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Drug-induced acute dystonia is usually associated with combination therapies of neuroleptics, but rarely with the withdrawal or rebound effect of various psychotrops. Very sparse reports have described acute dystonia as a methylphenidate withdrawal (rebound effect), particularly in combination modalities. However, there is no case report or research regarding acute dystonia related to the withdrawal of the short-acting methylphenidate-immediate release form (MPH-IR) in the case of monotherapy of MPH-IR or a combination with guanfacine. Herein, a pediatric case of recurrent acute dystonia with two separate phenomena, locating orolingual and oromandibular/lower extremities, is presented as a withdrawal adverse reaction occurring after abrupt discontinuation of MPH-IR when under a combination therapy with guanfacine. Various options such as anticholinergic agents, re-administrating MPH, or turning to monotherapy from combination modalities, can be suggested in treatment, as well as only hydration may also have the benefit of resolving the symptoms, as in the current case. Practitioners should be aware of all possible adverse effects of MPH, even the rebound effect of short-acting forms.

It was aimed to evaluate the relationships between neuropsychological functions, self-reported metacognitive abilities, and resilience levels among children with Attention Deficit Hyperactivity Disorder (ADHD) and those with Cognitive Disengagement Syndrome (CDS) compared to healthy controls. This cross-sectional, case-control study was consisted of 36 children with CDS only, 36 with ADHD only, 33 with CDS and ADHD and 39 control children were enrolled for a total sample of 144 children. The intellectual and neuropsychological functioning of the participating children was evaluated using the WISC-IV. Metacognitive Awareness Inventory for Children(MAI-C), Emotional Resilience Scale(ERS), and Revised Child Anxiety and Depression Scale(RCADS) were used. In both Processing Speed Index (PSI) and Perceptual Reasoning Index (PRI), children with CDS had significantly lower scores compared to those with ADHD, while those with ADHD and ADHD + CDS were similar to each other and controls. Children with CDS had greater metacognitive awareness than those with ADHD only and those with ADHD + CDS, whereas controls had the greatest level of metacognitive awareness. The emotional sensitivity of children with CDS was similar to that of children with ADHD + CDS and significantly greater than that of children with ADHD and controls, while control children had the lowest levels. The results of this study suggest that metacognitive abilities and emotional resilience may be targeted in rehabilitation/therapy of children with CDS ± ADHD and that interventions targeting processing speed and perceptual reasoning in younger children with CDS symptoms may be beneficial.

This study investigates pragmatic language impairment, Theory of Mind (ToM), and emotion regulation in adolescents with Developmental Dyslexia(DD). The Social Responsiveness Scale-2(SRS) and Children's Communication Checklist-2(CCC-2) scores were found to be statistically significantly higher in the DD group than in healthy controls. DD group had lower performance in ToM skills and they have more difficulties in emotion regulation. We also found that CCC-2 and ToM scores were significantly correlated in adolescents with DD. These results may be important in understanding the difficulties experienced in social functioning and interpersonal relationships in adolescents with DD.

Objective: This study aimed to investigate social cognition and empathy properties in children among Disruptive Mood Dysregulation Disorder (DMDD) + Attention and Hyperactivity Disorder(ADHD); ADHD and healthy controls from Türkiye., Methods: Twenty-two children with DMDD were compared to matched 30 children with ADHD and 60 healthy controls. We administered Affective Reactivity Index (ARI), KaSi Empathy Scale, Kiddie-SADS, and Reading Mind in the Eyes Test (RMET) to evaluate Theory of Mind skills to all study participants., Results: DMDD + ADHD group had lower performance in ToM skills and empathy than in two groups. The ARI scores were found to be statistically significantly higher in the DMDD group than in two groups. It was also found that ARI, empathy, and ToM scores were significantly related in children with DMDD + ADHD., Conclusion: These results might be important to understand the difficulties in social functioning and interpersonal relationship in children with DMDD and ADHD. Children with DMDD may attend specific therapeutic programs which include specific techniques in social cognition, emotion regulation, and irritability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Periodical health examination is one of the important factors influencing a healthy lifestyle. Patients undergoing routine physical examination in primary care are included in the scope of preventive medical services, which is the most basic principle of primary care. Identifying the risk factors enables individuals to adopt healthier lifestyle practices. In our study, we examined the correlation between patients undergoing coronary angiography for suspected coronary stenosis and the extent of primary care services they had received in their medical history, along with the severity of stenosis observed during the angiography. Patients were interviewed using a pre-structured questionnaire to gather information about their past utilization of primary healthcare services related to coronary matters and their cardiovascular (CV) risk profile as documented in their medical history. The necessary standard tests for angiography procedures were retrieved from patient records. The SYNTAX score, a tool that aids in the objective assessment of the severity of coronary artery disease (CAD), was computed and documented. This score was then compared with the history of primary care utilization. The patients' utilization of services from the Primary Healthcare Center (PHC) was evaluated using a scoring system, with an average score of 29.27 ± 11.27 out of 100 points (minimum: 20; maximum: 60). The average SCORE Türkiye indicating the 10-year risk of CV events for all patients was calculated as 14.31% ± 8.65% (high-very high risk), while the average SYNTAX score was 15.20 ± 9.97. There was a positive and significant correlation found between fasting blood glucose and creatinine values with both SYNTAX score and SCORE Türkiye (respectively; R = 0.238, P = .013; R = 0.289, P = .002). Factors such as smoking and metabolic syndrome were associated with CAD severity. It important to highlight that individual recommended for angiography had a notably lower utilization of healthcare services from the PHC based on their medical histories. This circumstance has resulted in individuals who do not undergo CV event screenings at PHCs having higher SYNTAX scores, indicating more severe CAD that necessitates angiography. Conducting regular periodical health examinations at PHCs can help mitigate these statistics., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There may be many risk factors for both youth offending and victimization. In our study, we aimed to compare youth offenders and victims in terms of attachment characteristics, emotion regulation, and mind-reading skills., Methods: This study employed a single-center, cross-sectional, case-control design. Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version along with diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were administered by clinicians. Mind-reading skills were assessed with Reading the Mind in the Eyes task (RMET) and Faces test. Difficulties in Emotion Regulation Scale (DERS) and Inventory of Parent and Peer Attachment-Short Form (IPPA-SF) were used for assessing attachment and emotion regulation properties., Results: : When we compared the two groups in terms of IPPA-SF, DERS, RMET and Faces test, we found that victimized and offending youth did not differ significantly in terms of attachment to peers and communication/trust domains of parental attachment. Youth offenders and victims differed significantly in terms of DERS- Non-acceptance and Goals both ( P = .031 and .045; respectively). Offending youth scored significantly higher in Non-acceptance, while victimized youth scored significantly higher in Goals., Conclusion: : Offending youth were more alienated from their parents, were experiencing problems with emotional acceptance, and had lower theory of mind and emotion recognition skills compared to victimized youth. Therefore, protective interventions supporting parent-adolescent communication/attachment, as well as emotion recognition/regulation and theory of mind skills of youth, may protect children from both victimization and delinquency., Competing Interests: Declaration of Interests: The authors have no conflict of interest to declare., (2023 The authors.)

Objective: Studies have shown that theory of mind, emotion regulation and pragmatic abilities are negatively affected in people with obsessive-compulsive disorder ( OCD). We aimed to investigate theory of mind (ToM) abilities, social responsiveness, pragmatic language, and emotion regulation skills in children with OCD and to compare them to healthy controls., Methods: This study was designed as a single-center, cross-sectional, case-control study. ToM abilities were evaluated via "Reading the Mind in the Eyes Test" (RMET), "Faces Test", "Faux-Pas Test", "Comprehension Test" and "Unexpected Outcomes Test". Social responsiveness, pragmatic language and emotion regulation were evaluated by Social Responsiveness Scale (SRS), Children's Communication Checklist- Second Edition (CCC-2), Difficulties in Emotion Regulation Scale (DERS) and Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Within the study period, we enrolled 85 adolescents (42 with OCD and 43 controls)., Results: The OCD group performed significantly lower than healthy controls in the Faux Pass and Comprehension tests ( p  = 0.003 for both). We found a statistically significant difference between groups in terms of the goal, strategy, non-acceptance subscales of the DERS ( p  < 0.001, p  = 0.006, p  = 0.008, respectively) as well as the total DERS score ( p  < 0.001). CY-BOCS total scores correlated significantly and negatively with Comprehension, Faux Pas and Unexpected Outcomes tests, and positively with CCC total, SRS total and DERS total scores. In regression analysis the DERS, SRS and CCC tests emerged as significant predictors of CY-BOCS total score., Conclusion: Addressing ToM, pragmatic, and ER difficulties when planning the treatment of young people with OCD may contribute to positive outcomes.

Introduction: The aim of this study was to compare children with Specific Learning Disorders (SLD) and matched controls in terms of nonverbal communication skills, understanding of emotions, electrodermal activity (EDA) changes and response latencies measured with affective stimuli., Method: The study was designed as a single-center, cross-sectional, controlled study. KA-SI Empathic Tendency Scale-Child Form, Test of Perception of Affect-Via Nonverbal Cues (TPANC) were used for both groups. The TPANC test was performed in 4 different sessions (for picture, video, audio and textual stimuli), and during each session, the EDA was measured from the non-dominant hand. Stimuli were given at 15 second intervals in the tests and phasic changes within 3-8 seconds after the stimulus was accepted as skin conductance responses related to the stimulus in accordance with the literature. The responses and response latency during the TPANC test were recorded by the clinician., Results: 31 children with SLD and 31 healthy controls were included in the study. The mean ages for SLD and controls were 10 years 6 months and 10 years 1 month; respectively. In the SLD group, the number of correct responses in all subtests of TPANC was statistically significantly lower than controls (p<0.05). When TPANC subtests response latencies were compared, there was a significant increase in the SLD group compared to controls (p<0.05). The groups did not display a significant difference in EDA changes while providing responses in TPANC., Conclusion: Our results contribute to the literature on the affect recognition and its autonomic correlates among children with SLD. However, dependence on a single-modality for autonomic nervous system reactivity and limited sample size may affect our results and further studies with larger samples employing multiple domains of autonomic reactivity may be needed., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest., (Copyright: © 2022 Turkish Neuropsychiatric Society.)

Background: In this study, we aimed to evaluate the serum neurotensin (NT) levels and their relationships with self-reported anxiety, emotion regulation skills and impulsivity in healthy and obese adolescents., Methods: Adolescents who gained weight between 12- 17 years of age and who were above the 95th percentile (p) for body mass index (BMI) > 95p were compared with age- and gender-matched healthy adolescents with a BMI of 3-85 p. Anthropometric measurements were performed, and serum NT levels were analyzed with ELISA method in all participants. Barrat Impulsivity Scale-11 (BIS-11), Screen for Child Anxiety Related Disorders (SCARED) and Difficulties in Emotion Regulation Scale (DERS) were used for evaluating self-reported impulsivity, anxiety and emotion regulation. MANOVA with follow-up univariate ANOVAs (Bonferroni corrected) were used for group comparisons. P was set at 0.05 (two-tailed)., Results: Sixty-five obese and 65 healthy adolescents were included in the study. In the obese group, NT levels were significantly elevated compared to the control group. Self-reported emotion-regulation difficulties, anxiety and impulsivity were significantly elevated among obese adolescents. Serum NT levels among the obese group were positively correlated with emotion dysregulation and impulsivity scores., Conclusions: In this study, we found emotional dysregulation, anxiety, impulsivity, and serum NT levels were significantly elevated among obese adolescents compared to controls. NT levels in the obese group correlated with impulsivity and emotion dysregulation. Further studies should evaluate the potential role of NT in the etiology of psychopathology among adolescents who are obese.

Objective: This study aimed to investigate the effects of drug holidays during summer vacations among children with attention deficit/hyperactivity disorder (ADHD) who were treated with methylphenidate in terms of ADHD symptoms and executive functions., Methods: The study was a prospective cohort study that includes pre-treatment, post-treatment and post-drug holiday evaluations. ADHD symptom severity was evaluated with the Clinical Global Impression Scale (CGI), the Conners' Parental Rating Scale-Short Form (CPRS) and the Conners' Teacher Rating Scale- Short Form (CTRS). The Stroop Color Word Test- TBAG Form (SCWT) was used to evaluate executive functions. Fifty-one patients participated in the study according to the inclusion and exclusion criteria. Methylphenidate (MPH) was started at 0.5 mg/kg/day and titrated weekly to a maximum of 1.2 mg/kg/day. During the follow-up period, 22 (43.0%) of the patients stopped treatment., Results: Completion times for all SCWT subtests were significantly reduced after treatment ( p  < 0.001, p  = 0.002, p  < 0.001, p  = 0.002, p  < 0.001; respectively). Mean number of corrections in SCWT-3 and mean number of errors as well as corrections in SCWT-5 significantly reduced after treatment ( p  = 0.047, p  = 0.005, p  = 0.007; respectively). Mean number of corrections in SCWT-3 and mean number of errors in SCWT-5 increased significantly after drug holiday compared to post-treatment ( p  = 0.032 and p  = 0.037; respectively)., Conclusion: Our results suggest that psychomotor speed and resistance to interference improved in children with ADHD receiving methylphenidate treatment. Drug holidays did not affect psychomotor speed while beneficial effects on resistance to interference were reduced with drug holidays.

Introduction: Studies have suggested that attachment styles are associated with social anxiety disorder (SAD). Recent studies found that individuals with a diagnosis of SAD were significantly impaired relative to healthy controls on tasks of theory of mind (ToM). We aimed to investigate the association of ToM and attachment styles in adolescents diagnosed with SAD in this study., Methods: Drug-naïve 42 adolescents diagnosed with SAD and aged between 12 to 18, without psychiatric comorbidity were enrolled in the patient group. Forty-two adolescents in the same age range without any psychiatric disorders were matched as the healthy control group. The diagnosis was made by experienced clinicians using the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition. The severity of SAD symptoms was evaluated with the Social Anxiety Scale for Adolescents. ToM was evaluated with Reading the Mind in the Eyes task and faces test. Parent and Peer Attachment Inventory was used for assessing attachment properties., Results: Adolescents with SAD compared to healthy control groups have more difficulties both in Reading the Mind in the Eyes task and faces test. We found a statistically significant decrease in peer and parent attachment scores when compared with SAD and healthy controls (p<0.05). A negative correlation between the severity of SAD and both ToM tasks and attachment has been found., Conclusions: The results of this study indicate that ToM deficits and insecure attachment style may play an important role in the etiology and treatment of SAD in adolescents., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2020 Turkish Neuropsychiatric Society.)

Background: Persistent isolated elevation of aspartate aminotransferase (AST) is a rare observation and might lead to unnecessary laboratory testing and invasive procedures, if the possibility of macro-AST is not considered., Methods: We report the case of a healthy 28-year-old female patient with persistent isolated elevation of AST. In order to confirm the suspected diagnosis of macro-AST, polyethylene glycol (PEG) precipitation and repeated measurements of enzyme activity after refrigeration at 2 - 8°C were performed., Results: PEG precipitation confirmed the presence of macro-AST, while repeated measurements after refrigeration did not show any relevant decrease in enzyme activity., Conclusions: Especially in clinically asymptomatic patients, macro-AST must be considered as a cause of persistent isolated elevations in AST activity to avoid costly and potentially harmful medical tests or procedures. PEG precipitation is a feasible and cost-effective way to establish the diagnosis, while repeated measurement of enzyme activity after refrigeration potentially leads to wrong conclusions.

Diabetes is an important metabolic disease affecting many organs and systems in the body. The nervous system is one of the body systems affected by diabetes and neuropathic complications are troublesome in diabetic patients with many consequences. As diabetes has deleterious influences almost on bodily systems, an integrative approach seems to be necessary accepting the body as a whole and integrating body systems with lifestyle and living environment. Like some traditional health systems such as Ayurveda, integrative approach includes additional modalities to overcome both diabetes and diabetic complications. In general, these modalities consist of nutraceuticals and plant products. Prebiotics and probiotics are two types of nutraceuticals having active ingredients, such as antioxidants, nutrient factors, microorganisms, etc. Many plants are indicated for the cure of diabetes. All of these may be employed in the prevention and in the non-pharmacological management of mildto- moderate diabetes. Severe diabetes should require appropriate drug selection. Being complementary, prebiotics, probiotics, plants and exercise may be additive for the drug therapy of diabetes. Similarly, there are complementary approaches to prevent and cure neurological and/or behavioral manifestations of diabetes, which may be included in therapy and prevention plans. A scheme is given for the prevention and therapy of comorbid depression, which is one of the most common behavioral complications of diabetes. Within this scheme, the main criterion for the selection of modalities is the severity of diseases, so that personalized management may be developed for diabetic patients using prebiotics and probiotics in their diets, plants and drugs avoiding possible interactions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In attention deficit hyperactivity disorder (ADHD), deteriorations of brain gut axis has been shown in previous studies. One area where the most important challenges are seen in ADHD is social functioning. Zonulin is a protein found in the intestinal intraepithelial component; it has been shown that the level of zonulin increases when intestinal permeability is impaired. Changes in intestinal function were shown in ADHD. Zonulin has been shown to be associated with social impairment in children with autism spectrum disorder. In this study, it was aimed to evaluate the relationship between the ADHD symptoms and zonulin in children with ADHD. Secondarily relation of zonulin and difficulties in social functioning was examined in these children., Methods: Forty children diagnosed with ADHD and forty-one healthy children similar age and gender to ADHD group and their mothers were included in the study. Children without any chronic systemic immunological or infectious diseases were included in the case and control group. The ADHD symptoms were scored by the DuPaul ADHD scale and the social functioning of the children was assessed by the Social Responsiveness Scale (SRS). Serum zonulin levels were analyzed by enzyme-linked immunosorbent assay., Results: Children with ADHD had higher serum zonulin levels and were more impaired in social functioning compared to controls. The level of zonulin was independently predicted with hyperactivity symptoms and SRS scores in regression analysis., Conclusion: In this sample of children with ADHD, elevated zonulin levels were associated with increased symptoms of hyperactivity and impairment of social functioning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Studies have shown that children with anxiety disorders (ADs) present impaired family functioning and quality of life. We aimed to evaluate family functioning and quality of life among children with AD and healthy controls., Design and Setting: Cross-sectional study (survey) at two centers in Turkey., Methods: The study group comprised 42 children diagnosed with AD and 55 controls. The Screen for Child Anxiety-Related Emotional Disorders (SCARED) questionnaire was filled out by their parents to measure the severity of anxiety symptoms. Family functioning among the children was assessed using the Family Assessment Device (FAD) and Parental Attitude Research Instrument (PARI). The children's quality of life was assessed through the Pediatric Quality of Life Inventory (PedsQL)., Results: The children's average age was 10.00 ± 0.21 years in the AD group and 9.98 ± 1.53 years among the controls. There were higher scores on all FAD subscales in the AD group (2.15 ± 0.52; 2.29 ± 0.44; 2.44 ± 0.55; 2.10 ± 0.61; 2.56 ± 0.40; 2.32 ± 0.33; and 2.29 ± 0.47). On PARI subscales, there were significant differences favoring the AD group (p < 0.05), except for democratic attitude. All PedsQL subscales differed significantly between the groups, favoring the AD group. A statistically significant relationship was found between all PedsQL subscales and SCARED scores in the AD group., Conclusion: We found that both family functioning and quality of life among children with AD were negatively affected. However, further studies with larger sample sizes are required to reach stronger conclusions.

Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1 H -benzimidazol-2-yl)phenyl)-4-substituted-4 H -1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, 13 C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m , 5o , 5r , 5t , 5y , 5ab , and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m , 5o , 5r , 5w , 5y , 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans . Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol.

In the search for neuroactive compounds that mimic the nerve growth factor (NGF) activity for the protection against neurodegenerative diseases, the potential medicinal values of foods and plants attracts intense interest. Isofuranodiene is the major constituent of the essential oil of wild celery (Smyrnium olusatrum L., Apiaceae). The cytotoxic effects of isofuranodiene towards rat neuronal PC-12 pheochromocytoma cells were determined by MTT assay, while the cell differentiation was evaluated with xCELLigence real time cell analysis system (RTCA DP), and the neuritogenic activity was assessed by neurite outgrowth image analysis. Isofuranodiene at concentrations of 25 and 12.5 μM alone, or in combination with 50 nM NGF, showed a marked stimulation of neuritogenesis, but it was more effective at 12.5 μM with or without NGF. The present study reports the first evidence of the neuritogenic effects of isofuranodiene, which appears to be a promising neurotrophic and neuroprotective agent deserving further investigation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Inhibition of the proteasome has emerged as a clinically effective anticancer therapeutic approach in recent years. Bortezomib (Velcade®) showed extremely high potency against a wide range of cancer cell lines. Ixazomib (MLN9708-MLN2238), the second-generation proteasome inhibitor, selectivity and potency were similar to that of bortezomib, is currently being investigated in phase I studies. It shows superior antitumor activity in hematologic malignancy, especially multiple myelomas. In this study, for the first time, we evaluated and compared the antiproliferative and apoptotic effects of the novel proteasome inhibitor MLN2238 (the active form of MLN9708) with bortezomib using in vitro chronic myeloid leukemia. Cytotoxic and apoptotic effects of MLN2238 and bortezomib were determined by trypan blue dye exclusion assays, WST-1 cell proliferation assay, increased AnnexinV-PI binding capacity, changes in caspase-3 activity and loss of mitochondrial membrane potential (JC-1). Associated with proteasome pathway NFκB1 and c-myc mRNA expression levels were examined by the qRT-PCR method. We observed that cytotoxic and apoptotic effects on K562 cells were started at 5 μm of MLN2238 and 1 μm of bortezomib after 24 and 48 h. Also, MLN2238 and bortezomib downregulated NFκB1 and c-myc mRNA expression at 24 h. Our result revealed that MLN22238 and bortezomib had significant cytotoxic and apoptotic effects on K562 cells. Here, we first demonstrate in vitro data that support the development of MLN2238, by direct comparison with bortezomib on K562 cells.

Agomelatine is an antidepressant with a distinct pharmacological mechanism of action as an MT1 and MT2 receptor agonist and as a 5-HT2C receptor antagonist. We evaluated the chronic effects of agomelatine administration (40 mg/kg, 20 weeks) on the cognitive performance of rats in the Morris water maze task. We applied unbiased stereological quantification methods to estimate the total numbers of granular and pyramidal neurons located in the dorsal hippocampus. We also analyzed the dendritic spines of pyramidal neurons in the CA1 region using the Golgi-Cox impregnation method. The agomelatine-treated group found the hidden platform more quickly than did the control group and spent significantly more time in the target quadrant. Agomelatine administration caused significant volumetric and numerical enhancements in granular and pyramidal neurons in the dentate gyrus and CA1-3 subregions, respectively. Increased densities of the mushroom and stubby types of spines, with no alteration in the thin-shaped spines, were observed in the agomelatine-treated group. These results showed that long-term agomelatine administration induced a nootropic effect supported by structural changes. Enhancement of the more stable types of dendritic spines might indicate improved adaptive capacity in hippocampal neurons. Future studies will provide a better understanding of the effect of this drug on synaptic plasticity.

This study used various experimental pain methods to investigate the effects of subacute mianserin administration on diabetes-induced neuropathic pain in rats. The effect of mianserin on hyperalgesia occurring in connection with peripheral diabetic neuropathy was examined using the Randall-Selitto (mechanical nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold-plate (4°C, thermal nociceptive stimulus) tests. The dynamic plantar aesthesiometer, which measures the threshold values for mechanical stimuli, was used for allodynia studies. Thermal allodynia was evaluated with the warm-plate (38°C) test. At 30 and 45 mg/kg, mianserin effectively improved mechanical and thermal hyperalgesia occurring in connection with diabetic neuropathy. Subacute administration of mianserin also reduced diabetes-associated mechanical and thermal allodynia. The ability of mianserin to reduce diabetic neuropathic pain was comparable to that of pregabalin (10mg/kg). The antihyperalgesic and antiallodynic effects of mianserin were reversed with α-methyl-para-tyrosine methyl ester (AMPT, an inhibitor of catecholamine synthesis), phentolamine (a non-selective α-adrenoceptor antagonist), propranolol (a non-selective β-adrenoceptor antagonist), and naloxone (a non-selective opioid receptor antagonist) administrations. The same effects were not reversed, however, by para-chlorophenylalanine methyl ester (PCPA; an inhibitor of serotonin synthesis). These results suggest that the beneficial effect of mianserin on diabetic neuropathic pain is mediated through an increase in catecholamine levels in the synaptic cleft as well as through interactions with both subtypes of adrenoceptors and opioid receptors. Considering that mianserin exhibits simultaneous antidepressant and antinociceptive effects, this drug could provide a good alternative for treating the pain associated with diabetic neuropathy and the mood disorders caused directly by diabetes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Sweet cherry is an important fruit crop with increasing economical value in Turkey and the world. A number of viruses cause diseases and economical losses in sweet cherry. Prune dwarf virus (PDV), is one of the most common viruses of stone fruits including sweet cherry in the world. In this study, PDV was detected from 316 of 521 sweet cherry samples collected from 142 orchards in 10 districts of Isparta province of Turkey by double antibody sandwich-enzyme linked immunosorbent assay (DAS-ELISA). The presence of PDV in ELISA positive samples was confirmed in 37 isolates by reverse transcription- polymerase chain reaction (RT-PCR) method. A genomic region of 862 bp containing the coat protein (CP) gene of PDV was re-amplified from 21 selected isolates by RT-PCR. Amplified DNA fragments of these isolates were purified and sequenced for molecular characterization and determining genetic diversity of PDV. Sequence comparisons showed 84-99% to 81-100% sequence identity at nucleotide and amino acid level, respectively, of the CP genes of PDV isolates from Isparta and other parts of the world. Phylogenetic analyses of the CP genes of PDV isolates from different geographical origins and diverse hosts revealed that PDV isolates formed different phylogenetic groups. While isolates were not grouped solely based on their geographical origins or hosts, some association between phylogenetic groups and geographical origins or hosts were observed.

The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles.

This present study was undertaken to examine treating effects of St. John's Wort (SJW) extract on nociceptive perception of STZ-diabetic animals based on its potential antidiabetic and antinociceptive activities. One week administrations of SJW extract (125 and 250 mg/kg) induced significant decrease in high blood glucose levels of three weeks STZ-diabetic rats and improved their dysregulated metabolic parameters. In addition, SJW extract treatment caused restoration in the mechanical hyperalgesia of diabetic animals. These findings provide a rationale for the traditional use of SJW against diabetes and display the potential of this plant as a new drug candidate/source for the treatment of diabetic pain., (Copyright © 2011 Elsevier B.V. All rights reserved.)