Anxiety Disorders and Phobias: A Cognitive Perspective

Hereditary motor and sensory neuropathies, to which Charcot-Marie-Tooth (CMT) disease belongs, are a common cause of disability in adulthood. Growing awareness that axonal loss, rather than demyelination per se, is responsible for the neurological deficit in demyelinating CMT disease has focused research on the mechanisms of early development, cell differentiation, and cell-cell interactions in the peripheral nervous system. Autosomal recessive peripheral neuropathies are relatively rare but are clinically more severe than autosomal dominant forms of CMT, and understanding their molecular basis may provide a new perspective on these mechanisms. Here we report the identification of the gene responsible for hereditary motor and sensory neuropathy-Lom (HMSNL). HMSNL shows features of Schwann-cell dysfunction and a concomitant early axonal involvement, suggesting that impaired axon-glia interactions play a major role in its pathogenesis. The gene was previously mapped to 8q24.3, where conserved disease haplotypes suggested genetic homogeneity and a single founder mutation. We have reduced the HMSNL interval to 200 kb and have characterized it by means of large-scale genomic sequencing. Sequence analysis of two genes located in the critical region identified the founder HMSNL mutation: a premature-termination codon at position 148 of the N-myc downstream-regulated gene 1 (NDRG1). NDRG1 is ubiquitously expressed and has been proposed to play a role in growth arrest and cell differentiation, possibly as a signaling protein shuttling between the cytoplasm and the nucleus. We have studied expression in peripheral nerve and have detected particularly high levels in the Schwann cell. Taken together, these findings point to NDRG1 having a role in the peripheral nervous system, possibly in the Schwann-cell signaling necessary for axonal survival.

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N-MYC Downstream-Regulated Gene 1 Is Mutated In Hereditary Motor And Sensory Neuropathy-LOM

Oxidative stress is considered to be the main cause of diabetic complications. As the role of antioxidants in diabetes therapy is still underestimated, the aim of the present investigation was to study the antioxidative action of melatonin in comparison with N-acetylcysteine (NAC) under diabetic conditions. Alloxan-diabetic rabbits were treated daily with either melatonin (1 mg/kg, i.p.), NAC (10 mg/kg, i.p.) or saline. Blood glutathione redox state and serum hydroxyl free radicals (HFR), creatinine and urea levels were monitored. After 3 wk of treatment animals were killed and HFR content, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio as well as the activities of glutathione reductase, glutathione peroxidase and gamma-glutamylcysteine synthetase were estimated in both liver and kidney cortex. Diabetes evoked a several-fold increase in HFR levels accompanied by a significant decline in GSH/GSSG ratio in serum and the examined organs. In contrast to NAC, melatonin (at 1/10 the dose of NAC) attenuated diabetes-induced alterations in glutathione redox state and HFR levels, normalized creatinine concentration and diminished urea content in serum. Moreover, the indole resulted in an increase in glutathione reductase activity in both studied organs and in a rise in glutathione peroxidase and gamma-glutamylcysteine synthetase activities in the liver. In contrast to NAC, melatonin seems to be beneficial for diabetes therapy because of its potent antioxidative and nephroprotective action. The indole-induced increase in the activities of the enzymes of glutathione metabolism might be of importance for antioxidative action of melatonin under diabetic conditions.

Melatonin attenuates diabetes-induced oxidative stress in rabbits.

The European Commission asked EFSA to update their 2006 opinion on ochratoxin A (OTA) in food. OTA is produced by fungi of the genus Aspergillus and Penicillium and found as a contaminant in various foods. OTA causes kidney toxicity in different animal species and kidney tumours in rodents. OTA is genotoxic both in vitro and in vivo; however, the mechanisms of genotoxicity are unclear. Direct and indirect genotoxic and non-genotoxic modes of action might each contribute to tumour formation. Since recent studies have raised uncertainty regarding the mode of action for kidney carcinogenicity, it is inappropriate to establish a health-based guidance value (HBGV) and a margin of exposure (MOE) approach was applied. For the characterisation of non-neoplastic effects, a BMDL10 of 4.73 μg/kg body weight (bw) per day was calculated from kidney lesions observed in pigs. For characterisation of neoplastic effects, a BMDL10 of 14.5 μg/kg bw per day was calculated from kidney tumours seen in rats. The estimation of chronic dietary exposure resulted in mean and 95th percentile levels ranging from 0.6 to 17.8 and from 2.4 to 51.7 ng/kg bw per day, respectively. Median OTA exposures in breastfed infants ranged from 1.7 to 2.6 ng/kg bw per day, 95th percentile exposures from 5.6 to 8.5 ng/kg bw per day in average/high breast milk consuming infants, respectively. Comparison of exposures with the BMDL10 based on the non-neoplastic endpoint resulted in MOEs of more than 200 in most consumer groups, indicating a low health concern with the exception of MOEs for high consumers in the younger age groups, indicating a possible health concern. When compared with the BMDL10 based on the neoplastic endpoint, MOEs were lower than 10,000 for almost all exposure scenarios, including breastfed infants. This would indicate a possible health concern if genotoxicity is direct. Uncertainty in this assessment is high and risk may be overestimated.

Risk assessment of ochratoxin A in food

Expression cloning of an activin receptor, a predicted transmembrane serine kinase

Epidemiological studies indicate that ochratoxin A (OTA) may be involved in the pathogenesis of different forms of human nephropathies. Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by OTA administration in rats was investigated. Three groups of eight rats each were used: control, OTA (289 micro g kg(-1) day(-1)) and OTA + MEL (OTA, 289 micro g kg(-1) day(-1); MEL, 10 mg kg(-1) day(-1)), with treatment at two different time periods during the same day. After 4 weeks of treatment, the levels of lipid peroxidation (LPO) and the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured in homogenates of kidney. In OTA-treated rats, the levels of LPO and the activities of GSHPx and SOD were significantly decreased compared with controls. In OTA + MEL-treated rats, SOD, GSHPx and catalase activities and LPO levels were not changed significantly in comparison with controls.

Effects of ochratoxin a on oxidative damage in rat kidney: protective role of melatonin.

Various studies indicate that the mycotoxin ochratoxin A (OTA) is a carcinogenic, genotoxic, teratogenic, immunotoxic, and nephrotoxic agent. In the present study, the activities of some enzymes in the serum and liver of rats with ochratoxicosis and the effects of melatonin on these enzymes were investigated. Rats were divided into three equal groups, each consisting of eight rats; control, OTA (289 μg/kg per day) and OTA + melatonin groups for this study. In the OTA treated group, the level of lipid peroxidation (LPO) and the activities of glutathione peroxidase (GSH-Px) were increased in the liver and serum in comparison with the control group. The activities of catalase (CAT) and superoxide dismutase (SOD) were significantly changed in the serum when compared with controls. Our results showed structural tissue damage in the liver in OTA-treated rats. Melatonin decreased the OTA-induced damage to support the antioxidant defense system and/or with free radical scavenger action.

The effects of ochratoxin A on lipid peroxidation and antioxidant enzymes: a protective role of melatonin

Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause Charcot–Marie–Tooth type 2 (CMT2), a severe autosomal recessive form of neuropathy associated with axonal phenotypes It has been screened in this study for the presence of mutations in the coding region of GDAP1, which maps to chromosome 8q21, in a family with CMT2 To date, 29 mutations in the GDAP1 have been reported in patients of different ethnic origins Here, we report a novel missense mutation (c836A>G), and two polymorphisms: a silent variant (c102G>C), and a 5′-splice site mutation (IVS5+24C>T) in GDPA1 gene identified in a five generation Turkish family with autosomal recessive CMT2

Novel GDAP1 mutation in a Turkish family with CMT2K (CMT2K with novel GDAP1 mutation).

Background: Considerable evidence suggests that variation of the serotonin-transporter-linked promoter region (5- HTTLPR) is associated with anxiety-related traits. Academic outcomes are also more closely related to trait anxiety. This preliminary study aimed to explore the association between academic performance and levels of anxiety with respect to the bi- and triallelic classification of 5-HTTLPR polymorphism of the 5-HTT gene in teacher candidates. Methods: In our study, Spielberger’s State-Trait Anxiety Inventory, the Selection Examination for Professional Posts in Public Organizations (KPSS) and 5-HTTLPR genotypes were used to investigate a group of 94 healthy teacher candidates. Results: Higher anxiety scores were significantly associated with the S′S′ genotype. There was no direct, statistically significant association between academic performance and genotypic groups regarding bi- and triallelic classification. However, the students who have L′L′ or LL genotypes had the lowest levels of trait anxiety and the poorest academic performance. Additionally, there was a significant positive correlation between academic performance and anxiety levels. Discussion: These findings support the idea that S and LG alleles are associated with anxiety-related traits, and that the S′S′ genotype may be a good indicator for anxiety-related traits in a sample from the Turkish population. A specific degree of anxiety is considered to be a motivation for learning and high academic performance. However, 5-HTTLPR polymorphism of the 5-HTT gene may be one of the genetic factors affecting academic performance in connection with anxiety levels. Implications for incorporating anxiety management training in the educational process in terms of both environmental and individual factors will have a very important role in improving effective strategies for student personality services, as well as for development and planning.

Serotonin Transporter Bi- and Triallelic Genotypes and Their Relationship with Anxiety and Academic Performance: A Preliminary Study

Objectives Basic Life Support (BLS) is the application of cardiopulmonary resuscitation (CPR) in order to save the lives of cardiac arrest victims by members of the public pending the arrival of the Emergency Medical Service (EMS). The aim of this study was to evaluate the effectiveness of training in order to ensure society understands the importance of early initiation of BLS, and to provide information concerning BLS and automated external defibrillators (AED). Methods This study consisted of 150 participants, of whom none were healthcare professionals. The research data were collected from 150 pre-tests and 100 post-tests. A Comparison of nominal data was analyzed by both McNemar's test and Pearson's chi-square exact test. Results Of the participants, 39% had received the BLS training prior to the study. It was observed that the participants’ desire for applying BLS increased from 43% to 78% post training, and the ratio of ability to distinguish the need for BLS increased from 54% to 79%. Our results also indicated that the knowledge level of the CPR application increased after the study. The proportion of participants who knew the purpose of using AED increased from 79.8% to 95.7%. Conclusions It was concluded that the BLS Awareness training increased in relation to the application of BLS, improved the BLS knowledge and increased awareness of the use of AED.

Mustafa Soyöz

Papers

Effects of ochratoxin a on oxidative damage in rat kidney: protective role of melatonin.

The effects of ochratoxin A on lipid peroxidation and antioxidant enzymes: a protective role of melatonin

Novel GDAP1 mutation in a Turkish family with CMT2K (CMT2K with novel GDAP1 mutation).

Serotonin Transporter Bi- and Triallelic Genotypes and Their Relationship with Anxiety and Academic Performance: A Preliminary Study

The evaluation of laypersons awareness of basic life support at the university in Izmir.