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Introduction: Depression in Alzheimer's disease (AD) differs from major depression in terms of clinical features and treatment. Antidepressants do not provide the expected benefits in depressive symptoms accompanying cognitive decline in AD, suggesting distinct mechanisms. Emerging research suggest that compromised mitophagy, the selective removal of damaged mitochondria, may contribute to the pathogenesis of AD. However boosting nicotinamide adenine dinucleotide (NAD+) to induce mitophagy reduces amyloid β (Aβ) aggregation and enhances cognitive function in AD models (Kerr et al.,Trends Neurosci 2017;40:151-66). Nevertheless, data on NAD's impact on depression in AD remains limited. Objectives: This study aimed to examine the impact of the NAD+ precursor nicotinamide riboside (NR) on cognitive and neuropsychiatric symptoms in a AD rat model. Methods: To induce the AD, a single dose of 5 μl Aβ1-42 was injected into each lateral ventricle of rats (day 0), while the control group received an intracerebroventricular (icv) saline (0.9%NaCl).Four experimental groups were designed: control (icv saline+po saline), NR (icv saline+po NR), Aβ (icv Aβ+po saline), and Aβ+NR (icv Aβ+po NR).After the injection, to reduce Aβ clearance (Kang et al. Science. 2009;32 1005-7.) rats were subjected to 96 hours of sleep deprivation.Starting from day 6, rats were given either 700 mg/kg oral NR or saline, and handling test scores were recorded daily.The procedures were repeated daily until the rats were sacrificed on day 28.Behavioral experiments were randomly conducted at the end, and statistical analysis was performed using repeated measures ANOVA, followed by the Tukey post hoc test. Results: Passive avoidance test results showed that the Aβ group had the shortest latency to enter the dark area. However, the Aβ+NR group exhibited a prolonged latency compared to the Aβ group (F(3,2)=5.5;p<0.05). Aβ injection induced depressive-like behavior in rats, as indicated by the forced swim test (FST) for behavioral despair and the sucrose preference test (SPT) for anhedonia. In AD rats treated with NR (Aβ+NR), Aβ-induced depressive-like behavior was reduced, with lower FST immobility scores (F(3,2)=6.2;p<0.05) and increased sucrose preference in the SPT (F(3,2)=7.5;p<0.05). There were no significant differences in anxiety-like behaviors among the groups, assessed by the time spent in the open arm in the elevated plus maze test (F(3,2)=1.9;p>0.05). During the 28-day monitoring period, the Aβ+NR group of rats exhibited a more rapid decrease in aggression levels compared to the other groups in the handling test. This decrease was significant between days 7 and 10 compared to the Aβ group (F(48,5)=1.5;p<0.05). Conclusions: NR improved memory, reduced depressive behavior, and lowered aggression in AD rats. This suggests that NAD+ precursor NR effectively treats cognitive decline and neuropsychiatric symptoms in an AD model. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis Optica Spectrum Disorders (NMOSD) and Multiple Sclerosis (MS) are primary demyelinating diseases of the central nervous system (CNS) with similar clinical features, complicating early differential diagnosis and treatment decisions. While both humoral and cellular immunity contribute to their immunopathogenesis, the complement system's role remains unclear. We considered complement-dependent cytotoxicity might have different roles in the pathophysiology of these diseases. Predictive value of C3 and C4 complement levels at the first attack for the definitive diagnosis aimed to be investigated., Methods: Treatment-naive, 14 seronegative (SN) NMO, 28 aquaporin-4-positive [AQP4(+)] NMO, 23 myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and 15 MS adult patients were included. Serum C3 and C4 levels were evaluated retrospectively. Complement levels were statistically adjusted according to the age of the patients and C3/C4 ratio was used to increase statistical power., Results: We found that C4 levels were lower and C3/C4 ratio was higher in SNNMO and AQP4(+)-NMO groups compared to the MS group. It has been determined that 5.32 and 4.85 cut-off values of the C3/C4 ratio can discriminate SNNMO and AQP4(+)-NMO groups from MS., Conclusion: The classical complement pathway in SNNMO and AQP4(+)-NMO was thought to be more affected compared to MS, as activation of the classical pathway predominantly decreases the level of C4. Since the involvement of the complement system pathways at different levels may be presented with the C3/C4 ratio, it seems likely that this ratio may have value as a candidate biomarker in the differential diagnosis of primary CNS demyelinating diseases., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2025. Published by Elsevier B.V.)

Background: GABA, a key inhibitory neurotransmitter, has synaptic and extrasynaptic receptors on the postsynaptic neuron. Background GABA, which spills over from the synaptic cleft, acts on extrasynaptic delta subunit containing GABAA receptors. The role of extrasynaptic GABAergic input in migraine is unknown. We investigated the susceptibility to valid migraine-provoking substances with clinically relevant behavioral readouts in Genetic Absence Epilepsy of Rats Strasbourg (GAERS), in which the GABAergic tonus was altered. Subsequently, we screened relevant GABAergic mechanisms in Wistar rats by pharmacological means to identify the mechanisms., Methods: Wistar and GAERS rats were administered nitroglycerin (10 mg/kg) or levcromakalim (1 mg/kg). Mechanical allodynia and photophobia were assessed using von Frey monofilaments and a dark-light box. Effects of GAT-1 blocker tiagabine (5 mg/kg), GABAB receptor agonist baclofen (2 mg/kg), synaptic GABAA receptor agonist diazepam (1 mg/kg), extrasynaptic GABAA receptor agonists gaboxadol (4 mg/kg), and muscimol (0.75 mg/kg), T-type calcium channel blocker ethosuximide (100 mg/kg) or synaptic GABAA receptor antagonist flumazenil (15 mg/kg) on levcromakalim-induced migraine phenotype were screened., Results: Unlike Wistar rats, GAERS exhibited no reduction in mechanical pain thresholds or light aversion following nitroglycerin or levcromakalim injection. Ethosuximide did not reverse the resistant phenotype in GAERS, excluding the role of T-type calcium channel dysfunction in this phenomenon. Tiagabine prevented levcromakalim-induced mechanical allodynia in Wistar rats, suggesting a key role in enhanced GABA spillover. Baclofen did not alleviate mechanical allodynia. Diazepam failed to mitigate levcromakalim-induced migraine phenotype. Additionally, the resistant phenotype in GAERS was not affected by flumazenil. Extrasynaptic GABAA receptor agonists gaboxadol and muscimol inhibited periorbital allodynia in Wistar rats., Conclusion: Our study introduced a rat strain resistant to migraine-provoking agents and signified a critical involvement of extrasynaptic δGABAergic receptors. Extrasynaptic δ GABAA receptors, by mediating constant background inhibition on the excitability of neurons, stand as a novel drug target with a therapeutic potential in migraine., (© 2024. The Author(s).)

Background: Various microorganisms which increase the mortality rate in the intensive care unit (ICU) cause microbial colonization of the nasogastric tube (NGT) and use the NGT as a reservoir., Aim: To detect the colonization on the NGT and to determine the effect that training regarding hand hygiene, NGT management, and enteral feeding (EF) provided to ICU nurses and auxiliary service staff (ASS) has on the level of NGT colonization., Study Design: A quasi-experimental pre-test and post-test control design was used in this study. Microbial samples were taken from the outer and inner parts of NGT. The microorganisms were categorized as: group 1, no risk; group 2, low risk pathogenic; group 3, high-risk pathogenic group. The training was given to nurses (n = 15) and ASS (n = 7). Hand hygiene, NGT, and EF care training are provided to nurses and ASS by researchers. A total of three training sessions were scheduled to be held in 3 weeks so that all health care staff members were trained. Each session lasted 2 h in total. Patients were assigned to a group if one of the microorganisms presented on the outer surface of the patient's feeding tube and/or on the hub. The hand hygiene compliance was evaluated by direct observation according to the World Health Organization hand hygiene indications., Results: The study was conducted with 46 patients. Evaluating the patients for the presence of microorganisms before education revealed that 4.3% were in group 1, 21.8% were in group 2, and 73.9% were in group 3. After the education, evaluating the samples for the presence of microorganisms revealed that 39.1% were in group 1, 13% were in group 2, and 47.8% were in group 3. A statistically significant difference was found between the number of samples included in the groups after the participants had received training (H = 8.186; p = .017)., Conclusions: An NGT could act as a reservoir of microbial colonization and high-risk microorganisms could be on the tube. Providing training not only to nurses but also to ASS will help reduce the risk of colonization., Relevance to Clinical Practice: Eliminating such colonization with effective hand hygiene during NGT feeding is a cost-effective method. Providing training not only to nurses but also to ASS will help obtain the optimum benefit from patient care., (© 2022 British Association of Critical Care Nurses.)

Background: Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura., Methods: Wistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark-light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood-brain barrier integrity in cortex was examined with Evans blue assay., Results: LVC and NTG administration robustly reduced periorbital mechanical thresholds in rats and induced anxiety-like behaviors and photophobia within 30 and 120 min, respectively. LVC induced migraine-like phenotype recovered in 2 h while NTG group did not fully recover before 4 h. Both LVC and NTG did not provoke DC (direct current) shift, EEG alterations or cortical c-fos expression characteristic to CSD. LVC did not induce de novo CSD and affect KCl (potassium chloride)-induced CSD parameters except for an increase in propagation failure. However, NTG significantly increased both CSD susceptibility and propagation failure. Somatosensory evoked potential (SSEP) configurations were not altered in both LVC and NTG groups, but SSEP latencies were prolonged after CSD. Acute LVC or NTG injection did not increase cortical BBB permeability., Conclusions: Single LVC administration induced the fastest manifestation and recovery of acute migraine-like phenotype which was not mediated by CSD waves in the cerebral cortex. We suppose LVC triggered rapid-onset migraine-like symptoms are probably related to functional alterations in the trigeminal nociceptive system and K +  channel opening properties of LVC. Understanding the neurobiological mechanisms of this nociceptive window, may provide a novel target in migraine treatment., (© 2023. The Author(s).)

Alzheimer's Disease (AD) is the leading cause of dementia and, at the time of diagnosis, half of AD patients display at least one neuropsychiatric symptom (NPS). However, there is no effective therapy for NPSs; furthermore, current treatments of NPSs accelerate cognitive decline. Due to the ineffectiveness and negative consequences of current treatments for NPSs, new approaches are strongly needed. Currently, indications for vagal nerve stimulation (VNS) include epilepsy, stroke rehabilitation and major depression but not NPSs or AD. Therefore, we investigated whether chronic VNS can treat NPSs in a rat model of AD. Here, we report the intracerebroventricular injection of amyloid-β (Aβ) results in depression-like behaviors and memory impairment in rats. Chronic VNS (0.8 mA, 500 μs, 30 Hz, 5 min/day) showed strong antidepressant and anxiolytic effects, and improved memory performance. Additionally, the anxiolytic effect of VNS was retained in the non-Aβ-treated rats. VNS also decreased aggressiveness and increased locomotor activity in both Aβ-treated and non-Aβ-treated rats. Recent studies showed VNS alters glutamatergic receptor levels, thus levels of GluA1, GluN2A, and GluN2B were determined. A significant reduction in GluN2B levels was seen in the hippocampus of VNS-treated groups which may relate to the anxiolytic effects and increased locomotor activity of VNS. In conclusion, VNS could be an effective treatment of NPSs, especially depression and anxiety, in AD patients without impairing cognition., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Turkey is one of the major exporters of mandarins in the Mediterranean region. Seedlessness in citrus, which is one of the most desired fruit quality traits, especially in fresh mandarin export markets, can be obtained via triploidy as in many fruit species. Triploid plants can be recovered by 2x × 2x hybridizations in citrus, as well as 2x × 4x and 4x × 2x crosses. Hence, we aimed to develop local triploid hybrids by using the embryo rescue technique in five crosses using eight different citrus varieties in the present study., Methods and Results: Embryos isolated from abortive seeds derived by 135 days after pollinations were cultured on modified Murashige and Tucker (MT) medium by adding different levels of GA 3 to achieve a high germination rate. A population of 574 plants was developed as a result of embryo rescue. After screening the ploidy levels of this 574-plant population with the aid of flow cytometry, 4 triploids from 'Encore' × 'Murcott', 8 triploids from 'Fortune' × 'Willow leaf', 1 triploid from 'Kiyomi' × 'Murcott', and 1 triploid from 'Ortanique' × 'Murcott' hybridization were recovered. Triploid hybrid plants and related parents were analyzed with SSR markers heterozygotic for parental mandarin varieties. In addition, we evaluated stomatal characteristics of diploid and triploid hybrids obtained from different crosses. Stomatal traits of diploid and triploid hybrids in all crosses significantly differed except the stomata index., Conclusions: Genotyping of triploid plants confirmed using Simple Sequence Repeat (SSR) molecular markers and five SSRs were able to identify three alleles of triploid hybrids. Selected triploid mandarin hybrids have been grafted on several rootstocks for field trials and are in the process of yield and quality performances., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Herein, we report the synthesis of taurine incorporated (sulfur containing organic molecule derived from methionine and cysteine) hybrid nanoflowers (thNFs) with an intrinsic peroxidase-mimic and antimicrobial activities in the presence of H 2 O 2 . Formation of thNFs using non-enzyme molecules was for the first time and systematically studied as a function of the taurine concentration, types of metal ions (Cu 2+ , Fe 2+ and Fe 3+ ) and pH values of reaction solution. The peroxidase like activities of thNFs rely on Fenton-like reaction against guaiacol used as a model substrate. The efficiency of Fenton reaction can be attributed to porous structure and presence of ions of transition elements in the thNFs. The thNFs were further characterized using FTIR, XRD, SEM and EDX. The thNFs also showed remarkable antimicrobial properties against S. aureus, E. coli, B. cereus and C. albicans. We claim that nonprotein-based NFs can be considered as new generation nano-biocatalysts as an alternative to enzymes and can be used in various medicinal, biochemical, immunological, biotechnological, and industrial applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Ischemia-reperfusion (I-R) injury is a serious problem caused by vascular trauma, tourniquet use and/or compartment syndrome. Studies have reported that skeletal muscle function is impaired due to the lower extremity I-R injury. There are insufficient studies on the treatment methods used for the recovery of dysfunction. This study is designed to investigate the effects of trans-cinnamaldehyde (TCA), a volatile oil of cinnamon structure, on the contractile dysfunction due to I-R injury of rat extensor-digitorum-longus (EDL) muscle., Materials and Methods: Sprague-Dawley rats were randomly divided into three groups. Except for the animals in the control group, all animals received saline (3-ml/kg) or TCA solution (30-mg/kg) which was administered orally three times with an 8-h interval before ischemia. After 24-hours, experimental groups were subjected to 3-h of lower extremity ischemia followed by 5-h reperfusion period. Then, the compound muscle action potential (CMAP) and mechanical activity of muscle were recorded using the standard electro-biophysical techniques., Results: There was a decrease in the maximum contractile force in I-R group compared to the control group ( p  < 0.05). Oxidative damage indicator (MDA) and antioxidant indicator (CAT) increased in the EDL muscle and serum samples in the I-R group ( p  < 0.05). Laminin expression showed a reduction in the I-R group ( p  < 0.05). It was seen that TCA achieve again the maximum contraction force in the EDL muscle ( p  < 0.05) and maintain the expression of laminin ( p  > 0.05)., Conclusion: We concluded that TCA has a potential protective effect with antioxidant effects against I-R injury and may maintain laminin levels.

The aim of the present study was to systematically investigate the effects of chronic exposure to extremely low-frequency electromagnetic field (ELF-EMF) on electrophysiological, histological and biochemical properties of the diaphragm muscle in rats. Twenty-nine newly weaned (24 days old, 23-80 g) female ( n = 15) and male ( n = 14) Wistar Albino rats were used in this study. The animals were randomly divided into two groups: the control group and the electromagnetic field (EMF) group. The control group was also randomly divided into two groups: the control female group and the control male group. The EMF exposure group was also randomly divided into two groups: the ELF-EMF female group and the ELF-EMF male group. The rats in the ELF-EMF groups were exposed for 4 h daily for up to 7 months to 50 Hz frequency, 1.5 mT magnetic flux density. Under these experimental conditions, electrophysiological parameters (muscle bioelectrical activity parameters: intracellular action potential and resting membrane potential and muscle mechanical activity parameter: force-frequency relationship), biochemical parameters (Na + , K + , Cl - and Ca +2 levels in the blood serum of rats; Na + -K + ATP ase enzyme-specific activities in muscle tissue; and free radical metabolism in both muscle tissue and serum) and transmission electron microscopic morphometric parameters of the diaphragm muscle were determined. We found that chronic exposure to ELF-EMF had no significant effect on the histological structure and mechanical activity of the muscle and on the majority of muscle bioelectrical activity parameters, with the exception of some parameters of muscle bioelectrical activity. However, the changes in some bioelectrical activity parameters were relatively small and unlikely to be clinically relevant.

We report synthesis of monodispersed, stable, and colloidal gold nanoparticles (Au NPs) using anthocyanin-riched red raspberry ( Rubus idaeus ), strawberry ( Fragaria ananassa ), and blackberry ( Rubus fruticosus ) extracts as functions of concentration of HAuCl 4 ·3H 2 O and berries extract, reaction time, and reaction pH values (pHs) and demonstrate their unique stability in highly concentrated salt (sodium chloride, NaCl) solutions. The catecholamine group of anthocyanin molecules give preferential coordination reaction with gold ions (Au 3+ ) for creating anthocyanin-Au 3+ complexes, which may lead to initiation of nucleation for seed formation, and then, oxidation of catecholamine results in a flow of electrons from anthocyanins to Au seeds for anisotropic growth. Finally, the surface of the Au NPs is saturated with anthocyanins, and formation of monodispersed and stable Au NPs with narrow size distribution is completed. We also report the effects of some experimental parameters including concentrations of Au 3+ ions and barrier extracts, reaction time, and pHs on formation of the Au NPs with rational explanations. The long-term colloidal stability of the Au NPs in the 400 mM NaCl solution was comparatively studied with commercial Au NPs (citrate capped). As results show that anthocyanin-riched berry extracts directed Au NPs we proposed here can be considered as promising and safe tools for biomedical applications owing to their highly much colloidal dispersibility and salt tolerance properties., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

The discovery of functional organic-inorganic hybrid nanoflowers (FNFs) consisting of proteins/enzymes as the organic components and Cu(ii) ion as the inorganic component has made an enormous impact on enzyme immobilization studies. The FNFs synthesized by an encouraging and novel approach not only showed high stabilities but also much enhanced catalytic activities as compared to free and conventionally immobilized enzymes. A recent development demonstrated that FNF formation has moved beyond the initial discovery in which enzymes and Cu 2+ ions used as the organic and inorganic parts, respectively, are replaced with new organic (chitosan, amino acid and plant extracts) and inorganic (Cu 2+ and Fe 2+ ) materials. The new organic materials incorporated into FNFs act as Fenton-like agents and then show peroxidase-like activity owing to the metal ions and the porous structure of FNFs in the presence of hydrogen peroxide (H 2 O 2 ). All FNFs have been widely utilized in many different scientific and industrial fields due to their greatly enhanced activities and stabilities. This review focuses primarily on the preparation, characterization, and bioanalytical applications of FNFs and explains the mechanisms of their formation and enhanced activities and stabilities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Regular physical exercises may help people to be more resistant to everyday problems; however, how acute and intense exercises affect the heart tissues functioning with maximum capacity and how melatonin changes the effect of acute and intense exercises are still not obvious. We aimed to comprehend whether melatonin intravenous injection supports the oxidative/antioxidative conditions and energy charge in heart tissues of rats exposed to acute swimming exercise., Methods: Thirty Wistar-albino male rats were categorized into 3 groups with equal number of subjects. Control group performed no application, and acute intensive swimming exercise group were subjected to acute intensive swimming exercise for 30 minutes, and melatonin group were applied 25 mg/kg single dose melatonin administration prior to 30 minutes acute intensive swimming exercise. The levels of malondialdehyde (MDA), and superoxide dismutase, catalase and glutathione peroxidase activities were measured by spectrophotometric method; and the levels of 3-nitrotyrosine (3-NT) and energy charge were determined by a high performance liquid chromatography., Results: Tissue MDA and 3-NT levels of the acute intensive exercise group were found to be higher than the control group. It was also found that the melatonin administration increased the energy charge and antioxidant activities, while decreased tissue MDA and 3-NT levels in heart tissues. Our results provide evidence for melatonin that can exert potent protective effects on oxidative stress and energy charge for heart tissues in acute swimming exercise., Conclusions: These findings suggest that the direct beneficial effects of melatonin could be potentially applied on prevention of oxidative stress and energy deficit.

This study was conducted to determine the effects of hempseed (H) on performance, carcass traits, and antioxidant activity in Japanese quail (Coturnix coturnix japonica). A total of 192 quail with seven-days old were divided into four experimental groups with four replicates. The treatments were; i) Control diet (C, no hempseed); ii) 5% hempseed in diet (H5); iii) 10% hempseed in diet (H10); and iv) 20% hempseed in diet (H20). The body weight (BW) and feed intake (FI) of quail was determined at 7, 21 and 42 d of age. At 42 d of age four quail were slaughtered and the carcass and internal organ traits were determined. Malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), nitric oxide (NO) and total protein were determined in the blood serum end of the experiment. The BW of the groups were not significant at 7 and 21 d, however in the 20% hempseed group BW decreased at 42 d (p<0.05). The FI and feed conversion ratio were not significant among the treatment groups. The carcass, liver, intestine and heart weight and their percentage to carcass were significantly differ in treatment groups (p<0.05). The serum MDA and NO decreased in hempseed addition (p <0.001). The serum SOD, CAT and GSH-Px were increased by hempseed supplementation (p<0.001). In conclusion, hempseed supplementation to quail diets may not improve quail performance traits but increase antioxidant activity in blood.

Purpose: In this study, we compare the concentrations of the essential trace elements chromium (Cr), copper (Cu), selenium (Se), manganese (Mn), boron (B) and zinc (Zn) in both pterygium and normal conjunctiva and investigate the role they play in the development of pterygium., Methods: Included in the study were 38 patients with pterygium and 38 control patients in matching age groups who had been operated on for strabismus or cataracts and in whom conjunctiva samples were collected from the nasal limbus area. All conjunctiva samples were kept at -80 °C until the performance of the biochemical investigations. The B, Cr, Mn, Cu, Zn and Se levels in the samples were then measured. The levels of all tissue trace elements were determined by using Agilent 7500a Inductively Coupled Plasma-Mass Spectrometer (Agilent Technologies, Santa Clara, CA)., Results: Cr, Mn, Zn and Se levels are significantly lower in the study group as compared to those of the control group (p < 0.001 for all four values). Regarding the level of B, there was no significant difference between the groups. The Cu levels of almost all subjects in the control group and all subjects in the pterygium group were under the detection limit., Conclusions: These findings indicate that remarkable differences in Mn, Zn, Se and Cr levels exist in pterygium tissues. Further investigation of electrolyte composition of the conjunctiva is needed to understand the genesis and developmental mechanism of pterygium.

We aimed to measure oxidative stress parameters and paraoxonase-1 (PON-1) enzyme activities in chronic hemodialysis (HD) patients and to investigate whether HD membrane permeability has any influence on those measures. Forty-seven HD patients and 24 controls were enrolled. At the first step of the study, all HD patients had undergone HD treatment via "low-flux" membranes for 4 weeks. At the second step of the study, the membranes were switched to "high-flux" membranes and HD treatments were also performed via "high-flux" membranes for 4 weeks. Blood samples were withdrawn after completion of 4 weeks treatment for each membrane. Total oxidant status (TOS), total antioxidant status (TAS), and paraoxonase and arylesterase activities were measured in blood samples of the patients and the controls. TOS and oxidative stress index (OSI) of both membranes were higher than controls (all, P < 0.05), while TAS and paraoxonase and arylesterase activities were lower (all P < 0.05). Paraoxonase (P < 0.05, r = -0.437 and P < 0.05, r = -0.453, respectively) and arylesterase (P < 0.05, r = -0.333 and P < 0.05, r = -0.371, respectively) activities of "low-flux" and "high-flux" membranes were inversely correlated with OSI. There were no significant differences between "low-flux" and "high-flux" membranes in regard to oxidative stress parameters or PON-1 enzyme activities (all, P > 0.05). HD patients have increased oxidative stress and decreased serum PON-1 activities inversely correlated with oxidative stress. Membrane permeability seems to have no influence on oxidative stress parameters and PON-1 enzyme activities., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objectives: We investigated the correlation of serum paraoxonase-1 (PON-1) activity with coronary artery disease (CAD) in patients with metabolic syndrome (MetS)., Study Design: The study included 21 patients (mean age 55 ± 9 years) with MetS, stable angina pectoris, and angiographically shown CAD, 24 patients (mean age 51 ± 10 years) with MetS and angiographically normal coroner arteries, and 28 healthy controls (mean age 49 ± 12 years). Demographic and clinical characteristics, insulin levels, homeostasis model assessment of insulin resistance index, and PON-1 activity were assessed in all the groups. Severity of CAD was assessed using the Gensini score., Results: Paraoxonase-1 activity was significantly lower in patients with MetS compared to the control group (p=0.02). The two MetS groups with and without CAD exhibited similar characteristics in all the parameters including PON-1 activity (p>0.05). Univariate correlation analysis performed in MetS-CAD patients showed a significant negative correlation between the Gensini score and PON-1 activity (r=-0.48, p=0.02). The overall PON-1 activity of all the subjects showed no correlation with the parameters examined., Conclusion: Decreased PON-1 activity in patients with MetS compared to the control group suggests increased oxidative stress in MetS. Detection of similar PON-1 activity levels in MetS groups with and without CAD suggests that disturbance of oxidative-antioxidative balance occurs before the development of CAD. The negative correlation between the Gensini score and PON-1 activity implies that decreased PON-1 activity may be one of the etiologic causes of atherosclerotic progress in MetS.

Objectives: We aimed to evaluate the oxidant/antioxidant status of thyroid tissue in patients with multinodular goiter, papillary carcinoma and to compare with their nonpathologic tissues., Methods: We studied 41 patients with multinodular goiter who underwent surgical treatment. The patients were divided into three groups according to clinical diagnosis. Malondialdehyde, selenium, total superoxide dismutase and glutathione peroxidase of thyroid tissue samples were determined in 14 toxic multinodular goiters, 18 non-toxic multinodular goiters, and 9 papillary carcinomas., Result: Superoxide dismutase and glutathione peroxidase and selenium were found lower but malondialdehyde was higher in both nodule and cancerous tissues compared with those of control ones. The level of malondialdehyde in non-toxic multinodular goiters group was higher than toxic multinodular goiters group in nodule tissues., Conclusions: It can be stated that the lipid peroxidation is increased and enzymatic free radical defense system was significantly impaired in patients with both multinodular goiters and papillary carcinomas., (2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of testosterone replacement therapy on bladder functions and smooth muscle/collagen content in orchidectomized orchiectomized mature male rats., Methods: The study included 25 mature male Sprague-Dawley rats divided into 3 groups. After bilateral orchiectomy, 8 rats received intramuscular saline injection, as a control group, and 8 rats received intramuscular injection of testosterone undecanoate 100 mg/kg as a treatment group. The sham group had 9 rats. Urodynamic studies were performed in all groups, before and after the study. The rats were killed after 60 days, and cystometric findings and smooth muscle/collagen ratio of the bladders were compared between the groups., Results: From the beginning to the end of the experiment, mean maximal bladder capacity increased 46.61% +/- 20.82 in the testosterone treatment group, while decreased 38.91% +/- 17.83 in control group, revealing a significant difference (P = .002). Smooth muscle/collagen ratio was significantly higher in the testosterone treatment group (1.53 +/- .34) than in the control group (1.05 +/- .32), (P = .01)., Conclusions: This study showed that bladder capacity and smooth muscle/collagen content improved with testosterone therapy in orchiectomized rats. Therefore, testosterone replacement therapy in late-onset hypogonadal men with urogenital dysfunction may have a positive role to improve bladder function by increasing bladder smooth muscle., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Studies have yielded conflicting results concerning flow cytometric lymphocyte analyses in patients with depression. Data about the effect of antidepressants on lymphocyte subsets are also contradictory. The aim of this study was to determine effects of venlafaxine versus fluoxetine on lymphocyte subsets in depressive patients., Methods: Sixty-nine patients diagnosed with major depressive disorder (MDD) according to DSM-IV and 36 healthy controls are included in the study. Sixty-nine patients were randomized to take fluoxetine (FLX) (n=33) or venlafaxine (VEN) (n=36). Serum lymphocyte subsets included CD3, CD4, CD8, CD16/56, CD19, CD45, Anti-HLA-DR which were measured by flow cytometric analyses at baseline and 6 weeks after the start of treatment. The severity of depression was evaluated with Hamilton rating scale for depression., Results: At baseline, patients with MDD had significantly lower CD16/56 ratio and higher CD45 ratio compared to the controls. Although numerically higher in the VEN treated patients, treatment response rates between the FLX (53%) and the VEN (75%) groups were not different statistically. CD45 values decreased significantly in the VEN group at the end of the 6 week treatment period whereas no difference was observed in the FLX group. By the 6th week, treatment responders showed a significantly higher CD16/56 ratio than non-responders. Baseline severity of depression and anxiety was positively correlated with baseline CD45 ratio and negatively correlated with baseline CD16/56 ratio. We did not observe consistent changes in the absolute number of circulating B or T cells, nor in the helper/inducer (CD4) or suppressor/cytotoxic (CD8) subsets., Conclusions: CD16/56 was lower in patients with MDD and increased in treatment responders at 6th week. CD45 ratio was higher in patients with MDD than healthy subjects; it decreased with antidepressant treatment and was positively correlated with the severity of depression. Antidepressant treatment contributes to immune regulation in patients with major depressive disorder., (Copyright 2009 Elsevier Inc. All rights reserved.)

In this study, the systemic hemodynamics induced by acute and chronic cadmium (Cd+2) intoxication in the cardiovascular system of rats using thoracic electrical bioimpedance were examined and the acute and chronic effects of Cd+2 intoxication on the activities of antioxidant enzymes and malondialdehyde (MDA) were compared. Also, in this study, ultrastructural changes in the heart and aorta of rats were evaluated. Thirty-eight male Wistar albino rats were randomly divided into control, acute, and chronic groups. Chronic group was administered by oral gavage an aqueous solution of CdCl2 for 60 days, at dose of 15 mg Cd+2/kg/day. Acute group was administered by oral gavage an aqueous solution of CdCl2 with a single dose of 15 mg Cd+2/kg. Cadmium increased the stroke volume and cardiac output of rats in the chronic group, but did not change the heart rate significantly. Antioxidant enzymes activities and MDA level significantly increased in the chronic group. In ultrastructural examination, there were widespread degenerative changes in heart muscle cells of the chronic group but endothelial cells and smooth muscle cells in the aorta tissue samples had normal morphological features in all groups. All of the findings indicate that Cd+2 toxication can cause deformation in heart muscle cells due to an increase in free radicals and lipid peroxidation. Also, this study has confirmed that a long-term-Cd+2 exposure increased stroke volume (SV) and cardiac output (CO), but did not change the heart rate (HR).

In this study, Cadmium (Cd) genotoxicity was investigated in both bone marrow and peripheral blood treatment using rat micronucleus technique as genotoxicity test at acute and chronic treatment in the same animals. This study evaluated the frequency of micronuclei in the peripheral blood and bone marrow of male rats treated with unique cadmium dose (15 mg/kg. body w/day) by gavage for 60 days and acute treatment for 24 h, respectively. Mitomycin C (MMC) 2 mg/kg body wt was used as a positive control. This study shows that cadmium chloride treatment significantly induced the frequency of micronucleus in polychromatic erythrocytes in both tibia bone marrow and peripheral blood (p < 0.001, p < 0.01, respectively). This increase in micronucleus frequency shows that cadmium has a genotoxic effect on bone marrow and peripheral blood at this level. Also, in order to determine cytotoxicity in bone marrow and peripheral blood, the ratio of polychromatic erythrocytes to normochromatic erythrocytes was calculated in bone marrow and peripheral blood. Cd treatment decreased this ratio in only bone marrow. The results of this study demonstrate that Cd has both toxic and genotoxic potential in bone marrow and only genotoxic potential in peripheral blood. There is a significant difference between the control group and exposed group, including acute and chronic treatment for blood Cd level (p < 0.001). No significant difference was found between acute and chronic exposure group (p > 0.05).

This study investigated time-dependent variations in the activities of adenosine deaminase (ADA), an adenosine-metabolizing enzyme, and myeloperoxidase (MPO), an oxidation reaction-catalyzing enzyme, in control and streptozotocin (STZ)-induced diabetic rat liver. The animals were sacrificed at six different times of day (1, 5, 9, 13, 17 and 21 hours after lights on - HALO). The hepatic activity of ADA did not change depending on the STZ treatment whereas MPO activity was significantly higher in the diabetics than in the controls. Hepatic ADA activity was dependent on the time of sacrifice with the lowest activity at 21 HALO and the highest activity at 5 HALO. Both enzyme activities failed to show any significant interaction between STZ treatment and time of sacrifice, which means that diabetes does not influence the 24 h pattern of these activities. Since MPO, a heme protein localized in the leukocytes, is involved in the killing of microorganisms, increased MPO activity in diabetic rat liver may reflect leukocyte infiltration secondary to diabetes. A reduction in ADA activity during the dark (activity/feeding) period will presumably lead to high concentrations of adenosine in the liver, possibly contributing to changes in some metabolic processes, such as glycogen turnover and oxygen supply.

Neutrophil infiltration has been reported to play an important role in spinal cord injury (SCI). In addition to their cardioprotective effects, beta-blockers have been found to have neuroprotective effects on the central nervous system, but their effect on SCI has not yet been studied. In the current study, we investigated the effect of metoprolol on myeloperoxidase (MPO) activity, a marker of neutrophil activation, in the spinal cord after experimental SCI in rats. Rats were divided into six groups: controls received only laminectomy and spinal cord samples were taken immediately; the sham operated group received laminectomy, and spinal cord samples were taken 4h after laminectomy; the trauma only group underwent a 50g/cm contusion injury but received no medication; and three other groups underwent trauma as for the trauma group, and received 30mg/kg methylprednisolone, 1mg/kg metoprolol, or 1mL saline, respectively. All the medications were given intraperitoneally as single doses, immediately after trauma. Spinal cord samples were taken 4h after trauma and studied for MPO activity. The results showed that tissue MPO activity increased after injury. Both metoprolol and methylprednisolone treatments decreased MPO activity, indicating a reduction in neutrophil infiltration in damaged tissue. The effect of metoprolol on MPO activity was found to be similar to methylprednisolone. In view of these data, we conclude that metoprolol may be effective in protecting rat spinal cord from secondary injury.

Objective: To investigate the effects of genistein on reperfusion injury in a rat ovarian torsion-detorsion model., Design: Controlled experimental study., Setting: University animal research laboratory., Subject(s): Thirty-two Wistar-Albino rats., Intervention(s): The rats were divided into four groups. Sham operation was performed in group I. In group II, 5 mg/kg genistein was given intraperitoneally (IP) during laparotomy, and right ovaries were removed 4 hours later. In group III, right ovaries were subjected to 4 hours of adnexal ischemia by use of vascular clips, and after ischemic insult, 4 hours of reperfusion was maintained by removing the clips. In group IV, after the ischemic period, 5 mg/kg genistein was given IP, and 4 hours of reperfusion was maintained. Right ovaries were surgically removed at the end of the procedure in each group., Main Outcome Measure(s): Ovarian histopathologic findings were scored and compared among study groups. Serum and ovarian tissue malondialdehyde (MDA), glutathione peroxidase, and superoxide dismutase, levels were measured., Result(s): Ovarian tissue damage scores were significantly different among groups and were seen to correlate with ovarian tissue MDA levels. Genistein significantly decreased the tissue damage scores, ovarian tissue MDA levels, and serum MDA levels., Conclusion(s): Genistein attenuates ischemia-reperfusion injury in rat adnexal torsion-detorsion model.

In the present study, we report the effect of vitamin A (Vit A, retinol palpitate) on kidney lipid peroxidation and 3-nitrotyrosine (3-NT) levels induced after Escherichia coli administration to guinea pigs. Vit A was administrated intraperitoneally (i.p.) to guinea pigs at a dose 15,000 IU/kg per day for 7 days prior to E. coli injection. On day 8, the animals were injected i.p. with E. coli dosed at 12 x10(9) colony forming units per kilogram. Kidneys were collected 6 h after administration of E. coli. Malondialdehyde (MDA) as a lipid peroxidation product, and 3-NT levels were measured by reverse phase high-performance liquid chromatography. There was a significant increase in MDA and 3-NT levels in lipopolysaccaharide-induced group (p<0.001). 3-NT was not detectable in kidney of normal control animals. However, Vit A administration prior to E. coli injection prevented 3-NT formation but did not prevent the rice in MDA level of kidney (p<0.001). Vit A alone did not alter the MDA level in the kidney of the control group.

The aim of this study was to evaluate the effects of Escherichia coli-derived lipopolysaccharide on guinea pig kidney by measuring the energy charge ratio and 3-nitrotyrosine levels. In addition the possible protective role of melatonin against lipopolysaccharide-mediated peroxynitrite formation and energy depletion of kidney was determined. Guinea pigs were either pretreated with melatonin or saline (for the control) followed by intraperitoneal administration of E. coli. Six hours after the administration of E. coli, guinea pig kidney ATP, ADP, AMP and 3-nitrotyrosine levels were measured by reverse-phase high performance liquid chromatography. There was a significant increase in the formation of 3-nitrotyrosine and decrease in energy charge in the endotoxin-induced group. However melatonin administration prevented 3-nitrotyrosine formation while failing to prevent or restore changes in the energy charge ratio of the kidney., (Copyright 2004 John Wiley & Sons, Ltd.)

This study was designed to investigate the effect of selenium on ipsilateral and contralateral testicular damage after unilateral testicular torsion/detorsion (T/D). Thirty-two male rats were divided into four groups, each containing eight rats. Torsion was created by rotating the right testis 720 degrees in a clockwise direction. Group 1 underwent sham operation to determine basal values for biochemical and histopathological evaluation. Sham operation was performed in group 2, and sodium selenate (0.2 mg/kg) was given intraperitoneally. Group 3 served as a T/D group, receiving 4-h torsion and 4-h detorsion. Similarly, in group 4 sodium selenate (0.2 mg/kg) was injected intraperitoneally 20 min before detorsion. Bilateral orchiectomies were performed for measurement of tissue malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities and histopathologic examination. The results were compared statistically. The highest MDA and the lowest SOD values were determined in both testes in group 3. There were statistically significant differences in MDA levels and SOD activities in group 3 compared with group 4. Specimens from group 3 had a significantly greater histologic injury than other groups. These results suggest that ischemia-reperfusion injury occurred in both testes after unilateral testicular T/D and that selenium administration before detorsion prevents reperfusion injury in testicular torsion.

Endotoxins (lipopolysaccharides; LPS) are known to cause multiple organ failure, including renal dysfunction. LPS triggers the synthesis and release of cytokines and the vasodilator nitric oxide (NO*). A major contributor to the increase in NO* production is LPS-stimulated expression of inducible nitric oxide synthase (iNOS). This occurs in vasculature and most organs including the kidney. During endotoxemia, NO* and superoxide react spontaneously to form the potent and versatile oxidant peroxynitrite (ONOO-) and the formation of 3-nitrotyrosine (nTyr)-protein adducts is a reliable biomarker of ONOO- generation. Therefore, the present study was aimed at investigating the role of endogenous nitric oxide in regulating Na+,K(+)-ATPase activity in the kidney, and at investigating the possible contribution of reactive nitrogen species (RNS) by measuring of iNOS activity. In addition, the present study was aimed at investigating the relationship between nTyr formation with iNOS and Na+,K(+)-ATPase activities. Previously in our study, nTyr was not detectable in kidney of normal control animals but was detected markedly in LPS exposed animals. In this study, kidney Na+,K(+)-ATPase activity were maximally inhibited 6 h after LPS injection (P:0.000) and LPS treatment significantly increased iNOS activity of kidney (P:0.000). The regression analysis revealed a very close correlation between Na+,K(+)-ATPase activity and nTyr levels of LPS treated animals (r = -0.868, P = 0.001). Na+,K(+)-ATPase activity were also negatively correlated with iNOS activity (r = -0.877, P = 0.001) in inflamed kidney. These data suggest that NO* and ONOO- contribute to the development of oxidant injury. Furthermore, the source of NO* may be iNOS. iNOS are expressed by the kidney, and their activity may increase following LPS administration. In addition, NO* and ONOO- formation inhibited Na+,K(+)-ATPase activity. This results also have strongly suggested that bacterial LPS disturbs activity of membrane Na+,K(+)-ATPase that may be an important component leading to the pathological consequences such as renal dysfunction in which the production of RNS are increased as in the case of LPS challenge.

The aim of this study was to investigate the effect of desferrioxamine on peroxynitrite-mediated damage in erythrocytes by measuring the 3-nitrotyrosine level and glutathione peroxidase and Na(+)-K(+) ATPase activities in vitro. 3-Nitrotyrosine levels were determined by HPLC; glutathione peroxidase and Na(+)-K(+) ATPase activities were measured by spectrophotometry. Peroxynitrite increased the 3-nitrotyrosine level but decreased both enzyme activities. In the presence of desferrioxamine, glutathione peroxidase activity was increased with a decrease in the 3-nitrotyrosine level. Desferrioxamine was found to possess an important antioxidant activity as assessed in an in vitro system, reducing protein nitration, restoring enzyme activities and maintaining erythrocyte membrane integrity., (Copyright 2004 John Wiley & Sons, Ltd.)

In animal models of endotoxin, the excess production of NO and the reactive nitrogen species (RNS), are potent oxidant and nitrating agents, lead to lipid peroxidation, apoptosis, tissue dysfunction and injury and inactivate enzymes in many cell types. Although liver functions are well known to deteriorate following bacterial infection, the underlying specific mechanism(s) remain a matter of considerable debate. Therefore, the aim of the present study was to determine the in vivo effect of bacterial lipopolysaccharides (LPS) on Na+,K+-ATPase activity of guinea pig liver, and to investigate the possible contribution of RNS by measuring of iNOS activity and 3-nitrotyrosine (nTyr) levels. Liver Na+,K+-ATPase activity were maximally inhibited 6 h after LPS injection (p < 0.001 ). nTyr was not detectable in liver of normal control animals, but was detected markedly in LPS exposed animals. LPS treatment significantly increased iNOS activity of liver (p < 0.001). The regression analysis revealed a very close correlation between Na+,K+-ATPase activity and nTyr levels of LPS treated animals (r = -0.863, p < 0.001). Na+, K+-ATPase activity were also negatively correlated with iNOS activity (r = -0.823, p < 0.003) in inflamed tissues. Our results have strongly suggested that bacterial LPS disturbs activity of membrane Na+,K+-ATPase that may be an important component leading to the pathological consequences such as hepatocyte cell loss and dysfunction in which the production of RNS are increased as in the case of LPS challenge.

Objective: To assess the relationship of grip strength to site-specific bone mineral density of the metacarpal bone and also axial bone mineral density. The bone mineral density of the lumbar spine, femoral neck and the nondominant hand were measured by DEXA., Subjects: A total of 187 postmenopausal women were included in the study. Of the patients, 102 were osteoporotic, and 85 were not osteoporotic and served as control subjects., Methods: Grip strength of the nondominant hand was measured by hand-held dynamometer. Skinfold thickness of the nondominant hand was measured by a caliper (Holstain). Biochemical markers of bone turnover and other osteoporosis-related variables were also measured., Results: There was a statistically significant difference between groups regarding bone mineral density of the lumbar, femoral (neck) and hand regions and the grip strength (P < .05). Hand bone mineral density (BMD) was found to be correlated with bone mineral density of the lumbar and femoral (neck) regions in osteoporotic patients. Grip strength was correlated positively with the BMD of the nondominant hand. Grip strength was correlated negatively with age and years since menopause. Grip strength was also correlated positively with femoral neck BMD., Conclusion: The study provides support for a site-specific and also systemic relationship between muscle and bone. Grip strength is also a predictor of hand bone mineral density.