Risk factors for valproic acid induced hyperammonemia and its association with cognitive functions.

OBJECTIVE: Valproic acid (VPA)-induced hyperammonemia (VIH), is an increase in blood ammonia levels without any alteration of hepatic enzymes, which can occur during VPA treatment. We aimed to determine the prevalence rate and the risk factors for VIH and its association with cognitive functions. METHOD: A prospective, cross-sectional study was conducted. Patients aged between 18 and 64 who were on VPA treatment and who diagnosed with mood disorders or epilepsy were enrolled in this study (n = 107). For cognitive assessment, Serial 7's and Subjective Memory Complaints Questionnaire (SMCQ) were used. Blood samples were collected for blood VPA and ammonia levels along with other laboratory tests. RESULTS: 55,3% of the sample were considered as VIH. Blood ammonia level significantly correlates with VPA blood levels, total daily dose of VPA and total number of medications concurrently used, but no significant correlation was found between blood ammonia level and cognitive test scores. Gender, body weight, blood VPA levels and the total number of medications concurrently used significantly predicted blood ammonia levels (F(4,81) = 2670, p = 0,038, R2 = 0,116). CONCLUSION: VIH is relatively high in our sample. There is a dose-dependent association between VPA and blood ammonia level. No association was found between cognitive functions and hyperammonemia however with some limitations. Future, prospective cohort studies are needed.

Exercise increases leptin levels correlated with IGF-1 in hippocampus and prefrontal cortex of adolescent male and female rats.

It is known that regular aerobic exercise has positive effects on hippocampus and prefrontal cortex. We have previously have been able to demonstrate that aerobic exercise increased IGF-1 in hippocampus. Leptin, which is associated with cognitive functions, is also involved in fat metabolism and stimulates energy consumption. While it is known that leptin stimulates IGF-1 production in hepatocytes, little known is on the link between IGF-1 and leptin in brain during aerobic exercise. In this study, we investigated the effects of regular aerobic exercise on leptin, leptin receptor expression levels in hippocampus and prefrontal cortex. Additionally, we investigated the correlation of IGF-1 levels with leptin and leptin receptor expression. During the experiment, exercise group was run on a treadmill for 30min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. Leptin, leptin expression, IGF-1 levels and cell numbers increased in prefrontal cortex and hippocampus of exercise groups. Blood leptin levels increased in female rats in exercise group; whereas it did not change in male rats; blood IGF-1 levels were found to be increased in exercised male rats. There was a strong positive correlation between hippocampal leptin levels and hippocampal IGF-1 levels; also a strong positive correlation between hippocampal leptin receptor expression and hippocampal IGF-1. These results indicate that, increased leptin and leptin receptor expression are correlated with IGF-1 in regular aerobic exercised rats. Blood leptin and IGF-1 levels were also found to be associated with gender. Females had high blood leptin levels and males had high blood IGF-1 levels in the exercise groups.

Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: nerve growth factor Beta and vascular endothelial growth factor.

BACKGROUND: It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-ß) are important neurotrophic factors for male reproductive system. OBJECTIVE: We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-ß levels in diabetic rats. METHODS: Diabetes was induced by streptozotocin (STZ, 45 mg/kg/i.p.) in adult rats. Five weeks later testicular tissue was removed; testicular VEGF and NGF-ß levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsen's score. RESULTS: In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-ß were decreased in diabetic testes. Correlation between VEGF and NGF-ß levels was strong. CONCLUSION: These results suggest that the decrease of VEGF and NGF-ß levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-ß levels could be potential novel biomarkers for diabetes induced testicular damage.

Motivations of medical students towards psychiatry: a perspective from Turkey.

Recruitment in psychiatry has been an ongoing challenge worldwide; Turkey is no exception. In this article we have reviewed the issue from multiple aspects. Negative opinions on psychiatry among medical students have been associated with various matters, such as problems with scientific soundness, stigma, prestige and financial incentives. It has been reported that these negative opinions could be reversed by clinical exposure, improved knowledge base and increased affiliation with the field. Unfortunately, reversed attitudes do not have permanency. Considering that there has not been any study focusing on recruitment problems in Turkey, we attempted to provide a perspective by reporting the results of our study conducted with Turkish medical students. Attractive qualities of psychiatry were of particular interest. We found that brain research, neuroscience, philosophy, psychotherapy and academics are main areas of interest in psychiatry. We attempt to discuss our findings in view of current literature while noting current setbacks of psychiatry residency training in Turkey. We conclude that there exists a great need for working strategies in order to improve recruitment in psychiatry, addressing the stigma and correcting false beliefs such as treatment inefficacy or compromised scientific solidity.

Positive effects of aerobic exercise on learning and memory functioning, which correlate with hippocampal IGF-1 increase in adolescent rats.

It is already known that regular aerobic exercise during adolescent period improves learning and memory in rats. In this study, we investigated the effects of regular aerobic exercise on learning, memory functioning and IGF-1 levels. IGF-1 is known to have positive effects on cognitive functions in adolescent rats. Exercise group was separated into two different groups. First half was run on a treadmill for 30 min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. The second half was given free access to a running wheel (diameter 11.5 cm) which was connected to a digital counter and run on a treadmill for 6 weeks. Learning and memory functioning were found to be positively correlated with the exercise activity. Findings suggest increased neuron density in CA1 hippocampal region and dentate gyrus. Increased IGF-1 level was detected in hippocampus and blood serum, while IGF-1 level in liver tissue did not change with exercise activity. In conclusion, our findings indicate that learning and memory functioning were positively affected by voluntary and involuntary physical exercise which correlated increased hippocampal activity and elevated IGF-1 levels in adolescent rats.

Effect of acute and chronic exercise on oxidant-antioxidant equilibrium in rat hippocampus, prefrontal cortex and striatum.

Although regular physical exercise is beneficial to the body, it is well known that exhaustive exercise causes oxidative stress in muscle. Recent studies suggest that regular moderate physical exercise has the beneficial effects on brain. There is a little information regarding whether or not exercise could generate oxidative stress in the brain and the findings are conflicting. The aim of this study was to investigate the effects of acute and chronic exercise on thiobarbituric acid reactive substances, as an indicator of lipid peroxidation, in the hippocampus, which has a high concentration of glucocorticoid receptors, and prefrontal cortex and striatum, which have high dopamine content. Additionally we examined antioxidant enzyme activities, superoxide dismutase and glutathione peroxidase and nitrite-nitrate levels to assess the effects of reactive oxygen and nitrogen species. In this study it was shown that acute treadmill exercise at different strengths did not cause oxidative stress in prefrontal cortex, striatum and hypocampus regions of the brain. Regular treadmill exercise performed at different strengths was shown not to cause oxidative stress in prefrontal cortex, striatum and hippocampus regions of brain. As a result, we propose that acute and chronic exercise do not cause oxidant stress in prefrontal cortex, striatum and hippocampus and chronic exercise has a favorable effect on hippocampus, possibly by decreasing superoxide radical formation.