Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model.

INTRODUCTION: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. METHODS: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. RESULTS: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. CONCLUSIONS: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

Glycosaminoglycan-induced proinflammatory cytokine levels as disease marker in mucopolysaccharidosis.

Recently, it has been shown disturbances in oxidant/antioxidant system and increases in some inflammatory markers in animal studies and in some Mucopolysaccharidoses (MPSs) patients. In this study, we aimed to determine the oxidative stress/antioxidant parameters and pro-inflammatory cytokine levels in the serum of MPS patients, in order to evaluate the possible role of inflammation in these patient groups regarding to accumulated metabolites. MPS I (n = 3), MPS II (n = 8), MPS III (n = 4), MPS IVA (n = 3), MPS VI (n = 3), and VII (n = 1) patients and 20 age-matched healthy subjects were included into the study. There was no statistically significant change in activities of SOD, Catalase, GSH-Px and lipid peroxidation levels in erythrocytes between the MPS patients and healthy controls. While IL-1alpha (p = 0.054), IL-6 (p = 0.008) levels, and chitotriosidase activity (p = 0.003) elevated in MPS3 patients, IL1α (p = 0.006), IL-1ß (p = 0.006), IL-6 (p = 0.006), IFNγ (p = 0.006), and NFκB (p = 0.006) levels increased in MPS-6 patients. Elevated levels of IL-6, IL1α and chitotriosidase activity demonstrated macrophage activation in MPSIII untreated with enzyme replacement. Our study showed for the first time that high levels of IL1α, IL-6, IL1ß and NFκB were present in MPSVI patients, demonstrating the induction of inflammation by dermatan sulphate. The low level of paraoxonase in MPSVI patients may be a good marker for cardiac involvement. Overall, this study provides important insights into the relationship between lysosomal storage of glycosaminoglycan and inflammation in MPS patients. It highlights possible pathways for the increased release of inflammatory molecules and suggests new targets for the development of treatments.

High chitotriosidase and AGE levels in acromegaly: a case-control study.

PURPOSE: Acromegaly is associated with oxidative stress and inflammation parameters. Chitotriosidase (CHITO) is a marker of macrophage activation and plays a pivotal role in the activation of inflammatory and immunological responses. Our study aimed to determine CHITO,YKL-40, advanced glycation end product (AGE), and high-sensitivity C-reactive protein (hsCRP) levels to investigate malondialdehyde (MDA), catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and to evaluate any association of these parameters with carotid intima media thickness (cIMT) in patients with controlled acromegaly. METHODS: Thirty controlled acromegaly patients and 41 age- and sex-matched control cases were studied. We obtained demographic data, hormonal and metabolic parameters, and cIMT. CHITO activity was measured with the fluorometric method of Chamoles et al. YKL-40 and hsCRP levels were measured using ELISA. AGEs were measured based on spectrofluorimetric detection. GSH-Px activity was determined by a colorimetric assay. MDA, SOD, and catalase activities were determined in hemolysis. RESULTS: Higher CHITO, AGE, and hsCRP concentrations were observed in patients with acromegaly compared to controls. SOD levels were non-significantly higher in the acromegaly group, while catalase activities were lower in patients with acromegaly. Correlation analyses of CHITO, AGEs, YKL-40, hsCRP, MDA, catalase, GSH-Px, and SOD with metabolic, anthropometric, and laboratory parameters did not demonstrate any significant correlation (p > 0.05). There was no significant difference between groups with regard to cIMT levels. CONCLUSION: This is the first study investigating CHITO and AGE levels in patients with acromegaly. Serum CHITO, AGE, and hsCRP levels in acromegalic patients were significantly increased. It may be important to evaluate CHITO, AGE, and hsCRP levels in acromegalic patients who are already under cardiometabolic surveillance due to risk of developing cardiovascular disease.

Perspective on pros and cons of microlearning in health education.

Recently, digital technology and digital materials have started to be widely used in education from primary school to college worldwide. Microlearning is one of the innovative teaching techniques that use digital technologies. In this review, benefits and disadvantages of microlearning is discussed. Many studies show that microlearning facilitated learning by dividing into smaller pieces encourages students to study. A wide range of activities might be used in this technique and it can be easily integrated into daily routine, it allows on-demand learning for the students. On the other hand, the success of microlearning techniques is closely related to the personal characteristics of learners, teachers' prone to use digital technology and the external factors such as access to learning materials. Its effectiveness on behavior and outcome which were defined in the third and fourth levels of Kirkpatrick's learning model is still obscure. In the light of the literature, it should be decided which microlearning method will be used for which educational subjects.

A novel marker of systemic inflammation in psoriasis and related comorbidities: chitotriosidase

Background/aim: Chitotriosidase (ChT) is an enzyme secreted by activated macrophages and neutrophils in response to proinflammatory signals. There is growing evidence indicating that ChT activity reflects the systemic inflammatory status. This study aimed to investigate whether serum ChT activity increased in patients with psoriasis and related comorbidities. Materials and methods: This cross-sectional study included 53 (28 with associated comorbidities and 25 without comorbidities) patients with psoriasis and 52 healthy volunteers. All participants underwent laboratory investigations for serum ChT levels, complete blood count, erythrocyte sedimentation rate, C-reactive protein, and serum lipid levels. Results: The patients with psoriasis showed significantly higher levels of ChT activity as compared to the healthy controls (23.5 ± 11.4 vs. 17.5 ± 10.4 µmol/mL/hour; p = 0.015). Additionally, the ChT activity was significantly higher in patients with comorbidities than in those without (p = 0.042). Conclusion: Our data support the pathogenetic role of inflammatory processes induced by macrophage activation in patients with psoriasis and related comorbidities. We believe that high ChT activity in patients with psoriasis may serve as an early prediction of the possible related comorbidities.

The decision-making levels of urine tetrasaccharide for the diagnosis of Pompe disease in the Turkish population.

Background Recently, urinary excretion of the tetrasaccharide 6-α-D-glucopyranosyl-maltotriose (Glc4) has been proposed as a marker for the diagnosis and monitoring of Pompe disease (PD). We aimed to determine the reference intervals and reliable decision-making levels of urine tetrasaccharide concentrations for the diagnosis of infantile- and late-onset Pompe patients in the Turkish population. Methods In this study, nine patients with PD (five of them with late-onset PD [LOPD]) and 226 healthy individuals (aged 0-64 years) were included. Urine Glc4 concentrations were determined using the ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method. Results Our data showed that the urine tetrasaccharide levels decreased with age in healthy individuals (p < 0.001, r = -0.256). It was higher especially during the first year of life compared to that in the elder subjects. The tetrasaccharide level of Pompe patients was higher compared to that of healthy controls of the same age: 99 ± 68 mmol/mol creatinine for infantile onset vs. 4.0 ± 3.0 mmol/mol creatinine for healthy controls of the same age group and 12.1 ± 17.4 mmol/mol creatinine for late onset vs. 1.7±1.2 mmol/mol creatinine for healthy controls of the same age group. Conclusions The results of this study showed that the reference intervals of tetrasaccharide in urine changed over time; therefore, it is critically important to define age-based decision levels for the diagnosis of LOPD.

Propolis prevents inhibition of apoptosis by potassium bromate in CCD 841 human colon cell.

Previously, we demonstrated that biotransformation of propolis by some special strains of Lactobacillus plantarum might decrease the allergenic molecules in propolis. In this study, we aimed to investigate the effect of biotransformation of propolis on its antioxidant effect and its protective effect against potassium bromate-induced cancer in human colon cell line. Propolis samples were treated with different solutions (ethanol, polyethylene glycol, and water), and ultrasonication was applied at 40 Hz (5, 10, and 15 minutes) in order to facilitate solvation of solid samples. Fermentations were performed by L. plantarum strains (ISLG-2, ATCC-8014, and Visbyvac). The phenolic content of propolis was determined with liquid chromatography-mass spectrometry/mass spectrometry (LCMS/MS). The antioxidant activity (antioxidant enzymes, lipid peroxidation) and apoptosis markers (caspase 3,8,9, cytochrome-c, tumour necrosis factor-related apoptosis-inducing ligand-R1 and R2 [TRAIL], and apoptosis protease activating factor-1 [APAF-1] levels) were determined in CCD 841-human colon cell line after induction of oxidative stress by potassium bromate. All propolis samples in different solvents induced apoptosis and 4 biotransformed (by L. plantarum ISL-2 strain and L. plantarum ATCC 8014 strain) propolis samples with low allergenic molecules demonstrated similar inductions of apoptosis in CCD841 cell line. In conclusion, reduction of allergenic molecules in propolis via biotransformation did not change the antioxidant and protective effects of propolis, and it is suggested as a potential therapeutic molecule in prevention of colon cancer caused by oxidative stress for all patients. SIGNIFICANCE OF THE STUDY: This study is the first investigation that shows protective effect of propolis against potassium bromate toxicity by means of decreasing lipid peroxidation and reversing the main molecule levels in intrinsic and extrinsic pathway of apoptosis. Biotransformed propolis samples by L. plantarum ISL-2 and ATCC 8014 strain with low allergen molecule content has also the same effect in potassium bromate toxicity in CCD841 colon cell. Our data contributed that propolis as a natural compound might be a good candidate due to its minimal toxicity and lack of any adverse effects to prevent carcinogenic effect of potassium bromate.

LC-MS/MS measurement of leukocyte cystine; effect of preanalytic factors.

Cystinosis is an autosomal recessive disorder characterized by the accumulation of cystine in lysosomes, causing irreversible damage to organs, especially the kidneys. Intracellular leukocyte cystine concentrations are used to diagnose cystinosis and to monitor cysteamine treatment. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method without derivatization capable of measuring leukocyte intracellular cystine concentrations. During development, the effects of using three different protein precipitation agents were evaluated in terms of sensitivity and the matrix effect, with 12% trichloroacetic acid providing the highest sensitivity. The effects of different blood collection tubes were also assessed in terms of recovery, matrix effect, and protein content. Compared to other methods, our method was quicker (run time of 3 min), was linear over the range 0.078-100 µM, and had lower limits of detection (0.0192 µM) and quantification (0.0582 µM). The intra-day and inter-day reproducibility %CVs were ≤10%. and the method had excellent recovery rates (94%-106%). Other parameters including matrix selectivity, injection carryover, leukocyte lysate stability were also validated and met the acceptance criterias of European Medicines Agency (EMA) Guideline. The assay was successfully applied to quantify cystine leukocyte concentration in healthy and cystinosis patients.

Methods for Determination of α-Glycosidase, ß-Glycosidase, and α-Galactosidase Activities in Dried Blood Spot Samples.

The lysosomal storage diseases (LDSs) are a heterogeneous group of inherited genetic disorders caused by defects of lysosomal proteins. The accumulation of undigested substrates from different catabolic pathways leads to cellular dysfunction. LSDs generally presents during early childhood and have a devastating impact on the families and on public health. Over the years, approaches for treatment of some LSDs have been developed with different strategies. Increasing availability of treatments of these diseases has accelerated the development of new methods and techniques for rapid diagnosis in patients with clinical indication.The use of dried blood spot (DBS) test has been proposed as a first tier test to identify patients with Gaucher, Pompe, and Fabry diseases. DBS usage is advantageous for the purpose of screening as it is non-invasive, sensitive, has low-cost and fast turnaround time compared to measurements in leucocyte and/or fibroblast culture. This chapter focuses on the activity measurement of three lysosomal enzymes (α-glucosidase, ß-glucosidase, and α galactosidase) in DBS samples by using fluorescent substrates and by the LC-MS/MS (liquid chromatography-mass spectrometry) method. All steps of the methods, from preparation of the solutions to calculation of the enzyme activity, will be explained in detail.

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey.

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.

Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children.

A correlation has been clearly shown between inflammation markers and subclinical atherosclerosis markers in the early stages of atherogenesis in subjects with familial hypercholesterolemia (FH). The aim of this study was to investigate potential inflammation markers in the diagnosis of atherosclerosis in children with FH. A total of 48 dyslipidemic children and 24 healthy age-matched control subjects were taken into study. Inflammation and macrophage activation markers (hsCRP, myeloperoxidase, chitotriosidase, YKL-40, TNF-α, IL-6, IL-18, MMP-1 and MMP-9) and lipid parameters of all patients were measured. Carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD) levels were determined. Our data suggested that clinically evidenced (by cIMT and FMD levels) atherosclerosis starts in the early ages in hypercholesterolemic children. Higher cholesterol levels strongly correlated with macrophage activation markers (ChT, YKL-40 and myeloperoxidase). ChT and YKL-40 seem to be the more predictable markers of atherosclerosis even in early ages (<6 years old) than other classical inflammation markers such as hs-CRP, IL-6 and TNF-α.

Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic plaque formation.

BACKGROUND: The aim of this study was to determine the oxidant-antioxidant status and lipid peroxidation products, as well as paraoxonase and atherosclerotic plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to investigate the effects of atorvastatin in the atherosclerotic process. METHODS: Forty male New Zealand rabbits were divided into four groups, ie, a control group receiving standard pellets, a group receiving atorvastatin therapy, a hypercholesterolemic group receiving an atherogenic diet, and a group receiving both an atherogenic diet and atorvastatin. RESULTS: The atherogenic diet increased the levels of low-density lipoprotein (LDL) thiobarbituric acid reactive substances (1.84 vs 3.79 nmol/mg protein) and LDL-conjugated diene (147 vs 318 µmol/mg protein) after induction of oxidation by Cu(2+), despite an increase of superoxide dismutase activity. Treatment with atorvastatin limited LDL oxidation significantly (LDL thiobarbituric acid reactive substances 2.19 nmol/mg protein, LDL-conjugated diene 222 µmol/mg protein). Paraoxonase, which prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids, showed a pronounced decrease in the group receiving the atherogenic diet (110 U/L to 28 U/L), and atorvastatin treatment increased paraoxonase activity. Histological examination of arcus aorta tissues from the hypercholesterolemic group showed abundant plaque formation surrounding and obstructing the lumen, whereas treatment with atorvastatin prevented or limited plaque formation, keeping the plaque thin and localized. CONCLUSION: Atorvastatin has dramatic antiatherosclerotic effects, part of which seems to be due to the antioxidant features of the parent drug and/or its metabolites, favoring inhibition of LDL oxidation.

Lipids as key players in Alzheimer disease: alterations in metabolism and genetics.

Advances in Alzheimer Disease (AD) research suggest that central nervous system (CNS) lipids play a key role in the pathogenesis. This role is attributed to the rich lipid content of CNS structures and the presence of blood brain barrier which disables the exchange of lipids between CNS and plasma. Among these lipids, cholesterol is a unique molecule provided mainly by its de novo synthesis in the CNS. Special apolipoproteins used for its efficient recycling within the CNS and special oxysterols formed that are specific to brain all contribute to the unique properties of the molecule. Above all, the presence of cholesterol in the membrane enables it to function as a regulator of a number of protein related processes such as the beta-amyloid precursor protein cleavage. Cholesterol reducing agents such as statins are recently proposed to have a protective role in AD. This review will focus on the role of cholesterol metabolism and genetics in AD. Current literature investigating the relationship between cholesterol and AD will be evaluated from the pathophysiological perspective. Genetic studies concerning proteins which are involved in the CNS cholesterol metabolism will also be summarized in the hope that genomics may stimulate further studies and thus contribute to a more clear understanding of the molecular mechanisms in the pathophysiology of AD.

Preventive effect of nebivolol on contrast-induced nephropathy in rats.

BACKGROUND: Altered renal vasodilatation and oxidative stress are important mechanisms of contrast-induced nephropathy (CIN). The aim of the present study was to assess the effect of nebivolol, a beta blocker, on prevention of CIN. We hypothesized that nebivolol may prevent CIN due to its renal vasodilatation and antioxidant effects. METHODS: Thirty-two Wistar-albino rats were divided into four groups (n = 8 each): control (C), contrast media (CM), nebivolol (N), and nebivolol + contrast media (NCM). CIN was induced by administration of intravenous high-osmolar contrast media diatrizoate (6 ml/kg) after 72 h of dehydration. Nebivolol (2 mg/kg) was given internally once daily for 5 days. Kidney function parameters, nitric oxide metabolites and oxidative stress markers were measured. Kidneys were excised for pathological evaluation. RESULTS: The decrease of creatinine clearance was 0.180 +/- 0.11 mg/dl in CM, and 0.030 +/- 0.10 mg/dl in NCM (P = 0.01). Microproteinuria was ameliorated using nebivolol (P = 0.001). Serum protein carbonyl content, malonyldialdehyde and kidney thiobarbituric acid-reacting substances levels were higher in CM than in C (P = 0.003, P < 0.001 and P = 0.034, respectively) and serum thiol was lower in CM than in C (P = 0.001). However, oxidative stress markers were similar in NCM and C. Diatrizoate decreased kidney nitrite levels, but nebivolol increased them (P = 0.027). Nebivolol attenuated the tubular necrosis, proteinaceous casts and medullary congestion, although significant protective effects, were observed in tubular necrosis (P = 0.001) and proteinaceous cast (P < 0.001). CONCLUSION: This study demonstrated the protective role of nebivolol against CIN.

Pomegranate wine has greater protection capacity than red wine on low-density lipoprotein oxidation.

Although there is a large body of evidence on the main role of red wine in protection of low-density lipoprotein (LDL) against oxidation, there are few data on the role of pomegranate juice, which has high phenolic content. We conducted this study considering the possible importance of pomegranate wine as an antioxidant and in order to make a comparison between red and pomegranate wines. The phenol levels of pomegranate and red wines (4,850 mg/L gallic acid equivalents and 815 mg/L gallic acid equivalents, respectively) were in accordance with their total antioxidant activity (39.5% and 33.7%, respectively). Both wines decreased LDL-diene levels following a 30-minute incubation period compared with controls (145 +/- 3.2 micromol/mg of LDL protein). However, pure pomegranate wine demonstrated a greater antioxidant effect (P < .01) on diene level (110 +/- 4.6 micromol/mg of LDL protein) than pure red wine (124 +/- 3.2 micromol/mg of LDL protein). In conclusion, we suggest that pomegranate wine has potential protective effects toward LDL oxidation, and it may be a dietary choice for people who prefer fruit wines.

Serum paraoxonase 1 activity and oxidative markers of LDL in patients with cardiac syndrome X.

OBJECTIVE: Myocardial ischaemia in cardiac syndrome X (CSX) is believed to be due to microvascular dysfunction. Increased oxidative stress is one of the suspected mechanisms of microvascular dysfunction. The aim of this study was to evaluate the oxidative status in patients with CSX, by determining serum paraoxonase-1 (PON 1) activity in addition to LDL-oxidation markers. METHODS AND RESULTS: This cross-sectional study consisted of patients with CSX (group I, n = 30), patients with coronary artery disease (group II, n = 31), and healthy controls (group III, n = 32). Lipid parameters, PON-1 activity, and LDL oxidation markers (conjugated-diene and thiobarbituric acid-reactive substance-TBARS) were measured. Endothelium-dependent vasodilatation was determined by brachial artery ultrasonography. There were no significant differences in serum LDL, apolipoprotein-B, baseline LDL-diene, and LDL-TBARS levels between groups. There were no differences in both apolipoprotein-A1 and HDL levels between group I and group III. Apolipoprotein-A1 and HDL levels were significantly lower in group II than group I patients (P < 0.001). PON-1 activity was lowest in group II patients. Average PON-1 activity in group I was in between of group II and group Ill. The percent change of LDL-diene levels after stimulation was significantly higher in group II than in groups I and III (P = 0.005 and P = 0.02, respectively). The percent change of LDL-TBARS levels was lowest in group I (P = 0.03). There was a moderate correlation between endothelium-dependent vasodilatation and PON-1 activity in group I (r = 0.43, P = 0.04). CONCLUSIONS: Enhanced oxidative stress might be one of the causes of impaired endothelial functions resulting in myocardial ischaemia and chest pain in patients with CSX. The relatively preserved HDL and apolipoprotein-A1 levels in patients with CSX might be a protective mechanism against progression of coronary microvascular dysfunction to atherosclerotic coronary artery disease.

Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia.

Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor beta1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group (P<0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU.

Markers of long-term exposure to organophosphorus pesticides in farmers who work in viniculture and tobacco production in Turkey.

ABSTRACT The first aim of this study was to evaluate the degree of organophosphorus (OP) pesticides' exposure in viniculture and tobacco production workers via physical examination (neurology and general health aspect) and analysis of paraoxonase (PON1) and butyrylcholinesterase (BuChE) activities. The second aim was to investigate if PON1 polymorphism plays any role in long-term OP exposure. A total of 93 farmers who work as applicators in agriculture were studied. The data were evaluated according to agricultural type, and although the total exposure time was similar in both areas, BuChE and PON1 activities of farmers who work in tobacco production were lower. Overall, BuChE and PON1 activities showed a depletion in the farmer group compared to age-matched controls. When the farmers were categorized according to the number of their symptoms, the BuChE activities of farmers who had two or more symptoms were found to be depleted (n = 43, 2948 +/- 756) compared to farmers who had one or no symptoms (n = 37, 3356 +/- 659). Allele frequencies of patients and controls for positions 55 and 192 were similar to Turkish population data and there was no association between the allele polymorphism and symptoms/signs of long-term exposure. Our results indicate that there is an important inhibition of PON1 activity in chronic OP poisoning, and this together with BuChE activity might well be used as a reliable index of chronic exposure to OP.

The effect of melatonin on lipid peroxidation and nitrite/nitrate levels, and on superoxide dismutase and catalase activities in kainic acid-induced injury.

Kainic acid (KA) initiates neuronal injury and death by inducing oxidative stress and nitric oxide release from various regions of the brain. It was recently shown that melatonin has free radical-scavenging action and may protect against kainate-induced toxicity. In order to assess the possible supportive effect of melatonin treatment in KA-induced injury in the rat brain cortex, we determined malondialdehyde (MDA) levels as an index of lipid peroxidation, and assessed the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of nitrite/nitrate 35 male rats were divided into five groups, each receiving a different intraperitoneal treatment: saline solution (0.2 ml), kainic acid (15 mg/kg), melatonin (20 mg/kg), KA then melatonin (each as above, 15 min apart), or melatonin then KA (each as above, 30 min apart). Administration of KA caused an about five-fold increase in the catalase activity and an increase in the SOD activity in the cortex relative to the activities for the controls. Treatment with melatonin 15 min after KA injection kept malondialdehyde levels and catalase and superoxide dismutase activities at the normal levels, and led to an increase in the levels of nitrite/nitrate. Our data suggests that melatonin treatment following KA administration has a protective effect on antioxidant enzyme activities and thus supports the role of melatonin and oxidative stress in the regulation of antioxidative enzyme activity.

Insulin-like growth factor attenuates apoptosis and mucosal damage in hypoxia/reoxygenation-induced intestinal injury.

OBJECTIVE: Necrotizing enterocolitis (NEC) is a potentially lethal disease among premature infants. The aim of the present study was to investigate whether hypoxia-reoxygenation (H/R)-induced intestinal injury was due to increased apoptosis of the intestinal mucosa in young mice and whether pre-treatment of the animals with recombinant human insulin-like growth factor-I (IGF-I), a known anti-apoptotic factor, could protect the intestinal cells from H/R-induced apoptosis or intestinal injury. STUDY DESIGN: Young mice were divided into three groups: group 1 mice (H/R) were hypoxia-reoxygenation; group 2 mice (H/R + IGF-I) were treated with recombinant human IGF-I by intraperitoneal injection (1 mug/g b.w. once daily) for 7 days, and group 3 mice served as control. Hypoxia was induced by placing young mice in a Plexiglas chamber consisting of 10% oxygen for 60 min. After hypoxia, the young mice were reoxygenated for 10 min with 100% oxygen. Intestinal generation of substances reactive to thiobarbituric acid (TBARS) and active caspase-3 were measured in H/R-induced intestinal injury. RESULTS: Increased numbers of apoptotic cells (apoptotic index) across the villi in young mice subjected to H/R were observed with the TUNEL reaction whereas few apoptotic cells existed in the control animals. In addition, H/R-induced intestinal damage in the H/R + IGF-I group was greatly attenuated, with necrosis limited partially to the mucosa. Tissue-active caspase-3 levels in the H/R group were found to be significantly higher when compared with that of the H/R + IGF-I group of mice and control. However, TBARS concentrations in the intestine were similar in H/R groups when compared to the intestine of control animals. CONCLUSION: The present study suggests that both necrosis and apoptosis, via mechanisms occurring due to oxygen-derived free radicals and activation of caspase-3, play a role in the pathogenesis of H/R-induced bowel injury. We also show that IGF-I protect intestinal mucosa from necrosis and apoptosis from intestinal H/R injury.