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Modafinil is generally known as a drug with low addiction potential. There are few case reports in the literature demonstrating that Modafinil, stated being capable of diminishing symptoms of attention deficit/hyperactivity disorder (ADHD), causes addiction. In the present article a Modafinil addicted ADHD case, consuming usurious doses (5,000 mg/per day) of Modafinil is presented. The case presented to our psychiatry outpatient clinic due to: requirement of in taking high dose Modafinil in order to achieve the initial effects, difficulty in obtaining the drug, irritability, anxiousness, sleep irregularities, fatigue and unpleasant vivid dreams when he did not use the drug. It was realized that the patient, himself increased doses of Modafinil incrementally, in order to keep its effects on attention symptoms at the same level. It has to be kept in mind that ADHD patients can develop Modafinil addiction. It is necessary to carry out systemic studies on this subject.

Modafinil is generally known as a drug with low addiction potential. There are few case reports in the literature demonstrating that Modafinil, stated being capable of diminishing symptoms of attention deficit/hyperactivity disorder (ADHD), causes addiction. In the present article a Modafinil addicted ADHD case, consuming usurious doses (5,000 mg/per day) of Modafinil is presented. The case presented to our psychiatry outpatient clinic due to: requirement of in taking high dose Modafinil in order to achieve the initial effects, difficulty in obtaining the drug, irritability, anxiousness, sleep irregularities, fatigue and unpleasant vivid dreams when he did not use the drug. It was realized that the patient, himself increased doses of Modafinil incrementally, in order to keep its effects on attention symptoms at the same level. It has to be kept in mind that ADHD patients can develop Modafinil addiction. It is necessary to carry out systemic studies on this subject.

Objective: We investigated the relationship between serum bilirubin levels and metabolic syndrome (MetS), and the longitudinal effects of baseline serum bilirubin concentrations on MetS in patients with schizophrenia spectrum disorders undergoing atypical antipsychotics. Methods: The sample of this study consisted of 131 patients with schizophrenia spectrum disorders. Waist circumference, blood pressure, and levels of triglycerides, high-density lipoprotein cholesterol, fasting glucose, and insulin were evaluated at baseline and at month six. Serum bilirubin levels were measured at baseline. Serum bilirubin levels of the patients with and without MetS criteria were compared. We also compared patients with high and low bilirubin levels (upper and lower 50th percentiles of serum bilirubin levels) in terms of MetS criteria, MetS frequency, and course of MetS. Results: Serum direct bilirubin levels were more consistently related to MetS and MetS-related variables. The waist circumference and triglyceride criteria for MetS were significantly related to low serum direct bilirubin at baseline; waist circumference and fasting glucose criteria, and insulin resistance were associated with low serum direct bilirubin at follow-up. MetS diagnosis and the presence of the waist circumference criterion were more frequent at the baseline and the follow-up in low bilirubin group. At the end of the follow-up period, the rate of reverse MetS was significantly higher in the high bilirubin group. Conclusion: Our results have suggested that serum direct bilirubin levels showed a more reliable and stable relationship with abdominal obesity for MetS components. in patients with schizophrenia spectrum disorders using antipsychotics. Further studies are required.

Objective Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Va166Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. Methods Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher's Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms. Results The GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes. Conclusion We found a positive association between the BDNF gene Va166Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Va166Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Va166Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.

The aim of the study was to determine the differences between expression levels of certain miRNAs, as their association with schizophrenia has been well presented in the literature, and to investigate their relation to treatment resistance in schizophrenic patients. Three groups were formed: 1) treatment resistant group, 2) treatment responsive group and 3) healthy control group. Expression levels of miRNAs from peripheric blood samples were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We investigated the roles of 29 schizophrenia-related miRNAs in schizophrenia treatment and their potentials to be considered as indicators. Among these miRNAs, only miR-181b-5p, miR-195-5p and miR-301a-3p expressions were found to be significantly different between the treatment-resistant group and the group responding well to the treatment miRNAs may cause resistance by silencing the receptor genes of the drugs used for schizophrenia treatment. miR-181b-5p, miR-195-5p and miR-301a-3p may be candidate indicators that can be used to reveal resistance against schizophrenia treatment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Ömer Başay,1 Burge Kabukcu Basay,1 Huseyin Alacam,2 Onder Ozturk,1 Ahmet Buber,1 Senay Gorucu Yilmaz,3 Yılmaz Kıroğlu,4 Mehmet Emin Erdal,5 Hasan Herken2 1Department of Child and Adolescent Psychiatry, Faculty of Medicine, Pamukkale University, Denizli, 2Department of Psychiatry, Faculty of Medicine, Pamukkale University, Denizli, 3Department of Nutrition and Dietetics, Faculty of Health Sciences, Gaziantep University, Gaziantep, 4Department of Radiology, School of Medicine, Pamukkale University, Denizli, 5Department of Medical Biology and Genetics, Faculty of Medicine, Mersin University, Mersin,Turkey Objective: To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD).Methods: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel 1H MRS when medication naïve and 30minutes after oral administration of 10mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses.Results: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>Aand rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016).Conclusion: Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings. Keywords: adult ADHD, magnetic resonance spectroscopy, N-acetylaspartate, genotype

Objective: Autism spectrum disorder (ASD) is characterized by deficits in social interaction, communication, restricted interests, and repetitive patterns of behavior. This study examined quality of life (QoL) and related clinical factors in children with ASD, compared to children with Attention Deficit Hyperactivity Disorder (ADHD), children with asthma, and healthy controls (HC). Methods: QoL was assessed by the Pediatric Quality of Life Inventory 4.0 (PedsQLTM 4.0). Additionally, parents of the children provided sociodemographic information and filled out an evaluation questionnaire, child behavior check list (CBCL), and Turgay DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S). Results: The physical health, psychosocial health, social functioning, and scale total score of the ASD group were significantly lower than those of the three comparison groups. The school functioning score domain was lower in the ASD group than in the asthma and HC groups. In contrast, the emotional functioning domain assessments did not reveal statistically significant differences between the ASD group and the comparison groups. In the ASD group, the total problem score, inattention, and hyperactivity scores were significantly higher than both the asthma and HC groups, and the internalizing scores were higher than the healthy group. Conclusion: The poor QoL is most likely due to functional losses and problem behaviors related to ASD and may negatively affect not only children with ASD but also the whole life of the family.

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and behavioral problems. Various genetic and environmental factors, including oxidative stress, are claimed to play a role in the etiopathogenesis of ASD. In this study, we aimed to examine the status of oxidative metabolism in ASD and the association between oxidative parameters and ASD symptom severity and subtype of ASD. Method: Thirty-three children and adolescents diagnosed with ASD (16 children diagnosed with autistic disorder, 13 children with pervasive developmental disorder not otherwise specified, and 4 children with Asperger syndrome) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 28 healthy controls, aged 2-17 years, were recruited in this study. Total oxidant status (TOS) and total antioxidant status (TAS) were evaluated using Rel Assay Kit in children and adolescents. The oxidative stress index (OSI) was calculated by dividing the TOS values by the TAS values. Autistic symptoms for these patients were scored on the Childhood Autism Rating Scale (CARS). Results: In patients with ASD, TAS was statistically significantly lower and OSI statistically significantly higher than in healthy controls. There were no statistically significant differences in TOS between the ASD and control groups. There were no statistically significant differences between the subtypes of ASD in terms of oxidative stress parameters. In addition, TAS, TOS, and OSI values did not differ statistically significantly between the patients' CARS groups, and were not associated with the CARS scores of the patients. Conclusion: Our findings suggest that oxidative imbalance is present in ASD and that oxidative stress may play a role in the etiopathogenesis of ASD. Therefore, it is suggested that antioxidants may have beneficial effects on ASD and may be a new therapeutic target in treating ASD.

Objective: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene. Methods: This study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creative (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum. Results: The NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers, Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers. Conclusion: These findings suggest that polymorphisms of the COMT gene can account for individual differences in neurochemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.

Objective: Alcoholism is associated with genetic variants of genes related to alcohol metabolizing enzymes, dopaminergic, gamma-aminobutyric acidergic, glutamatergic, opioid, cholinergic, and serotonergic systems. Neurpeptide Y system and Neurexins were shown to be associated with alcohol dependence. Recent studies identified new genetic polymorphisms related to endogenous cannabinoid system, neuropetide Y and neurexin. In the present study, we aimed to investigate the association of Neurpeptide Y LEU7PRO rs16139 and neurexin 3 gene rs760288 polymorphisms with alcohol dependence in patients with alcohol dependence and healthy control subjects. Methods: 123 patients who were diagnosed with alcohol dependence according to the DSM-IV criteria and 159 healthy volunteers were included in the study. Blood samples were used to investigate polymorphisms. The genotyping of the neurexin 3 gene rs760288 and the neuropetide Y gene Leu7Pro rs16139 polymorphisms was performed using TaqMan SNP Genotyping Assays Real-Time PCR System. Results: Of the 2 genetic polymorphisms investigated in the present study, we detected association between and neurexin 3 gene rs760288 polymorphisms with alcohol dependence. Conclusions: Neurexin gene polymorphisms might be an important factor in development of alcohol addiction.

Objective: To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). Methods: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel H-1 MRS when medication naive and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. Results: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016). Conclusion: Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings.

The aim of the study was to determine the differences between expression levels of certain miRNAs, as their association with schizophrenia has been well presented in the literature, and to investigate their relation to treatment resistance in schizophrenic patients. Three groups were formed: 1) treatment-resistant group, 2) treatment responsive group and 3) healthy control group. Expression levels of miRNAs from peripheric blood samples were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We investigated the roles of 29 schizophrenia-related miRNAs in schizophrenia treatment and their potentials to be considered as indicators. Among these miRNAs, only miR-181b-5p, miR-195-5p and miR-301a-3p expressions were found to be significantly different between the treatment-resistant group and the group responding well to the treatment. miRNAs may cause resistance by silencing the receptor genes of the drugs used for schizophrenia treatment. miR-181b-5p, miR-195-5p and miR-301a-3p may be candidate indicators that can be used to reveal resistance against schizophrenia treatment.

OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene. METHODS: This study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum. RESULTS: The NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers. Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers. CONCLUSION: These findings suggest that polymorphisms of the COMT gene can account for individual differences in neurochemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.

INTRODUCTION: In this article, the COMT gene val(158)met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated. PATIENTS AND METHODS: A total of 71 children diagnosed with ADHD and 24 controls aged 8-15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA). RESULTS: First, an interaction between the COMT val(158)met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism. CONCLUSION: Significant differences reported here may be evidence that the COMT gene val(158)met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.

Introduction: In this article, the COMT gene val(158)met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated. Patients and methods: A total of 71 children diagnosed with ADHD and 24 controls aged 8-15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA). Results: First, an interaction between the COMT val(158)met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism. Conclusion: Significant differences reported here may be evidence that the COMT gene val(158)met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.

PubMed ID: 23108080, Background/Aims: Our purpose in this study was to analyze telomere length and telomerase activity before and after eradication treatment in gastric mucosa in patients positive for H. pylori. Methodology: There were two groups: a control group (n=17) and a study group (n=21). For H. pylori eradication, the patients were administrated proton pump inhibitor (PPI) + clarithromycin + amoxicillin or PPI + metronidazole + tetracycline + bismuth for 14 days. Telomere length was analyzed with RT-PCR and telomerase activity with PCR-ELISA on biopsy specimens from the antrum. The result p

PubMed ID: 24772975, The endoplasmic reticulum (ER) is related to the various signal routes that are activated in unfolded protein response (UPR). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expressions demonstrate UPR activity. In this study, we investigated the UPR gene expressions in larynx epidermoid carcinoma (HEp2) to which dexamethasone (dex) was applied. HEp2 cells were administered for 48 h with different combinations using 0.1 µM and 1 µM dex, 1 mM phenyl butyric acid (PBA) and 100 ng/ml lipopolysaccharide (LPS). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expression was determined using quantitative RT-PCR. The Grp78, MTJ1 and HMOX1 gene expression increased with the administration of 1 µM dex. CHOP expression, on the other hand, decreased with 0.1 µM dex. When dex was combined with LPS, nearly all gene expressions decreased. The increase in Grp78, Grp94, HMOX1 and MTJ1 gene expression was greater in groups in which dex was administered in combination with PBA than in groups in which dex was administered alone. Dex in low dose (0.1 µM) caused a decrease in CHOP expression in HEp2 cells and an increase in Grp78 expression, in particular. The changes in UPR genes expressions may lead to the extended survival of the cells.

Objective: The aim of this study is to reveal the relationship between internet addiction (IA) and smoking and alcohol use among university students. Method: 2096 students attending Pamukkale University were included in the study. Data collection tools were, Internet Addiction Scale (IAS), CAGE Test and Sociodemographic Data Form which was formed by the study authors for the present study to collect data about the student's age, sex, alcohol and cigarette use history and internet use characteristics (time spent online, type etc.). Results: The prevalence of internet addiction was found as 8.6% in our study group. Higher rates of smoking and alcohol use were found among students with internet addiction. In addition, students who smoke and use alcohol had significantly higher IAS scores compared to the students without alcohol or cigarette use. In our study positive relationship was found between IAS scores and CAGE scores. The frequency of alcohol use was found to increase significantly as the IAS scores increase. There was no significant difference between the groups in terms of the daily cigarette consumption amount. However, the average time spent on cigarette use was significantly higher in the group with internet addiction. In addition IAS scores were found to increase significantly as the smoking year and the amount of daily cigarette smoking increased. Discussion: According to the findings of our study, internet addiction seems to be a common problem among university students. Internet addiction was found to be associated with smoking and alcohol use.

WOS: 000341974800007 PubMed: 24943970 BACKGROUND: 1,1-dimethylbiguanide hydrochloride (biguanide metformin) is a hypoglycemic agent that is widely used in the treatment of Type 2 diabetes. Use of metformin was found to be associated with the lower risk of cancer. It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR). Although the effects of metformin treatment of various types of cancers are defined with many mechanisms, the literature provides only sufficient information about how it affects the SGK-1, Par-4 and Cav-1 mRNA expressions and the impact of this effect on cytotoxicity. The breast cancer is globally one of the most important causes of cancer-related mortality for women. We, therefore investigated the possible effects of metmorfin on proliferation, cytotoxicity and some unfolded protein response (UPR) genes in the breast cancer cells (MCF-7). MATERIALS AND METHODS: We administrated 0.31 mM, 2.5 mM and 10 mM of metformin alone and in combination with 2-DG to the MCF-7 cells and monitored the cell viability and proliferation with real-time cell analyzer system for 48 hours. We also measured CHOP, Cav-1, HO-1, SGK-1 and Par-4 genes mRNA expression levels using Real Time-Polymerase Chain Reaction (RTPCR). We considered the GAPDH gene as reference gene and the control groups as calibrator. We performed an analysis for relative gene expressions of the study groups. RESULTS: Metformin caused transcriptional regulation of UPR and tumor-related genes in MCF-7 cells and inhibited the proliferation depending on the dose, resulting in cytotoxic effect. CONCLUSIONS: We consider that administration of metformin with chemotherapeutic agents could be an effective method in treatment of breast cancer through mechanisms such as reduced resistance to chemotherapy and increased cytotoxic activity.

15th Annual European Congress of Rheumatology (EULAR) -- JUN 11-14, 2014 -- Paris, FRANCE WOS: 000346919805515 …

WOS: 000209838201124 …

Guvenc, Tolga/0000-0003-1468-3415 WOS: 000332779900011 PubMed: 24605218 Background: Lung contusion is an important factor that affects mortality and morbidity of lung injury after blunt chest trauma (BCT). The present study aims to evaluate the effectiveness of different treatment regimens on BCT-induced lung injury. Methods: A total of 35 Sprague Dawley rats were divided into five experimental groups (n = 7): sham, control; BCT; BCT + MP, BCT group treated with methylprednisolone (MP; 30 mg/kg on first day and 3 mg/kg/d on the following days); BCT + Q, BCT group treated with quercetin (Q; 50 mg/kg/d for seven days); and BCT + MP + Q, BCT group treated with the same doses of MP and Q. Serum Clara Cell Protein-16 (CC-16), thiobarbituric acid reactive substances (TBARS), and superoxide dismutase (SOD) levels were analyzed to determine histopathological changes in the lung tissues. Results: Elevated serum CC-16 and TBARS levels and reduced serum SOD levels were found in the BCT group compared to the Sham group. There was a significant change in the serum CC-16 levels in the BCT + MP group compared to the Sham group. Serum TBARS levels were significantly lower in the BCT + MP and BCT + Q group compared to the BCT group. The combined therapy regimen yielded significantly decreased CC-16 levels and increased serum SOD levels compared to the individual treatment groups. Serum TBARS levels did not significantly differ between the BCT + MP + Q group and the other treatment groups. Compared to the BCT + MP + Q group, the BCT + MP group showed significantly lower alveolar edema (AED) and alveolar exudate (AEX) scores, while the BCT + Q group showed significantly lower peribronchial inflammatory cell infiltration (PICI) and AED scores. Conclusions: The combined usage of quercetin and low dose MP treatment after initial high dose MP at the early stage of lung injury after BCT is more effective.

OBJECTIVE: Obsessive compulsive disorder (OCD) is a clinically heterogeneous disorder; OCD with poor insight has been suggested to be a specific clinical subtype. Neurological soft signs (NSSs) may be helpful to identify the specific subtypes of OCD patients. METHODS: In the present study, we aimed to compare OCD patients with poor insight with OCD patients having good insight, and healthy individuals. Sixty-four OCD patients (38 with good insight and 26 with poor insight), and 32 healthy subjects were enrolled in the present study. The Overvalued Ideas Scale (OVIS) was used to determine OCD patients with poor insight. NSSs were assessed by using the Neurological Evaluation Scale (NES). RESULTS: Two OCD groups had significantly higher total NES scores compared to controls (p=.000). Compared to healthy controls, OCD patients with poor insight performed significantly worse on all NES subscales, and they had significantly more NSSs on motor coordination, and sensory integration subscales compared to the OCD with good insight group. CONCLUSION: Our results suggested that OCD patients with poor insight exhibit more extensive neurodevelopmental impairments compared to OCD patients with good insight.

Objective: Obsessive compulsive disorder (OCD) is a clinically heterogeneous disorder; OCD with poor insight has been suggested to be a specific clinical subtype. Neurological soft signs (NSSs) may be helpful to identify the specific subtypes of OCD patients. Methods: In the present study, we aimed to compare OCD patients with poor insight with OCD patients having good insight, and healthy individuals. Sixty-four OCD patients (38 with good insight and 26 with poor insight), and 32 healthy subjects were enrolled in the present study. The Overvalued Ideas Scale (OVIS) was used to determine OCD patients with poor insight. NSSs were assessed by using the Neurological Evaluation Scale (NES). Results: Two OCD groups had significantly higher total NES scores compared to controls (p=.000). Compared to healthy controls, OCD patients with poor insight performed significantly worse on all NES subscales, and they had significantly more NSSs on motor coordination, and sensory integration subscales compared to the OCD with good insight group. Conclusion: Our results suggested that OCD patients with poor insight exhibit more extensive neurodevelopmental impairments compared to OCD patients with good insight. (C) 2011 Elsevier Inc. All rights reserved.

PubMed ID: 22757644, Ouabain is a cardiotonic steroid and specific inhibitor of the Na +/K+-ATPase. The relationship between ouabain treatment and the unfolded protein response (UPR) in cells is not precisely understood. Therefore, we studied the possible effects of ouabain on proliferation, apoptosis, and the UPR. HepG2 cells were cultured overnight and then treated with various concentrations of ouabain (0.75 to 750nM) in the absence or presence of 10mM 2-deoxyglucose (2-DG) for 48 hours. We also used real-time polymerase chain reaction to obtain quantitative measurements of expression levels of Grp78, Grp94, CHOP, MTJ-1, HKII, MDR-1, MRP-1, HO-1, and Par-4. Cell number, viability, and proliferation of HepG2 cells were monitored with a real-time cell analyzer system (xCELLigence). We show that ouabain modulates the UPR transcription program and induces cell death in glucose-deprived tumor cells. Ouabain at all concentrations showed no cytotoxicity whereas all concentrations were very effective under 2-DG stress conditions. Our findings show that disruption of the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical basis for developing UPR-targeting drugs against solid tumors. Ouabain use as an adjunct to conventional cancer therapy also warrants vigorous investigation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.