Melatonin Prevents UVB-Induced Skin Photoaging by Inhibiting Oxidative Damage and MMP Expression through JNK/AP-1 Signaling Pathway in Human Dermal Fibroblasts.

Exposure to ultraviolet (UV) irradiation causes damage to the skin and induces photoaging. UV irradiation stimulates production of reactive oxygen/nitrogen species, which results in activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) in fibroblasts. MAPKs are responsible for activation of activator protein-1 (AP-1), which subsequently upregulates expression of matrix metalloproteinases (MMPs). Melatonin is a potent free radical scavenger which is known to have photoprotective effects. The aim of this study is to investigate the underlying molecular mechanisms for the photoprotective effects of melatonin in UVB-irradiated primary human dermal fibroblasts (HDFs) in terms of EGFR activation, oxidative/nitrosative damage, JNK/AP-1 activation, MMP activities, and the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and type I procollagen (PIP-C). In this study, HDFs were pretreated with 1 µM of melatonin and then irradiated with 0.1 J/cm2 of UVB. Changes in the molecules were analyzed at different time points. Melatonin inhibited UVB-induced oxidative/nitrosative stress damage by reducing malondialdehyde, the ratio of oxidized/reduced glutathione, and nitrotyrosine. Melatonin downregulated UV-induced activation of EGFR and the JNK/AP-1 signaling pathway. UVB-induced activities of MMP-1 and MMP-3 were decreased and levels of TIMP-1 and PIP-C were increased by melatonin. These findings suggest that melatonin can protect against the adverse effects of UVB radiation by inhibiting MMP-1 and MMP-3 activity and increasing TIMP-1 and PIP-C levels, probably through the suppression of oxidative/nitrosative damage, EGFR, and JNK/AP-1 activation in HDFs.

Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration.

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

Melatonin attenuates the detrimental effects of UVA irradiation in human dermal fibroblasts by suppressing oxidative damage and MAPK/AP-1 signal pathway in vitro.

BACKGROUND: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen-activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP-1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures. OBJECTIVES: In this study, we investigated the effects of melatonin on UVA-irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time-dependent manner which have not been clearly elucidated yet. METHODS: To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub-cytotoxic dosage (20 J/cm2 ) after pretreatment with melatonin (1 µmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points. RESULTS: Our results clearly show that melatonin decreases UVA-induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP-1 signal transduction pathway and production of matrix metalloproteinases in a time-dependent manner. CONCLUSION: Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation.

Serum brain-derived neurotrophic factor levels in treatment-naïve boys with attention-deficit/hyperactivity disorder treated with methylphenidate: an 8-week, observational pretest-posttest study.

Brain-derived neurotrophic factor (BDNF) is an important neurotrophin in the brain that modulates dopaminergic neurons. In this study, we aimed to investigate the changes in serum BDNF levels of children with attention-deficit/hyperactivity disorder (ADHD) in response to OROS methylphenidate treatment. We also aimed to determine whether there were any pre-post-differences between ADHD subtypes and comorbid psychiatric disorders in serum BDNF levels. Fifty male children with ADHD and 50 male healthy controls within the age range of 6-12 years were recruited to the study. The psychiatric diagnoses were determined by applying a structured interview with Kiddie schedule for affective disorders and schizophrenia for school-age children-present and lifetime version. The symptom severity of ADHD was measured using the Clinical Global Impression ADHD Severity Scale (CGI-S). Physicians completed Du Paul ADHD questionnaires. The levels of serum BDNF were assessed before and after 8 weeks of treatment with effective dosages of OROS methylphenidate. In the present study, the mean serum BDNF levels of boys with ADHD and of the healthy controls were 2626.33 ± 1528.05 and 2989.11 ± 1420.08 pg/mL, respectively. Although there were no statistically significant difference between the ADHD group and healthy controls at baseline (p = 0.22), the increase of serum BDNF was statistically significant from baseline to endpoint in the ADHD group (p = 0.04). The mean serum BDNF levels at baseline and endpoint of the ADHD group were 2626.33 ± 1528.05 and 3255.80 ± 1908.79 pg/mL, respectively. The serum BDNF levels of ADHD-inattentive subtype were significantly lower at baseline (p = 0.02), whereas BDNF levels post-treatment showed no significant difference. The increase of serum BDNF levels with methylphenidate treatment after 8 weeks was significantly higher in the inattentive group (p = 0.005). The increase of serum BDNF levels with methylphenidate treatment after 8 weeks in boys with ADHD may support the potential role of BDNF in the pathophysiology of ADHD. The role of BDNF in ADHD subtypes in particular should be evaluated with further, larger studies.

Serum Brain-derived Neurotrophic Factor Levels among Euthymic Adolescents with Bipolar Disorder Type I.

INTRODUCTION: Bipolar disorder (BD) has been increasingly associated with abnormalities in neuroplasticity and cellular resilience in brain regions that are involved in mood and that affect regulation. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that regulates neuroplasticity. The aims of the current study were to compare serum BDNF levels in euthymic adolescents with BD type I with those in controls and to investigate the relationship between clinical variables and serum BDNF levels in adolescents with BD type I. METHODS: Twenty-five adolescents diagnosed with BD type I and 17 healthy control subjects within the age range of 15-19 years were recruited. Diagnoses were made by two experienced research clinicians using the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and the affective module of Washington University in St. Louis Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia-Present State and Lifetime. Blood samples were taken during euthymia, which was defined as Young Mania Rating Scale and Hamilton Depression Rating Scale scores below 7. RESULTS: The comparison of BDNF serum levels between the case and healthy control groups revealed no significant differences. In the case group, BDNF levels were significantly lower in patients being currently treated with lithium. CONCLUSION: Similar to normal BDNF levels in adult patients with BD, the normal BDNF serum levels that we found in the euthymic state in adolescents and early adulthood may be related to the developmental brain stage in our study group. It may also show a common neurobiological basis of pediatric and adult BD. Further investigations evaluating BDNF levels in different mood states could help identify the role of BDNF in the underlying pathophysiology of BD.

Correlations between amygdala volumes and serum levels of BDNF and NGF as a neurobiological markerin adolescents with bipolar disorder.

BACKGROUND: The amygdala is repeatedly implicated as a critical component of the neurocircuitry regulating emotional valence. Studies have frequently reported reduced amygdala volumes in children and adolescents with bipolar disorder (BD). Brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play critical roles in growth, differentiation, maintenance, and synaptic plasticity of neuronal systems in adolescent brain development. The aim of the present study was to assess amygdala volumesand its correlation with serum levels of NGF and BDNF in euthymic adolescents with BD and healthy controls. METHODS: Using structural MRI, we compared the amygdala volumes of 30 euthymic subjects with BD with 23 healthy control subjects aged between 13 and 19 years during a naturalistic clinical follow-up. The boundaries of the amygdala were outlined manually. Serum BDNF and NGF levels were measured using sandwich-ELISA and compared between the study groups. RESULTS: The right or left amygdala volume did not differ between the study groups.The right and left amygdala volumes were highly correlated with levels of BDNF in the combined BD group and the valproate-treated group.Both R and L amygdala volumes were correlated with BDNF levels in healthy controls. The left amygdala volumes were correlated with BDNF levels in the lithium-treated group. LIMITATIONS: This cross-sectional study cannot inform longitudinal changes in brain structure. Further studies with larger sample sizes are needed to improve reliability. CONCLUSIONS: The correlations between amygdala volumes and BDNF levels might be an early neuromarker for diagnosis and/or treatment response in adolescents with BD.

Decreased right hippocampal volumes and neuroprogression markers in adolescents with bipolar disorder.

OBJECTIVES: The aim of the present study was to assess differences and correlations between the hippocampal volumes (HCVs), serum nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in adolescents with bipolar disorder (BP) compared to healthy controls. METHODS: Using structural magnetic resonance imaging, we compared HCVs of 30 patients with euthymic BP who were already enrolled in a naturalistic clinical follow-up. For comparison, we enrolled 23 healthy controls between the ages of 13 and 19. The boundaries of the hippocampus were outlined manually. The BDNF and NGF serum levels were measured with the sandwich ELISA. RESULTS: The groups did not differ in the right or left HCVs or in the NGF or BDNF serum levels. However, negative correlations were found between the right HCVs and the duration of the disorder and medication and positive correlations were found between the duration of the medications and the NGF and BDNF levels in the patient group. Additionally, positive correlations were found between the follow-up period and left normalized HCVs in both the BP and lithium-treated groups. CONCLUSIONS: The right HCVs may vary with illness duration and the medication used to treat BP; NGF and BDNF levels may be affected by long-term usage. Further research is needed to determine whether these variables and their structural correlates are associated with clinical or functional differences between adolescents with BP and healthy controls.

A Preliminary Observation of Increased Glial Cell Line-Derived Neurotrophic Factor in Manic Switch due to Electroconvulsive Treatment in Depressive Patients.

OBJECTIVE: Neurotrophic factors are known to be involved in the pathogenesis of mood disorders. However, the precise neurobiology underlying relapse into depression or switch to mania under antidepressant treatment is not fully understood. Evidence suggests the role of neuroplasticity in these processes. METHOD: Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor (GDNF) serum levels were measured concomitantly during electroconvulsive treatment (ECT) in 30 depressive patients (25 patients with unipolar, 5 with bipolar depression), including those who relapsed into depression (n = 6) or switched to mania (n = 3) within 1 to 4 weeks after the end of the ECT, and in 33 healthy volunteers. RESULTS: Despite significant decrease in depression scores, the levels of brain-derived neurotrophic factor did not significantly change during the ECT, also in the patients who relapsed into depression or switched to mania. However, GDNF levels were lower in the ECT responders compared with pre-ECT levels (z = -2.203; P = 0.01) and increased in manic switch compared with the ECT responders (z = -2.761; P = 0.001) (Cohen d = -1.75; effect size r = -0.66) and healthy controls as well (P = 0.044). CONCLUSIONS: Our data suggest the role of GDNF in manic switch and the involvement of glial system in the pathogenesis of mood disorders.

Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. METHOD: BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. RESULTS: Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. LIMITATIONS: Small sample size in different episodes and drug-free patients was the limitation of thestudy. CONCLUSION: Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia.

Erythrocyte deformability and oxidative stress in inflammatory bowel disease.

BACKGROUND: Oxidative stress and reduced microvascular flow are important factors in the pathogenesis of inflammatory bowel disease (IBD). The increased oxidative stress reduces the erythrocyte deformability. However, in IBD, there are no studies in the literature which evaluate erythrocyte deformability. AIMS: In our study, we investigated the effect of oxidative stress and erythrocyte deformability in IBD. METHODS: Forty-three patients with active IBD, 48 patients with inactive IBD and 45 healthy controls were included. The erytrocyte deformability, malonyldialdehyde levels, glutation peroxidase and sulfhydryl levels were measured in peripheral venous blood samples. RESULTS: Erytrocyte malonyldialdehyde levels in both active and inactive IBD were significantly increased compared with control groups. Plasma glutation peroxidase levels did not show statistically significant difference between all groups. The decreased plasma sulfhydryl levels in active IBD were statistically significant compared with both the inactive IBD and the control group, but plasma sulfhydryl levels in inactive IBD group did not show statistically significant differences when compared with the control group. Elongation index values in both active and inactive IBD increased significantly compared with the control group. Statistically significant correlations were not found between the elongation index and glutation peroxidase, malonyldialdehyde, sulfhydryl levels in all groups. CONCLUSIONS: Our study is the first to evaluate the erythrocyte deformability in IBD. In our study, increased erytrocyte malonyldialdehyde levels and decreased plasma sulfhydryl levels manifested the role of oxidative stress in the pathogenesis of the disease. It is thought that the increased erythrocyte malonyldialdehyde values cause the reduction in erythrocyte deformability.

Special-study modules in a problem-based learning medical curriculum: an innovative laboratory research practice supporting introduction to research methodology in the undergraduate curriculum.

We describe the organization of wet-lab special-study modules (SSMs) in the Central Research Laboratory of Dokuz Eylül Medical School, Izmir, Turkey with the aim of discussing the scientific, laboratory, and pedagogical aspects of this educational activity. A general introduction to the planning and functioning of these SSMs is given, along with specific examples. The wet-lab SSMs incorporate several innovative pedagogies: problem-based learning, research-based learning, practical laboratory education, team-based learning, and project-based learning. Oral and written evaluations show that the students find this activity rewarding. The wet-lab SSM model applied in the Research-Lab of Dokuz Eylül School of Medicine represents a format which is effective in training the students in research methodology, practical laboratory work, and independent learning.

The combination of bortezomib and resveratrol may prevent muscle wasting in diabetes.

Hypercatabolic syndrome is a biochemical state characterized by a imbalance between catabolism and anabolism in favor of catabolism. Diabetes is an example of hypercatabolic syndrome with presence of decreased insulin level or impaired insulin signaling besides increased inflammatory cytokines. One of the significant outcomes of this state is accelerated protein degradation and muscle wasting. Increased ubiquitin-proteasomal system activity is the major responsible for the muscle wasting. Increase in expression and activities of proteasomal proteins in diabetes had been determined. NF-κB transcription factor mediated inflammation and oxidative stress accompanies proteasomal activity increase. Oxidative stress continuously produces substrate for proteasomes by causing protein oxidation. An intervention that inhibits proteasomal activity, suppressing inflammation and oxidative stress may form a solution in order to prevent muscle wasting. Therefore, I am considering that the combined use of bortezomib, a proteasome inhibitor and an anti-inflammatory with resveratrol, an antioxidant and anti-inflammatory, could prevent diabetes induced muscle wasting. This combination may be a novel therapeutic approach for muscle wasting.

Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats.

Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CCI-induced peripheral nerve pathology. Ghrelin, a novel identified gastric peptide, has been shown to have antinociceptive activity and also anti-inflammatory properties by decreasing proinflammatory cytokines. Therefore, the aim of the present study was to investigate the effects of ghrelin on the CCI and its relationship with proinflammatory cytokines in rats. Wistar rats underwent sciatic nerve ligation to induce CCI fallowed by repeated ghrelin administrations (50 and 100microg/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-alpha, IL-1beta and IL-6 were measured in blood and spinal cord. The changes of sciatic nerve was assessed histologically by both light and electron microscopy. Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-alpha and IL-1beta levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-alpha and IL-1beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain.

Increased hexosaminidase activity in antipsychotic-induced extrapyramidal side effects: possible association with higher occurrence in bipolar disorder patients.

Dystonic movements and Parkinsonism are frequently seen in gangliosidoses and these conditions have been reported to modify dopaminergic plasticity. We investigated whether the activity of hexosaminidase, a type-two ganglioside (GM2) degrading enzyme, correlates with drug-induced extrapyramidal system (EPS) side effects in psychiatric patients. We compared hexosaminidase activity in the lymphocytes of 29 EPS-positive patients, 13 EPS-negative patients, and 30 healthy volunteers. The activities of A and B isoforms of hexosaminidase were higher in EPS-positive patients than EPS-negative patients and healthy controls. Multivariate analysis suggested an interaction with increased B isoform activity and EPS side effects in female bipolar disorder patients. Higher levels of hexosaminidase enzyme activity may explain the frequent occurrence of antipsychotic-induced extrapyramidal side effects in mood disorder patients.

Does antioxidant supplementation alter the effects of acute exercise on erythrocyte aggregation, deformability and endothelium adhesion in untrained rats?

This study aimed to determine whether high-dose antioxidant supplementation had an impact on the acute exercise effects related to erythrocyte membrane mechanics. Experimental animals (n=32) were divided into four groups as control, exercised, supplemented, and supplemented + exercise. Four-week antioxidant supplementation (vitamin C, vitamin E, and zinc) was applied to experimental animals. Following acute exercise on a motor-driven rodent treadmill, erythrocyte aggregation and deformability, erythrocyte adhesion to endothelial cells, superoxide dismutase (SOD), and glutathione peroxidase activities of the erythrocytes were analyzed. In both supplemented and non-supplemented exercised groups, there was a significant decrease in SOD activities and erythrocyte aggregation, and an increase in adhesion to endothelial cell although there was no change on erythrocyte deformability. There were no differences in the responses to the exercise of supplemented and nonsupplemented rats. The data suggested that high-dose antioxidant supplementation did not alter the effects of acute exercise on erythrocyte membrane mechanics.

Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats.

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 microg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA-Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA-Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA-Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA.

In vitro effects of high glucose concentrations on membrane protein oxidation, G-actin and deformability of human erythrocytes.

The object of this study was to examine the effect of elevated in vitro glucose concentrations on protein modification and functional changes in human erythrocytes. Groups were exposed to 5-45 mM glucose concentrations. The time effect of any changes was also evaluated. In erythrocyte ghosts, protein glycation and oxidation were evaluated using spectrophotometric methods. G-actin was measured by a DNase I inhibition assay in cell lysates. Erythrocyte deformability was assessed using a cell transit analyser. At 24 h, a significant protein oxidation (at 25 and 45 mM glucose; p < 0.05), and G-actin increase was observed for all concentrations (p < 0.05). At 48 h, a significant increase in glycation (25 and 45 mM glucose; p < 0.05), protein oxidation (p < 0.05), and G-actin (p < 0.05) was observed in all groups. A significant positive correlation was observed between glucose /protein oxidation, glucose/G-actin and protein oxidation/G-actin at 24 and 48 h. Our findings show that the oxidative effect of glucose on erythrocytes depends on concentration and incubation time. We also present the first evidence of increased G-actin in human erythrocytes exposed to high glucose concentrations as a diabetes model.

Effect of melatonin cotreatment against kainic acid on coenzyme Q10, lipid peroxidation and Trx mRNA in rat hippocampus.

Oxidative stress is a likely molecular mechanism in the neurotoxicity of kainic acid (KA), an excitotoxic substance. The aim of this report was to assess the effect of melatonin co-treatment against KA by measuring the levels of Coenzyme Q10 (CoQ 10), lipid peroxidation (LPO), and Thioredoxin (Trx) mRNA in the rat hippocampus. The male rats were divided into three groups as saline, KA treatment (15 mg/kg), and KA plus melatonin (20 mg/kg). The levels of LPO and CoQ10 were determined by high pressure liquid chromatography (HPLC) consisting of fluorescence and electro-chemical detectors, respectively. The expression of the Trx gene was quantified using reverse transcription followed by real-time polymerase chain reaction (RT-PCR). The results show that the level of LPO increased although the level of CoQ10 decreased both in homogenates and mitochondria in KA-treated rats However, melatonin co-treatment attenuated the level of LPO and partially restored the level of CoQ10. Melatonin co-treatment against KA did not affect the regulation of Trx. Finally, in the context of the decreased LPO and the increased CoQ10, the results suggest that melatonin may be protective against central nervous system pathologies involving excitotoxicity or where oxidative damage may contribute to mitochondrial dysfunction.

Increased inositol-monophosphatase activity by lithium treatment in bipolar patients.

Inhibition of inositol monophosphatase (IMPase) enzyme is the target mechanism of action of lithium. However, increased activity of mRNA levels by lithium has been reported. These two diverse effects were shown after relatively short periods of lithium administration. The aim of this study was to observe the effect of prolonged use of lithium on IMPase activity. The authors investigated IMPase activities in fresh erythrocytes and leukocytes in 63 bipolar patients (42 euthymic, 8 depressive, 13 manic episodes) and 16 control subjects. We found that erythrocyte IMPase activity was higher in lithium treated euthymic patients than non-lithium treated patients. The duration of lithium use was positively correlated with leukocyte IMPase activity. Increased IMPase activity by chronic lithium use suggests an up-regulation of the enzyme activity.