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Posttraumatic stress disorder (PTSD) is a stress-related mental disorder and develops after exposure to life-threatening traumatic experiences. The risk factors of PTSD included genetic factors; alterations in hypothalamic–pituitary–adrenal (HPA) axis; neurotrophic, serotonergic, dopaminergic, and catecholaminergic systems; and a variety of environmental factors, such as war, accident, natural disaster, pandemic, physical, or sexual abuse, that cause stress or trauma in individuals. To be able to understand the molecular background of PTSD, rodent animal models are widely used by researchers. When looking for a solution for PTSD, it is important to consider preexisting genetic risk factors and physiological, molecular, and biochemical processes caused by trauma that may cause susceptibility to this disorder. In studies, it is reported that epigenetic mechanisms play important roles in the biological response affected by environmental factors, as well as the task of programming cell identity. In this article, we provided an overview of the role of epigenetic modifications in understanding the biology of PTSD. We also summarized the data from animal studies and their importance during the investigation of PTSD. This study shed light on the epigenetic background of stress and PTSD.

Objective: The aim of the study was to evaluate the possible protective effects of alpha-lipoic acid (α-LA), donepezil and memantine combined therapy in the scopolamine-induced amnesia rat model. Objective: The aim of the study was to evaluate the possible protective effect of donepezil, memantine and alpha-lipoic acid (α-LA) combined therapy in the scopolamine-induced amnesia rat model. Methods: In this study, the effect of combined therapy used in the treatment of scopolamine-induced amnesia on behavioural parameters was evaluated using Y-maze and new object recognition (NOR) test. In addition, muscarinic acetylcholine receptor subtype M1, N-methyl-D-aspartate receptor NR2B subunit, brain-derived neurotrophic factor (BDNF) and mitochondrial apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) / Bcl-2 associated X (Bax) ratio, caspase (casp) -3, and -9] expression levels were evaluated using the western blot method in the frontal cortex and hippocampus regions. Results: The main findings of this study demonstrated that in scopolamine-induced amnesia rats, cognitive dysfunction determined by both the Y-maze and the NOR test were reversed with the combined treatment of memantine, donepezil and α-LA. According to immunoblotting results in both brain regions, scopolamine-induced decreased M1, BDNF, Bcl-2 / Bax ratio and increased NR2B, casp-3 and -9 expression levels were found to be reversed to almost control values with combined treatment. Conclusion: Consistent with the literature, our study results suggest that the positive contribution of α-LA to the combined treatment of donepezil and memantine, which is used in the routine treatment of neurodegenerative diseases, may be a treatment option in the future. Results: The main findings of this study demonstrated that in scopolamine-induced amnesia rats, cognitive dysfunction determined by both the Y-maze and the NORT test were reversed with the combined treatment of memantine, donepezil and α-LA. In addition, decreased BDNF, M1, bcl-2/bax ratio and increased NR2B, caspase-3 and caspase-9 expression levels due to scopolamine in both regions were improved with α-LA, donepezil and memantine combined therapy. Conclusion: The results of our study and other study results in the literature suggest that α-LA may be a future treatment option due to its positive contribution to the effects of other drugs used in the routine treatment of neurodegenerative diseases.

Despite many years of research, radical treatment of Alzheimer's disease (AD) has still not been found. Amyloid-β (Aβ) peptide is known to play an important role in the pathogenesis of this disease. AD is characterized by three main changes occurring in the central nervous system: (1) Aβ plaque accumulation that prevents synaptic communication, (2) the accumulation of hyperphosphorylated tau proteins that inhibit the transport of molecules inside neurons, and (3) neuronal cell loss of the limbic system. Mechanisms leading to Aβ accumulation in AD are excessive Aβ production as a result of mutations in amyloid precursor protein or genes, and impairment of clearance of Aβ due to changes in Aβ aggregation properties and/or Aβ removal processes. Human ATP-binding cassette (ABC) transporters are expressed in astrocyte, microglia, neuron, brain capillary endothelial cell, choroid plexus, choroid plexus epithelial cell, and ventricular ependymal cell. ABC transporters have essential detoxification and neuroprotective roles in the brain. The expression and functional changes in ABC transporters contribute to the accumulation of Aβ peptide. In conclusion, the review was aimed to summarize and highlight accumulated evidence in the literature focusing on the changing functions of human ABC transporter members, in AD pathogenesis and progression.

BACKGROUND/AIMS The aim of this study was to investigate the effects of Nigella sativa (NS) oil form on reducing the damage caused by indomethacin in the stomach and duodenum of rats owing to their antioxidant and anti-inflammatory properties. MATERIAL and METHODS The rats were divided into 4 groups: group 1, saline-treated control group; group 2, NS-treated control group; group 3, saline-treated ulcer group and ulcers caused by indomethacin (30 mg/kg) and administration of physiological serum; group 4, NS-treated ulcer group, which is the group receiving NS oil after administration of indomethacin. At the end of the study, blood samples collected from animals were examined for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and glutathione (GSH), malondialdehyde (MDA) levels and myeloperoxidase (MPO),and Na+/K+-ATPase activities in gastric and intestinal tissue samples. RESULTS Levels of TNF-alpha and IL-1 beta in serum and MDA and MPO values in tissue were found to be higher in the saline-treated ulcer group than in the saline-treated control group. In addition, tissue GSH and Na+/K+-ATPase levels were found to be lower. These values were found to be reversed when comparing NS-treated ulcer group to saline-treated ulcer group. Histopathological findings showed epithelial regeneration and improvement instead of dense tissue damage. CONCLUSION The strong antioxidant and anti-inflammatory effects of NS against potential small intestine and gastric damage were shown using an experimental indomethacin-induced ulcer model in rats. Hence, our study suggests that NS used together with indomethacin can prevent gastrointestinal damage; thus, this agent can create a new clinical therapeutic principle.

Methotrexate (MTX) is an effective cytotoxic agent which is used to treat malignancies and inflammatory diseases. Origanum onites (O. onites) is found throughout the Eastern Mediterranean region and has been used in traditional medicine. The essential oils (EOs) of O. onites rich in highly bioactive phytochemicals such as carvacrol (CVR) and has antiviral, antioxidant, anticancer and proapoptotic properties. The aim of this study was to investigate the protective effects of CVR and O. onites-EO treatment in MTX-induced hepatorenal toxic rats' liver and kidney tissues. The bcl-2/bax ratio, glutathione (GSH) level, malondialdehyde (MDA) level, and myeloperoxidase (MPO) activity of liver and kidney tissues were evaluated in the MTX-induced rat model. Results showed that the administration of CVR or O. onites-EO significantly increased bcl-2/bax expression and GSH levels as well as reduced MDA level and MPO activity in the kidney and liver tissues of MTX-induced rat model. In conclusion, our results suggest that O. onites-EO and CVR have protective effect in MTX-induced hepatorenal toxic rats' liver and kidney tissues by decreasing oxidative stress and apoptosis.

Objective The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model. Methods Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods. Results In the ISO group, Na+/K+ ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na+/K+ ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment. Conclusion RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium.

Objective: COVID-19 was first discovered in Wuhan in December 2019 and spread all over the world. This study was conducted to evaluate the knowledge, attitudes and behaviours of people living in Northern Cyprus regarding COVID-19.Methods: This descriptive study designed to evaluate the level of knowledge, attitude and behaviour of participants who are Turkish Cypriots between 7-17 April 2020 after the first COVID-19 case diagnosed in our country. A twenty-nine-item questionnaire was prepared, distributed randomly to participants on social media and took 7-10 min to complete. Data were analyzed with a 95% confidence and p

© 2022Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates the behavioral and neurochemical effects of JP-1302, a selective α2C-adrenoceptor antagonist, in a model of schizophrenia-like deficits induced by sub-chronic ketamine (KET) administration. Here, we administered ketamine (25 mg/kg, i.p.) to male and female Wistar rats for eight consecutive days. On the last two days of ketamine administration, rats were pretreated with either JP-1302 (1-3-10 μmol/kg, i.p.), chlorpromazine (0.1 mg/kg, i.p.), or saline, and the behavioral tests were performed. Behaviors related to positive (locomotor activity), negative (social interaction), and cognitive (novel object recognition) symptoms of schizophrenia were assessed. Glutamate, glutamine, GABA levels, and α2C-adrenoceptor expression were measured in the frontal cortex and the hippocampus. Tyrosine hydroxylase immunocytochemical reactivity was also shown in the midbrain regions. Sub-chronic ketamine administration increased locomotor activity and produced robust social interaction and object recognition deficits, and JP-1302 significantly ameliorated ketamine-induced cognitive deficits. Ketamine induced a hyperdopaminergic activity in the striatum, which was reversed by the treatment with JP-1302. Also, the α2C-adrenoceptor expression was higher in the frontal cortex and hippocampus in the ketamine-treated rats. Our findings confirm that α2C-adrenoceptor antagonism may be a potential drug target for treating cognitive disorders related to schizophrenia.

BACKGROUND/AIMS Humic acid (HA) formed by the decomposition of organic matter is a high-molecular-weight polymer. Humic-derived substances are potential drugs for human health, and their role in the prevention and treatment of diseases, like diabetes, antiviral, UV-B protective effect, cancer, and cardiovascular disease, is emphasized in various studies. It has antiulcerogenic, antitumor. Yang et al. demonstrated that HA exerts an antiproliferative effect and growth inhibition on HL-60 cells through the induction of apoptosis. A study showed that the antiulcer effect of Shilajit (HAs extracted from Shilajit) samples may be due to antimicrobial, anti-inflammatory, antianxiety, antioxidant, healing, and regenerative effects. The present study aimed to investigate the effects of HA on cultures of the chronic myeloid leukemia cell line in vitro. MATERIAL and METHODS We determined the apoptotic effect of HA in K562 cells by using various molecular methods. For cell viability, HA was tested in vitro against K562 cell lines using the MTT colorimetric process. Bax, bcl-2, casp-3, and casp-9 expressions were quantified by Western blot. Apoptosis analysis has been made with the Annexin-V/PI method. RESULTS The IC50 values of HA were determined 100 mg mL(-1) for the K562 cell line. HA has been shown to inhibit cell proliferation. As the bcl-2/bax ratio decreased and increasing the levels of caspase-3 and caspase-9, the cells underwent apoptosis. CONCLUSION As a result, HA showed the anticancer effect on leukemia cells. In the future, HA can be used as a chemopreventive agent in leukemia treatments.

OBJECTIVES: Many clinical reports describe the beneficial effects of low-dose atypical antipsychotic added to the antidepressants in the management of anxiety disorders. The aim of this study was to evaluate the effect of low-dose atypical antipsychotic when added to antidepressant treatment on cholinergic M1 receptor expression in the hippocampus and amygdale region in learning and cognitive disorders caused by anxiety. METHODS: The treatments were administered by using different test models on memory, learning, and anxiety, as well as the effect on muscarinic M1 receptor expression levels were assessed. Citalopram (10 mg/kg/sc) and combination [citalopram and risperidone (1 mg/kg/sc)] treatments were applied after stress induction using the immobilization model in rats. Animals groups were randomly divided as: control, stress, stress + citalopram, and stress + combination treatment group. Rats in stress groups were immobilized in cages for 4 h a day for 15 days. On days 1–5, groups were subjected to Morris water maze (MWM), open field, and elevated plus maze (EPM) tests. RESULTS: MWM test results have shown that citalopram induces an anxiolytic effect. Low-dose risperidone treatment has increased the antidepressant-like activity of citalopram in all tests. In OFT the number of squares that rats were circulating on the plane was increased and the time spent by the rats on the maze platform was also increased in MWM. In addition to this, the time spent by the rats on the open arms of the EPM test were also increased. Since the combined treatment increased the discovery of the environment and the active behaviour in tests; all those reflected the increase in general activity. Findings also suggest that treatments may play an effective role in altering the expression level of M1 receptors which are effective in learning and recalling information in the amygdale and the hippocampus. Combination treatment has been shown to provide a meaningful correction of stress-induced memory and learning functions. CONCLUSIONS: These findings indicate that combination treatment may help reduce the stress-induced impairments in cognitive functions.

Alzheimer's disease is a progressive neurodegenerative disorder causing common health problem with increasing age. Evidences show that the key symptoms of AD are mainly caused by cholinergic system dysfunction which has a role in cognitive disorders. Cholinergic pathways especially muscarinic receptors like M1 subtype also have a major role in learning, memory, cognitive functions and emotional state. There is no available permanent treatment currently to cure AD or to change its progression. This study was designed to investigate the factors that play important role in pathogenesis of AD and to compare the effects of Galantamine treatment with effects of Myrtus communis treatment. The expression level of M1, ACh, BDNF; AChE activity, GSH level, MDA and MPO activity and AChE gene expression were investigated in scopolamine-induced rat model. Results showed that, administration of MC significantly improves the SCOP-induced reduction of latency and object recognition time; increasing BDNF, M1 and ACh receptor expression levels in the different brain regions. Additionally, MC showed an increased in AChE by enhancing GSH activity and reducing MDA level and MPO activity. In conclusion MC considered as a possible novel therapeutic approach that can be a valuable alternative way in the prevention and treatment of AD.

Objectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1 beta levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Hepatitis E virus (HEV) is transmitted by a fecal oral route from animals to humans following exposure to the body fluids of infected animals. We investigated the seroprevalence of anti-hepatitis E (anti-HEV) antibodies by monitoring IgG and IgM virus antibodies amongst employees in the animal industry in North Cyprus through a cross-sectional study. Samples were taken from individuals without occupational exposure to animals and from those who worked with animals (doing animal husbandry, veterinary work or butchery). Enzyme-linked immunoassays were used to detect anti-HEV IgG and IgM in the blood samples. The prevalence of anti-HEV IgG antibodies was 3.0% (12/400), while the prevalence of anti-HEV IgM antibodies was 0.25% (1/400). The prevalence of anti-HEV IgG amongst the samples received from females was approximately 2.5-fold higher than samples received from males (2.4%). Anti-HEV IgG was detected amongst 7% of animal husbandry workers and amongst 2% of veterinarians and butchers. The current findings represent the first records of HEV surveillance in Cyprus. We investigated the seroprevalence of anti-HEV by monitoring IgG and IgM virus antibodies amongst employees. Hepatitis E virus (HEV) is transmitted by a fecal oral route from animals to humans following exposure to the body fluids of infected animals. We investigated the seroprevalence of anti-hepatitis E (anti-HEV) antibodies by monitoring IgG and IgM virus antibodies amongst employees in the animal industry in North Cyprus through a cross-sectional study. Samples were taken from individuals without occupational exposure to animals and from those who worked with animals (doing animal husbandry, veterinary work or butchery). Enzyme-linked immunoassays were used to detect anti-HEV IgG and IgM in the blood samples. The prevalence of anti-HEV IgG antibodies was 3.0% (12/400), while the prevalence of anti-HEV IgM antibodies was 0.25% (1/400). The prevalence of anti-HEV IgG amongst the samples received from females was approximately 2.5-fold higher than samples received from males (2.4%). Anti-HEV IgG was detected amongst 7% of animal husbandry workers and amongst 2% of veterinarians and butchers. The current findings represent the first records of HEV surveillance in Cyprus. We investigated the seroprevalence of anti-HEV by monitoring IgG and IgM virus antibodies amongst employees.

Activation of pro-inflamatuar pathways play major role in formation of major complications as a result of burns. This study was planned to investigate the protective effect of Silk Fibroin in lung injury caused by burn in the experimental rat model. After rinsing the skin of rats under ether anesthesia, the exposed back region, covers 30% of the total body, was kept in the 90°C water bath for 10s. The control rats were kept in the 25°C water bath for 10s. Immediately after burning process, silk fibroin was administered orally at a dose of 600mg/kg. After 24h following burning from all groups the levels of TNF-α, IL-1β in blood samples and the MDA, GSH and the activity of MPO were determined from taken lung tissues. Moreover, the expression of Bcl-2/Bax, Caspase-3 and Caspase-9 were determined. Significant increase in TNF-α, IL-1β, Casp-3 and Casp-9 levels were observed in the Silk Fibroin-treated burn group (p

Objective: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1 beta) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+- ATPase enzyme activities were analyzed to study tissue injury under light microscope. Results: While IR increased AST, ALT, TNF-alpha, and IL-1 beta levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values. Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

Breast cancer is the most common cancer among women and in order to create alternative treatments different types of in vivo and in vitro studies have used various plant-based therapeutic agents. Humic acid (HA) induces apoptosis and has various pharmacological properties including anti-inflammatory and anti-proliferative effects. In our study, we examined the cytotoxic effects of HA at concentrations of 5, 10, 20, 50 and 100 μg/mL in human breast adenocarcinoma MCF-7 cell line for 24 and 48 h. By using MTT method, it has been found out that HA 100 g/mL had cytotoxic effect on human breast adenocarcinoma MCF-7 cell line at both 24 and 48 h; also found out that the effective dose of HA at the same time (24 and 48 h) was 50 μg/mL. The results of our study will shed light on the development of alternative therapeutic approaches in the treatment of cancer by evaluating the cytotoxic effect of HA.

Introduction: Brucellosis causes a necrotic and inflammatory infection in humans and animals, and is among the world's most common zoonotic diseases. The aim of this study was to determine the seroprevalence of Brucella antibodies and compare serological methods in Turkish Republic of North Cyprus, where animal husbandry is common. Materials and Methods: The study was conducted between December 2017 and February 2018 and included veterinarians (n=50), animal caregivers (n=109), butchers (n=65), and a control group of individuals who had no connection with animals (n=100). Serum samples from the participants were analyzed with serological techniques including Rose Bengal test (RBT), standard tube agglutination test (STA) and ELISA; IgG and IgM methods. The sensitivity and specificity of the methods used were estimated by considering ELISA (IgG and/or IgM) results as reference/golden standard. Results: Of 27 patients (8.3%) patients who had positive results from at least one of the serological tests, 21 (6.5%) had positive RBT, 15 (4.6%) had positive STA and 10 (3.1%) had positive ELISA (IgG and/or IgM). Six (28%) patients with negative RBT results were found to be positive in ELISA. Seventeen samples (80.9%) were RBT-positive but ELISA- negative. Conclusion: These data suggest that Brucella infection is at low rate in the Turkish Republic of North Cyprus. Laboratory diagnosis should be supported by tests such as seroconversion for low titers on STA, or tests such as ELISA. Only two cases were reported to the Ministry of Health Statistics Unit in 2013.

Aim of the work To detect the frequency of hepatitis C virus (HCV) infection among patients admitted to a rheumatology ward in northern Cyprus. Patients and methods 154 patients admitted to the rheumatology department of Near East University Hospital. The demographic data, examination findings and the medical cause of admission together with clinical manifestations of their disease was recorded. All patients were screened for HCV antibodies and cryoglobulins. Results The mean age of the patients was 46.6±15.8 years. The diagnosis amongst the 154 patients included rheumatoid arthritis in 24 (15.6%), arthralgia in 15 (9.7%), ankylosing spondylitis in 12 (7.8%), fibromyalgia syndrome in 11 (7.1%), osteoarthritis in 10 (6.5%), palindromic rheumatism in 10 (6.5%), systemic lupus erythematosus in 7 (4.5%), sjogren’s syndrome in 7 (4.5%),psoriatic arthritis in 17 (11.0%), vasculitis in 5 (3.2%), raynaud phenomenon in 5 (3.2%), scleroderma in 4 (2.6%), enteropathic arthritis in 4 (2.6%), familial mediterranean fever in 4 (2.6%), gout diseases in 3 (1.9%), reactive arthritis in 7 (4.5%), behcet’s disease in 1 (0.6%) and retroperitoneal fibrosis in 1 (0.6%) patients. HCV antibodies were negative in all the patients and only 1 male tested positive for cryoglobulins. Almost a quarter of the patients were receiving non-steroidal ant-inflammatory drugs (NSAIDs) and 7.1% received colchicine. Conclusions Although rheumatic diseases are noted at a high rate in north Cyprus, there is no associated HCV infection.

Objective: The B-cell lymphoma/leukemia-2 (Bcl-2) family of proteins governs mitochondrial membrane permeability where the programmed apoptotic process is controlled by the balance between proapoptotic (Bax) and antiapoptotic (Bcl-2) proteins. We aimed to investigate the [Bcl-2]/[Bax] in different brain regions in a post-traumatic stress disorder rat model. Methods: Female Sprague-Dawley rats were exposed to dirty cat litter (trauma) for 10 min and the protocol was repeated 1 week later with a trauma reminder (clean litter) in reversed 12 h light/dark cycle. The rats received intraperitoneal saline, fluoxetine (2.5 mg/kg/day) or propranolol (10 mg/kg/day) for 7 days between exposure sessions. Following exposure to the trauma reminder, elevated plus maze experiments were done. Immunoblotting was used to quantify [Bcl-2] and [Bax] proteins in the homogenates of the dorsal hippocampus, the frontal cortex and the amygdaloid complex. Results: Fluoxetine reversed the increases in the anxiety indices and the freezing times. In the amygdaloid complex and the frontal cortex, the [Bcl-2]/[Bax] decreased in the traumatized control rats significantly (p

Objectives: Post-traumatic stress disorder (PTSD) is characterizedby life threatening trauma, overexcitation, flashbacks andnightmares. Research on PTSD is faced with the challenge ofunderstanding how a traumatic experience leads to long lastingdetrimental effects on behavior and functions of the brain. Manypharmacological agents are available in the pharmacotherapyof the PTSD where there is no adequate evidence to support theefficacy of any specific agent. It is hypothesized that M1 muscarinicreceptor subtypes might play important role in the recall ofnegative experience. The aim of this research is to investigate boththe behavioral and the molecular efficacy of chronic fluoxetine(FLU) (2.5mg/day; i.p) treatment in PTSD and also the probableeffect of pharmacotherapy on M1 muscarinic receptor subtypeexpression in rats.Materials and Methods: For experimental design randomselection was performed to all groups; Control, Stress andTreatment groups. The effects of chronic FLU treatment wereevaluated in terms of expression levels of the M1 receptors in thehippocampus and the frontal cortex of the rats’ brain.Results: When the rats were subjected to the trauma reminderon the last day of the experiment (Day 30), the anxiety indexesof the stress group were found to be significantly higher than thecontrol (P< 0.001). Moreover, it has been observed that chronicFLU treatment restored the anxiety scores in stress groups bylowering the anxiety indexes (P< 0.001).Conclusion: In this study, it has been indicated that stressinduces anxiety like behavior and reduces M1 expression in thehippocampus and the frontal cortex of the rats’ brain. These effectscan be prevented by lowering the dose of chronic FLU therapy., Amaç: Travma sonrası stres bozukluğu (TSSB) yaşamı tehdit edentravma, aşırı uyarılma, flashbackler ve kabuslar ile karakterizedir.TSSB araştırmaları, travmatik bir deneyimin beyinin davranışve işlevleri üzerinde uzun süreli bozulma etkilerine yol açtığınıanlamanın zorluğuyla karşı karşıyadır. Herhangi bir spesifik ajanınetkinliğini destekleyecek uygun kanıt olmadığında, TSSB’ninfarmakoterapisinde birçok farmakolojik ajan kullanılmaktadır.Olumsuz bir deneyimin geri çağrılmasında M1 muskarinik reseptöralt tiplerinin önemli rol oynayabileceği öngörülmektedir. Buaraştırmanın amacı, TSSB’de kronik fluoksetin (FLU) (2.5 mg/gün; i.p) tedavisinin hem davranışsal hem de moleküler etkinliğinive farmakoterapinin sıçanlarda M1 muskarinik reseptör alt tipiekspresyonu üzerine muhtemel etkisini araştırmaktır.Gereç ve Yöntem: Deney tasarımında tüm gruplar rastgeleolarak seçilerek Kontrol, Stres ve Tedavi grupları oluşturulmuştur.Kronik FLU tedavisinin etkileri, sıçan hipokampüs ve frontalkorteksinde, M1 reseptörlerinin ekspresyon seviyeleri açısındandeğerlendirilmiştir.Bulgular: Sıçanlar deneyin son gününde (30.Gün) travmahatırlatıcılara maruz kaldıklarında, stres gruplarındaki anksiyeteindekslerinin kontrol grubuna göre belirgin bir şekilde arttığıgözlemlenmiştir (P

Programlanmış hücre ölümü olan apoptoz birçok fizyolojik süreçte aktif rol oynamaktadır. Apoptozun, büyüme faktörlerinin eksikliği, DNA hasarı ve birden fazla faktörü içeren çeşitli hücresel stresle aktive olan ‘hücre içi’ ve ölüm reseptörlerine ligandın bağlanmasıyla kaspazların aktive olduğu ‘hücre dışı’ olmak üzere iki yolağı vardır. Apoptotik hücre sayısı ile organizmanın sağlıklı olup olmadığı belirlenir. Apoptoz oranının azalması hücre sayısını arttırırken, apoptoz oranının artması hücre sayısını azaltarak dokularda tahribata neden olmaktadır. Apoptotik sinyallemede düzensizlik çeşitli hastalıklarda/bozukluklarda primer ya da sekonder rol oynamaktadır. Son yıllarda apoptozun nörodejeneratif hastalıklarla ilgili çalışmaları ön plana çıkmaya başlamıştır. Apoptotik sinyal yolaklarının daha iyi tanımlanması, pro- ve anti-apoptotik genlerin belirlenmesiyle, çalışmalar hız kazanmıştır. Travma Sonrası Stres Bozukluğu gibi nörodejeneratif bozukluklarda beyindeki yapısal ve fonksiyonel değişiklikler mitokondriyal stres ile ilişkilidir. Fizyolojik koşullarda hayati öneme sahip olan apoptoz, patolojik koşullarda mekanizmanın tetiklenmesine ve kontrolsüz hücre çoğalmasına yol açmaktadır. Hücre ölümünü engelleyen terapötik ilaçların geliştirilmesiyle apoptoz aracılı nörodejenaratif bozuklukların tedavisine yeni umutlar oluşacaktır., Apoptosis is programmed cell death, which actively occurs in many physiological processes. It can be triggered in two ways: (i) defects in growth factor, DNA damage, and other many factors that can cause cellular stress, which is an intracellular pathway, and (ii) ligand binding to death receptors and activation of caspases. The apoptotic cell count can be determined by the health of the whole organism. A higher apoptotic ratio can indicate a decrease in the number of cells and tissue damage, while a lower apoptotic ratio can indicate an increase in the number of cells. Irregularity in apoptotic signals can play primary or secondary roles in various diseases/disorders. Research on apoptosis depends on neurodegeneration has been initiated in the past few years. Definition of apoptotic signal pathways and apoptotic regulation and determination of pro- and anti-apoptotic genes are the main topics that have accelerated research on apoptosis. Neurodegenerative disorders such as post-traumatic stress disorder neuronal damage associated with changes in brain structure and function may be related to the mitochondrial stresses. In physiological conditions, apoptosis is crucial for the organism, while in pathological conditions, apoptosis can cause uncontrolled cell division. Development of therapeutic medicine that inhibits the cell death may be the new choice of treatment for neurodegenerative diseases/disorders.

BACKGROUND: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. METHODS: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90 degrees C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25 degrees C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. RESULTS: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. CONCLUSION: Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.

Amac: Post travmatik stres bozuklugunda (PTSD) iyonotropik glutamat reseptor (GluN1)’lerinin (GluN1) ve kalmodulinin birlikte etki ederek nitrik asit sentaz (NOS) aktivasyonu yaptigi bilinmemektedir.Gerec ve Yontem: Her iki cinsiyetten Sprague-Dawley sicanlari kirli kedi kumuyla saldirgan hayvan kokusuna maruz birakildiktan sonra, sicanlara yukseltilmis t labirenti deneyleri uygulanmistir. Deney sonrasi sicanlarin anksiyete endeksleri hesaplanmis ve kalmodulin, NOS ve GluN1 olcumleri icin hipokampus ve amigdala doku ornekleri Western Blot yontemi icin hazirlanmistir.Bulgular: Travmatize edilen sicanlarin anksiyete indeksleri kontrol grubuna gore anlamli olarak yuksek bulunmustur (p < 0.05). Dorsal hipokampus ve amygdaloid komplekste travmatize sicanlarin GluN1 ve kalmodulin duzeyleri azalmistir. NOS ekspresyonu her iki bolgede artis gostermesine karsin, amigdaloid kompleksteki artis (p < 0.001) dorsal hipokampuse gore (p < 0.05) istatiksel olarak daha anlamli bulunmustur.Sonuc: Saldirgan hayvan kokusu maruziyeti sicanlarda, PTSD semptomlari ve eksitotoksisite ile iliskili beyin alanlarinda nNOS ekspresyonunda artma ve GluN1 reseptorlerinde azalma ile birlikte uzun sure devam eden anksiyete iliskili etkilere neden olmaktadir. Sonuclarimiz, NOS aktivitesinin GluN1 disindaki nedenlerle arttigini gostermektedir

This review focuses on the methods of study that investigated the anxiolytic effects of new drugs with animal models. In a research setting, researchers investigate inquiry and recognition behavior changes of animals with anxiety in response to drug therapy. This forms the basis of a research. Although, “anxious” behaviors of rats do not exactly match the actual human behavior, they are still used as a model of human behavior. Several different stressor agents have been used including electric shocks, tilting the cage, olfactory bulbectomy, elevation of the setup, changing the lighting situation, under water trauma or exposure to predator materials. In these studies, generally the reaction to the stress is tested by observing the changes in the “anxious” behavior, cognitive impairment, fear and decreased social interaction. Frequently used models are; open field test, forced swimming test, social isolation, conflict tests, repeated stress test, tail suspension test, elevated maze tests, single prolonged test and chronical mild stress predator scane test. We explain various rat models and their properties and show how they are used to create anxiety with different stressor agents. Ease and repeatability of these models suggest that they are effective for studying drugs for the prevention and treatment of anxiety, Klinik öncesi çalışmalar kapsamında oluşturulan hayvan modelleri ile yeni ilaçların anksiyolitik etkileri araştırılmaktadır. Bu modellerde en sık kullanılan hayvanlar sıçanlar ve farelerdir. Anksiyete oluşturulan hayvanlarda; çevreyi araştırma ve tanıma davranışlarındaki değişiklikleri inceleyerek, ilaca verilen yanıta bu davranışlardaki değişimlerin saptanması araştırmaların temelini oluşturmaktadır. İnsanlarda görülen anksiyete davranışlarını tam olarak karşılamamakla birlikte hayvan modellerinde sıçanlardaki bu davranışlar modelin esasını oluşturmaktadır. Stres yaratan etken olarak; elektrik şoku, kafeslere eğim verilmesi, olfaktor bulbektomi, ortamın yükseltilmesi, aydınlatmanın değiştirilmesi, sosyal izolasyon, sualtı travmaları, saldırgan hayvanın kendisine ya da saldırgan hayvana ait ipuçlarına (saldırgana ait koku, tüy, idrar vb) maruz bırakma kullanılmaktadır. Oluşturulan strese karşı bu çalışmalarda genellikle aşırı irkilme, bilişsel bozukluklar, gelişmiş korku, düşük sosyal etkileşim gibi anksiyete davranışlarındaki değişimler ölçülmektedir. Sık kullanılan modeller arasında; açık alan, zorunlu yüzme, çatışma testleri, tekrarlayan stres uygulamaları, kuyruktan asma, yükseltilmiş labirentler, sosyal izolasyon, uzun süreli tek bir strese maruz bırakma, kronik hafif stres ve saldırgan ya da saldırgan ile ilgili ipuçlarına maruz bırakma testlerini saymak mümkündür.Bu derlemede, farklı stresörler ile anksiyete oluşturmada kullanılan sıçan modelleri tanımlanmaktadır. Modellerin özellikleri ve kullanım alanları gözden geçirildiğinde; kolay oluşturulabilir ve tekrarlanabilir oluşları, yeni geliştirilmekte olan ilaçların ya da mevcut benzer ilaçların anksiyeteyi önleme ve tedavi edici etkileri daha etkin olarak araştırılmaktadır.