. CONCLUSION We have shown that serum neopterin and hs-CRP levels were significantly elevated in patients with SCF when compared with control subjects. Serum neopterin and hs-CRP levels were correlated with mean TIMI frame count in patients with SCF.

Are there any remarkable effects of prenatal exposure to food colourings on neurobehaviour and learning process in rat offspring

Abstract Objective Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process. Methods We administered ‘no observable adverse effect levels’ (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests. Results Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on ‘latency to locate the visible platform’, which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05). Discussion These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

Impact of micronised purified flavonoid fraction on increased malondialdehyde and decreased metalloproteinase‐2 and metalloproteinase‐9 levels in varicocele: outcome of an experimentally induced varicocele

To analyse the levels of an indirect marker of ROS‐induced lipid peroxidation [i.e. malondialdehyde (MDA)] in both testes and the levels of matrix metalloproteinase‐2 (MMP‐2), matrix metalloproteinase‐9 (MMP‐9) and matrix metalloproteinase inhibitor‐1 (TIMP‐1) in the left testis after induction of varicocele and investigated the impact of micronised purified flavonoid fraction (MPFF) on these markers. Forty‐nine adolescent (6‐week‐old) male Wistar rats were included in this study. The rats were divided into seven groups as follows:Group‐1, control; Group‐2, sham; Group‐3, left varicocele‐induced; Group‐4, varicocele + varicocelectomy + MPFF‐treated (for 4 weeks); Group‐5, varicocele + MPFF‐treated (for 8 weeks); Group‐6, varicocele‐induced and 4 weeks later, MPFF‐treated (for 4 weeks); and Group‐7, varicocele + varicocelectomy. MDA was measured in the tissues of both testes using the thiobarbituric acid reactivity method. The ELISA method was used for the quantification of MMP‐2, MMP‐9 and TIMP‐1 in the left testicular tissue. The levels of MDA were significantly higher in the varicocele group than in the other groups. The MDA levels in the left testicular tissues of Group‐7 were significantly higher than those of Group 4 (P = 0.03). In the varicocele group, the MMP‐2 and MMP‐9 levels decreased, whereas the levels of TIMP‐1 increased. The tissue levels of MMP‐2 in Groups 4, 5 and 7 were significantly higher than those in Group 1 (P < 0.05).

The Effect of Micronized Purified Flavonoid Fraction on the Prevention of Testicular Pathologies in Adolescent Rats with Experimentally Induced Varicocele

PURPOSE We investigated the effect of micronized purified flavonoid fraction on the prevention of testicular pathologies following varicocele induction. MATERIALS AND METHODS A total of 66 adolescent (6-week-old) male Wistar rats were included in study. Rats were divided into 7 groups, including group 1--control, group 2--sham operation, group 3--left varicocele induced, group 4--varicocele induced, varicocelectomy done 4 weeks later and micronized purified flavonoid fraction administered for 4 weeks, group 5--varicocele induced and micronized purified flavonoid fraction administered for 8 weeks, group 6--varicocele induced and beginning 4 weeks later micronized purified flavonoid fraction administered for 4 weeks, and group 7--varicocele induced and varicocelectomy done 4 weeks later. Before sacrifice bilateral real-time testicular microvascular perfusion of all rats was measured using the PeriFlux System 5000 PF 5010 LDPM Unit (Perimed, Järfälla, Sweden). All testes were graded according to the Johnsen scoring system. To assess apoptosis caspase-3 levels were measured. RESULTS Testicular weight in group 3 was markedly decreased and the extent of seminiferous tubular damage was significantly increased compared with the other groups. Bilateral testicular blood flow and the number of apoptotic germ cells were greater in group 3. Significantly higher Johnsen scores and a meaningful decrease in the apoptotic index were detected in groups 4 to 7 compared with group 3. CONCLUSIONS We observed favorable effects of micronized purified flavonoid fraction on the regression of testicular damage secondary to varicocele.

AB0894 The Significance of Urinary Beta-2 Microglobulin Level for Differential Diagnosis of Familial Mediterranean Fever and Acute Appendicitis

Background The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. Objectives The present study aims to investigate the urinary beta-2 microglobulin (U-β2M) level as a potential parameter to identify these two diseases mimicking each other. Methods A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1–1.5mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens urinary Beta-2 Microglobulin, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. Results U-β2M levels were significantly higher in acute appendicitis group compared to FMF group during attack period, FMF group during attack free period, and control groups (p<0.001, p<0.001, and p<0.001 respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF group during attack period, and FMF group during attack free period compared to controls (U-NAG p<0.001, p=0.016, p=0.004, microalbuminuria p<0.001, p<0.001, p<0.001 respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF group during attack period (p=0.004). Conclusions Determination of U-β2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment, and acute appendicitis. However, this finding should be substantiated with other studies. Disclosure of Interest None declared