A novel insight into the neuroprotective effects of cannabidiol: maintained apelin/dopamine synthesis, NRF2 signaling, and AKT/CREB/BDNF gene expressions.

Neuroinflammation is a process associated with degeneration and loss of neurons in different parts of the brain. The most important damage mechanisms in its formation are oxidative stress and inflammation. This study aimed to investigate the protective effects of cannabidiol (CBD) against neuroinflammation through various mechanisms. Thirty­two female rats were randomly divided into 4 groups as control, lipopolysaccharide (LPS), LPS + CBD and CBD groups. After six hours following LPS administration, rats were sacrificed, brain and cerebellum tissues were obtained. Tissues were stained with hematoxylin­eosin for histopathological analysis. Apelin and tyrosine hydroxylase synthesis were determined immunohistochemically. Total oxidant status and total antioxidant status levels were measured, and an oxidative stress index was calculated. Protein kinase B (AKT), brain-derived neurotrophic factor (BDNF), cyclic­AMP response element­binding protein (CREB) and nuclear factor erythroid 2­related factor 2 (NRF2) mRNA expression levels were also determined. In the LPS group, hyperemia, degeneration, loss of neurons and gliosis were seen in all three tissues. Additionally, Purkinje cell loss in the cerebellum, as well as neuronal loss in the cerebral cortex and hippocampus, were found throughout the LPS group. The expressions of AKT, BDNF, CREB and NRF2, apelin and tyrosine hydroxylase synthesis all decreased significantly. CBD treatment reversed these changes and ameliorated oxidative stress parameters. CBD showed protective effects against neuroinflammation via regulating AKT, CREB, BDNF expressions, NRF2 signaling, apelin and tyrosine hydroxylase synthesis.

Lercanidipine ameliorated doxorubicin-induced neuroinflammation and maintained the expressions of choline acetyltransferase via enhancing the levels of PI3K/AKT/HIF1-α expressions.

BACKGROUND: Doxorubicin (DOX) may cause various neurological side effects in the brain. Lercanidipine (LRD) has antioxidant, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the potential benefits of. METHODS AND RESULTS: Lercanidipine in reducing doxorubicin-induced neuroinflammation and maintaining the expressions of choline acetyltransferase. Thirty-two adult Wistar albino female rats were divided into four groups as Control, DOX (20 mg/kg intraperitoneally), DOX + LRD 0.5 (0.5 mg/kg orally), and DOX + LRD2(2 mg/kg orally). Twenty-four hours after the last drug administration (9th day), brain tissues were taken for histopathological, immunohistochemical (choline acetyltransferase [CHAT], interleukin-10 [IL-10], and caspase-3 [Cas-3] staining), biochemical (total antioxidant status [TAS], total oxidant status [TOS], and oxidative stress index [OSI]), and genetic analyzes (PI3K/AKT/HIF1-α and IL-6 gene expressions). Histopathological analyses revealed hyperemia, slight hemorrhage, degeneration, neuronal loss, gliosis in the cerebellum, and neuronal loss in the brain cortex and hippocampus in the DOX group. According to other analyzes, decreased CHAT, PI3K, AKT, HIF1-α and increased IL-6, IL-10, Cas-3 expression were observed in the DOX group. CONCLUSIONS: Both LRD doses reversed all these findings, but LRD2 was observed to be more effective. In conclusion, we determined that LRD has potential therapeutic effect by reducing DOX-induced neuroinflammation, oxidative stress and apoptosis in brain tissues.

The ameliorative effects of cannabidiol on methotrexate-induced neuroinflammation and neuronal apoptosis via inhibiting endoplasmic reticulum and mitochondrial stress.

Methotrexate (MTX) is an antineoplastic agent and has neurotoxic effects. It exerts its toxic effect on the brain by triggering inflammation and apoptosis. Cannabidiol (CBD) is an agent known for its antioxidant, anti-inflammatory effects in various tissues. The aim of this study is to examine the protective effects of CBD treatment in various brain structures from MTX damage and to evaluate the effect of intracellular pathways involved in apoptosis. Thirty-two adult Wistar Albino female rats were divided into four groups as control, MTX (20 mg/kg intraperitoneally [i.p.]), MTX + CBD (0.1 mL of 5 mg/kg i.p.), and CBD (for 7 days, i.p.). At the end of the experiment, brain tissues collected for biochemical analyses as total oxidant status (TOS), total antioxidant status, oxidative stress index (OSI), histopathological and immunohistochemical analyses as tumor necrosis factor-α (TNF-α), serotonin, mammalian target of rapamycin (mTOR) staining, genetic analyses as caspase-9 (Cas-9), caspase-12 (Cas-12), C/EBP homologous protein (CHOP), and cytochrome-c (Cyt-c) gene expressions. In the histopathological and immunohistochemical evaluation, hyperemia, microhemorrhage, neuronal loss, and significant decreasing expressions of seratonin were observed in the cortex, hippocampus, and cerebellum regions in the MTX group. mTOR, TNF-α, Cas-9, Cas-12, CHOP, and Cyt-c expressions with TOS and OSI levels were increased in the cortex. It was observed that these findings were reversed after CBD application in all regions. MTX triggers neuronal apoptosis via endoplasmic reticulum and mitochondrial stress while destroying serotonergic neurons. The reversal of the pathological changes with CBD treatment proves that it has anti-inflammatory and antiapoptotic activity in brain.

Recent advances in triazoles as tyrosinase inhibitors.

The tyrosinase enzyme, which is widely found in microorganisms, animals and plants, has a significant position in melanogenesis, plays an important role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, neurodegeneration, etc. Therefore, with the wide potential application fields of tyrosinase in food, agriculture, cosmetics and pharmaceutical industries, which has become the target enzyme for the development of therapeutic agents such as antibrowning, anticancer, antibacterial, skin whitening, insecticides, etc., a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. The triazole ring, which has a broad spectrum of biological action, is of increasing interest in the synthesis of new tyrosinase inhibitors. In this review, tyrosinase inhibition effects, structure-activity relationships, enzyme inhibition kinetics and mechanisms of action of 1,2,3- or 1,2,4-triazole derivatives were investigated. The data gathered is anticipated to supply rational guidance and an influential strategy for the development of novel, potent and safe tyrosinase inhibitors for better practical application in the future.

Isolation, characterization and anticancer activity of secondary metabolites from Verbascum speciosum.

Herein, two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-TOF/MS). Antiproliferative activities of Aucubun (1) and Verbascoside (3) were tested against A-549 (human colon cancer), MDA-MD-453 (human breast cancer) and 3T3-L1 (mouse fibroblast)cell lines by XTT assay. In addition, the anticarcer mechanism of action of aucubin (1) was investigated on MDA-MB-453 cells for the first time. XTT result showed that both applied compounds exhibited antiproliferative effect at different dose ranges depending on the cancer type, as well as selectivity between cancer and healty cell lines. Flow cytometry analyzes revealed that aucubin (1) exerts its cytotoxic effect in MDA-MB-453 cells by directing cells to early apoptosis and inhibiting the P13K/AKT signaling pathway.

Synthesis of novel pancreatic lipase inhibitors: Biological investigation and in silico studies.

The targeted compounds which are Schiff base derivatives were prepared by reaction of 6-(4-phenyl-piperazin-1-yl)pyridine-3-ylamine with 2-hydroxy and 2,6-dichloro benzaldehyde. These compounds were isolated, purified and then spectrally characterized via FT-IR, 1H and 13C NMR, LC MS TOF, and TGA analysis where strong proofs confirmed the formation of the targeted product. The biological activity, which is pancreatic porcine lipase inhibition, of the compounds was investigated and Orlistat was used as standard drug. The compound 3 was found to be as potent as orlistat against PL enzyme with an IC50 value of 0.50 µM. The molecular docking studies were performed for both obtained compounds and orlistat against active side of porcine pancreatic lipase. Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analyzes were performed for pancreatic porcine lipase with compound 3, which showed potent inhibition according to the results of in vitro studies. Furthermore, The ADME and toxicity analysis of the compounds were examined using web-based online platforms, SwissADME and pkCSM. In the light of biological activity and in silico studies, the compound 3 can be a potential drug candidate with further studies.Communicated by Ramaswamy H. Sarma.

Design and synthesis of phenylpiperazine derivatives as potent anticancer agents for prostate cancer.

Novel thiourea (5a, 5b) and thiazolidinone derivatives (6a, 6b) were synthesized by hybridizing molecules starting from the compound 6-(4-phenylpiperazin-1-yl)pyridin-3-amine (4) which is known to show anticancer activity. The synthesis of the leading compound was carried out by using 1-(5-nitropyridin-2-yl)-4-phenylpiperazine (3) which was obtained by a novel method of the reaction of 2-chloro-5-nitropyridine (1) and N-phenylpiperazine (2). The structures of the compounds were confirmed using FTIR, 1 H NMR, 13 C NMR, HRMS spectroscopic methods and elemental analysis. The organic molecules were tested for their anticancer activities against prostate cancer (PC) cell lines: DU 145, PC-3 and LNCaP. As the compound 5a exerted the highest cytotoxic activity, IC50 concentrations of compound 5a were further investigated in terms of morphology, colony-forming ability, RNA expression, fragmented DNA and cell cycle distributions of PC cell lines. Overall data revealed that compound 5a treatment induces apoptosis and DNA fragmentation in PC cell lines and inhibits cell cycle progression resulting in the accumulation of cells in either the G1 or the S phases.

The Effect of Type D Personality on Quality of Life in Patients with Multiple Sclerosis.

INTRODUCTION: The Type D personality was reported as an important indicator of adverse clinical outcomes and quality of life in various diseases. The objective of this study was to investigate the relationships between the Type D personality and clinical features and the effect of Type D personality on quality of life in patients with multiple sclerosis (MS). METHODS: Seventy-four patients with MS participated in this study. Clinical parameters of the patients were recorded and disability was assessed using the Expanded Disability Status Scale (EDSS). Patients were examined with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Type D Scale (DS14), and 36-Item Short-Form Health Survey (SF-36). RESULTS: BDI and BAI scores were significantly higher and mental subscale of the SF-36 scores were significantly lower in Type D compared to nonType D (p<0.001, p=0.001, and p<0.001, respectively). The total DS14 scores were found to be positively correlated with EDSS, BDI, and BAI and negatively correlated with SF-36 mental subscale (p=0.02, p<0.001, p<0.001, and p<0.001, respectively). Multivariate linear regression analysis indicated that the total DS14 score was independently associated with the mental component of SF-36 (p<0.001). CONCLUSION: The Type D personality traits may worsen the quality of life, particularly the mental component, in patients with MS. Consequently, the assessment of MS patients by brief and valid DS14 may be valuable for clinical practice.

The Serum Levels of Resistin and Its Relationship with Other Proinflammatory Cytokines in Patients with Alzheimer's Disease.

OBJECTIVE: The present study aims to analyze the levels of resistin, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-18, and C-reactive protein (CRP) in patients with Alzheimer's disease (AD) and also investigate a potential relationship between resistin levels and TNF-α, IL-1ß, IL-6, IL-18, and CRP levels in patients with AD. METHODS: The study included fifty patients with AD and 30 healthy controls with normal cognitive functions. The serum resistin, TNF-α, IL-1ß, IL-6, IL-18, and CRP levels were assessed. We performed a Mini-Mental State Examination (MMSE) to evaluate the general cognitive performance. RESULTS: The mean serum resistin, IL-1ß, IL-18, and TNF-α levels were significantly higher in patients with AD compared with the controls (p=0.026, p=0.002, p=0.003, and p=0.038, respectively). The IL-6 and CRP levels did not differ between the groups (p=0.874 and p=0.941). The resistin levels were positively correlated with the levels of CRP and IL-18 (r=0.526, p＜0.001; r=0.402, p=0.004, respectively). MMSE scores and inflammatory markers were not correlated (p＞0.05 for all). CONCLUSION: Serum resistin levels were significantly increased and correlated with some inflammatory markers in AD patients, suggesting that resistin might play a role in the inflammatory process of AD.

P-wave dispersion in patients with Guillain-Barré syndrome.

Cardiac autonomic dysfunction assessed by the presence of arrhythmia, by the methods, such as heart rate variability or blood pressure variability, and by the electrocardiographic abnormalities is common in Guillain-Barré syndrome (GBS). The goal of present study was to analyze the P-wave dispersion (PWD), which is the non-invasive marker of atrial arrhythmia, in GBS patients and to compare those with healthy individuals. Thirty-five patients with GBS (mean age 53.6 ± 15.5 years) and 35 healthy controls (mean age 49.2 ± 14.1 years) were included to this study. Demographic and clinical information of the patients with GBS were assessed retrospectively. A 12-lead surface electrocardiogram was acquired from all participants. Minimum and maximum P-wave duration and PWD were measured in the patients with GBS and healthy controls. Maximum P-wave duration and PWD were significantly longer, and minimum P-wave duration was significantly lower in the patients with GBS rather than the control group (p = 0.037, p < 0.001, p = 0.007, respectively). GBS disability scores were positively correlated with the maximum P-wave duration (p = 0.015, r = 0.406) and PWD (p = 0.001, r = 0.525). We found that PWD was significantly prolonged in GBS patients compared with the controls. The increased PWD which is cheap, quick, non-invasive and feasible electrocardiographic marker may be related to increased risk for atrial fibrillation in patients with GBS.

UHPLC-ESI-MS/MS and GC-MS Analyses on Phenolic, Fatty Acid and Essential Oil of Verbascum pinetorum with Antioxidant, Anticholinesterase, Antimicrobial and DNA Damage Protection Effects.

This paper is the first phytochemical and ABTS cation radical decolorisation activity, cupric reducing antioxidant capacity, anticholinesterase and DNA damage protection effect of endemic Verbascum pinetorum (Boiss.) O. Kuntze. Phenolic profile of V. pinetorum were qualified and quantified by UHPLC-ESI-MS/MS analysis. Malic acid (47250.61±2504.28 µg/g) and luteolin (7651.96±527.98 µg/g) were found as most abundant compounds for metanol and acetone extracts, respectively. Fatty acid and essential oil compositions were determined by GC-MS analysis. The main components of fatty acid were found to be palmitic (27.1%) and stearic (22.1%) acids. The main compounds of the essential oil were cineole (16.9%) and α-selinene (16.4%). The acetone extract was found to be more active than BHT used as a standard in ß-carotene-linoleic acid test system. In DPPH free radical scavenging activity, the acetone and methanol extracts showed higher activity than BHT at all tested concentrations. The acetone, methanol and water extracts showed strong inhibition while the acetone extract showed better activity than BHT and α-tocopherol which were used as standards in ABTS cation radical scavenging and cupric reducing antioxidant capacity assays, respectively. All extracts were found to be inactive in antialzheimer activity. The acetone extract exhibited moderate antimicrobial activity against C. albicans. The methanol extract of V. pinetorum were found no significant effect on DNA cleavage protection.

Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion.

BACKGROUND: Stroke is one of the most common causes of death and the leading cause of disability in adults. Cerebral ischemia/reperfusion injury causes cerebral edema, hemorrhage, and neuronal death. AIMS: In post-ischemic reperfusion, free radical production causes brain tissue damage by oxidative stress. Pregabalin, an antiepileptic agent was shown to have antioxidant effects. The aim of this study was to evaluate the neuroprotective and antioxidant effects of pregabalin on ischemia and reperfusion in rat brain injury. STUDY DESIGN: Animal experimentation. METHODS: Male Wistar rats weighing (250-300 g) were randomly divided into six groups, each consisting of 6 rats: control (C), pregabalin (P), ischemia (I), pregabalin + ischemia (PI), ischemia + reperfusion (IR) and ischemia + reperfusion + pregabalin (PIR). Rats were initially pre-treated with 50 mg/kg/d pregabalin orally for two days. Then, animals that applied ischemia in I, PI, IR and PIR groups were exposed to carotid clamping for 30 minutes and 20 minutes reperfusion was performed in the relevant reperfusion groups. RESULTS: NR2B receptor levels were significantly lower in the PIR group in comparison to the IR group. In the PIR group, Thiobarbituric acid reactive substance (TBARS) level had statistically significant decrease compared with IR group. Glutathione peroxidase (GSH-PX) levels were also significantly increased in the PIR group compared with I, IR and control groups. In the PI and PIR groups, catalase (CAT) levels were also significantly increased compared with I and IR groups (p=0.03 and p=0.07, respectively). CONCLUSION: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future.

Is Retinal Nerve Fiber Layer Thickness Change Related to Headache Lateralization in Migraine?

PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in migraine patients with unilateral headache. METHODS: A total of 58 patients diagnosed with migraine headache consistently occurring on the same side and 58 age- and sex-matched healthy subjects were evaluated in this cross-sectional study. RNFL thickness was measured using spectral-domain optical coherence tomography, and the side with the headache was compared with the contralateral side as well as with the results of healthy subjects. RESULTS: The mean patient age was 33.05 ± 8.83 years, and that of the healthy subjects was 31.44 ± 8.64 years (p = 0.32). The mean duration of disease was 10.29 ± 9.03 years. The average and nasal RNFL thicknesses were significantly thinner on the side of headache and on the contralateral side compared to control eyes (p < 0.05, for all). Thinning was higher on the side of the headache compared to the contralateral side; however, this difference was not statistically significant. CONCLUSIONS: The RNFL thicknesses were thinner on the side of the headache compared to the contralateral side in the migraine patients with unilateral headache, but this difference was not statistically significant.

Changes in retinal nerve fiber layer thickness in patients with cerebral infarction: evidence of transneuronal retrograde degeneration.

We aimed to evaluate the thicknesses of the retinal nerve fiber layer (RNFL) in patients with cerebral infarction (CI) by using optical coherence tomography. This cross-sectional study evaluated 45 patients with CI (patient group) and 45 healthy subjects (control group). All subjects underwent a complete ophthalmic examination including optical coherence tomography. The average, temporal, nasal, inferior, and superior quadrant RNFL thicknesses and in each of 12 sectors around the optic nerve head were obtained. The side with the infarction was compared to the contralateral side among the patients with cerebral infarction, and their measurements were also compared to those of the control group. Patients who had CI only in the middle cerebral artery (MCA) and posterior cerebral artery (PCA) were included in this study. Correlations between the RNFL thicknesses and infarction features were also evaluated. The mean age of the patients was 61.6 ± 12.4 years, and the mean age of the controls was 59.6 ± 11.8 years (p = 0.65). Of the 45 patients with cerebral infarction, 35 (77.7 %) had infarction in the MCA territory, 10 (22.2 %) had infarction in the PCA territory and the mean duration of the disease was 20.2 ± 29.1 months. The average, superior, inferior, and nasal RNFL thicknesses were significantly thinner in both eyes of the patients with CI than in the eyes of the control group (p < 0.05). The average and inferior RNFL thicknesses were significantly more affected in the ipsilateral eyes than in the contralateral eyes (p < 0.031 and p < 0.006, respectively). The amount of reduction in the RNFL thicknesses was not correlated with the infarction features. Significant thinning of the RNFL in patients with CI may result from transneuronal retrograde degeneration. Optical coherence tomography may provide useful information to confirm the process of trans-synaptic retrograde degeneration.

A Case-Control Association Study of RANTES (-28C>G) Polymorphism as a Risk Factor for Parkinson's Disease in Isparta, Turkey.

Background. Recent studies have revealed that inflammatory processes are involved in the pathogenesis of Parkinson's disease (PD). Multiple lines of evidence have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. We have examined whether genetic polymorphisms at the genes encoding chemokines IL-8 (-251A>T), MCP-1 (-2518A/G), and RANTES (-28C>G) and chemokine receptors CCR2 (V64I) and CCR5 (-Δ32) were associated with sporadic PD risk in Isparta, Turkey. Method. The pilot case-control association study included 30 PD patients and 60 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. Their genotype and haplotype frequencies were compared statistically. Results. One SNP (-28C>G) in RANTES revealed a significant association with PD (P (allele) < 0.0001, p-trend = 0.0007). The risk allele (G) in the homozygous and dominant models (OR = 17.29 and 32.10, 95% CI = 0.86-347.24 and 1.74-591.937, resp.) suggests additional PD risk. The haplotype TGCAN from the IL-8 (-251A>T), MCP-1 (-2518A>G), RANTES (-28C>G), CCR-2 (V64I), and CCR-5 (-Δ32) has protective effect (OR = 0.08 [CI = 0.01-0.63], p = 0.019). Conclusions. Our data are the first indication of the role of RANTES (-28C>G) in PD risk.

The effect of cigarette smoking on retinal nerve fiber layer thickness in patients with migraine.

CONTEXT: Migraine is a frequent and disabling chronic neurological condition with complex pathophysiology. Both cigarette smoking and migraine may cause damage to the optic nerve. OBJECTIVE: The primary objective of this study was to investigate the effect of cigarette smoking on retinal nerve fiber layer (RNFL) thickness in patients with migraine. MATERIALS AND METHODS: Eighty-four consecutive patients diagnosed with migraine (34 smokers and 50 nonsmokers) and 66 age- and gender-matched healthy non-smoker controls were enrolled for this observational cross-sectional study. RNFL thickness was measured using spectral-domain optical coherence tomography (OCT) and then RNFL thickness in patients with migraine who smoke was compared to nonsmoking patients with migraine and healthy subjects. RESULTS: The average, superior, nasal and inferior RNFL thicknesses were significantly thinner in patients with migraine compared to the control group (p < 0.001, p = 0.02, p < 0.001 and p = 0.04, respectively). The average and inferior RNFL thicknesses were significantly reduced in smoker patients with migraine compared to the nonsmokers (p = 0.011, p = 0.045, respectively). Nonsmoker patients with migraine had significantly thinner average and nasal RNFL thicknesses than the control group (p = 0.001, p = 0.001, respectively). CONCLUSION: Cigarette smoking may cause significant RNFL thinning in patients with migraine. OCT may be a feasible technique for determination of smoking-induced ocular damage in patients with migraine.

The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis.

Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system that causes functional disability in young people. The aim of this study was to investigate the neutrophil-to-lymphocyte ratio (NLR) in patients with MS and the relationship between the NLR and the severity of the disease. One hundred and two MS patients (31 patients were in relapse; 71 patients were in remission) and 56 healthy controls were included. Complete blood counts as well as demographic and clinical data from MS patients were evaluated retrospectively. The NLRs were calculated for all participants and were compared; the cut-off value was also determined for the NLR and Expanded Disability Status Scale (EDSS). MS patients had a significantly higher NLR (p < 0.001) than the control group. The NLR levels were significantly higher in patients who were in relapse than patients in remission (p = 0.039). The cut-off value for the NLR to predict an MS diagnosis and activity were determined to be 2.04 and 3.90, respectively. The NLRs were directly correlated with erythrocyte sedimentation rate levels (r = 0.795, p < 0.001). Logistic regression analysis with dichotomous EDSS score showed that a high NLR was an independent predictor of the progression of disability. The NLR may be a biomarker that has simple, quick, inexpensive and reproducible properties in MS to predict patient's prognosis.

The Effects of Six-Month L-Thyroxine Treatment on Cognitive Functions and Event-Related Brain Potentials in Children with Subclinical Hypothyroidism.

OBJECTIVE: The aim of this study was to investigate the cognitive status of children with subclinical hypothyroidism (SH) before and after L-thyroxine (L-T4) treatment using event-related potentials (ERPs) and neuropsychological tests. METHODS: This prospective study was conducted on a series of 20 children with mild SH (free T4 normal and thyroid-stimulating hormone level within 5-10 µIU/L) who underwent clinical and cognitive assessment before L-T4 treatment and 6 months afterwards. The recordings of ERPs were done at the time of diagnosis and after 6 months of euthyroid state. Neuropsychiatric tests for attention, perception, close and remote memory were performed on all patients and on the control group which consisted of 20 healthy children of normal intelligence. RESULTS: While pretreatment verbal memory (VM) and verbal recall (VR) scores of the SH group were significantly lower than those of the control group (p=0.004 and 0.012, respectively), no significant differences between the post-treatment and control groups were found in these scores after 6 months of L-T4 treatment. Post-treatment VM and VR scores were significantly higher than the pretreatment scores in the SH group (p=0.008 and p=0.0001). There were no significant differences between the pre-and post-treatment values of electrophysiological evaluation in N1, P2, P3 latencies or P3 amplitude (p>0.05), although there was a significant decrease in N2 latency in the post-treatment group (p=0.03). CONCLUSION: SH affects cognition in children and L-T4 replacement therapy leads to normalization of cognitive functions. Neuropsychological tests can be used as complementary measures in the evaluation of children with SH. Determining the association between ERPs and SH would contribute to the comprehensive evaluation of these children.

Evaluation of retinal nerve fiber layer thickness in a patient with bilateral optic disc drusen

Optic disc drusen (ODD) is the accumulations of calcified hyaline-like material within the substance of the optic nerve head. Optic disc drusen, especially if it is bilateral, may mimic the clinical presentation of papilledema. Usually retinal nerve fiber layer (RNFL) thinning can be present in ODD. In this report we present uncommon RNFL changes in a patient with bilateral ODD. A 17-year-old male was referred by another center with a diagnosis of optic disc edema. The patient’s visual acuity, the slit-lamp examination and the intraocular pressures were normal in both eyes. On fundus examination, there were irregularly elevated discs bilaterally and the optic nerves appear with hazy disk margins. He did not have visual field defects in automated perimetry. Bilateral ODD were identified and confirmed by B-scan ultrasonography and optical coherence tomography (OCT) demonstrated 4 clock hours of RNFL thickening. Optic disc drusen may be misdiagnosed as papilledema. Thus, clinical suspicion of ODD is important in order to diagnose papilledema and prevents unnecessary interventions. Although most of eyes with ODD have normal or thinner RNFL thickness, some of these eyes can have thicker RNFL thickness.

As drusas do disco óptico (DDO) são depósitos de material hialino calcificado dentro da substância da cabeça do nervo óptico. Drusas do disco óptico, especialmente se for bilateral, podem apresentar o quadro clínico de edema de papila. Usualmente o espessamento da camada de fibras nervosas da retina (RCFN) podem estar presentes em DDO. Neste relato apresentamos o caso de um homem com 17 anos de idade que foi encaminhado por um outro centro, com o diagnóstico de edema do disco óptico. A acuidade visual do paciente, o exame de lâmpada de fenda e a pressão intraocular foram normais em ambos os olhos. No exame de fundo de olho havia discos elevados de forma irregular bilateralmente e os nervos ópticos com margens de disco nebulosas. Ele não tinha defeitos do campo visual em perimetria computadorizada. Drusas do disco óptico (DDO) bilateral foram identificados e confirmados pela ultrassonografia Bscan e tomografia de coerência óptica (TCO) que demonstraram 4 horas de relógio de RCFN com espessamento. As drusas do disco óptico podem ser diagnosticadas como papiledema. Assim, a suspeita clínica de DDO é importante a fim de evitar intervenções desnecessárias. Embora a maioria dos olhos com DDO têm espessura normal ou thinner RCFN, alguns desses olhos podem ter camada mais grossa na RCFN.

Riboflavin and vitamin E increase brain calcium and antioxidants, and microsomal calcium-ATP-ase values in rat headache models induced by glyceryl trinitrate.

The essential use of riboflavin is the prevention of migraine headaches, although its effect on migraines is considered to be associated with the increased mitochondrial energy metabolism. Oxidative stress is also important in migraine pathophysiology. Vitamin E is a strong antioxidant in nature and its analgesic effect is not completely clear in migraines. The current study aimed to investigate the effects of glyceryl trinitrate (GTN)-sourced exogen nitric oxide (NO), in particular, and also riboflavin and/or vitamin E on involved in the headache model induced via GTN-sourced exogen NO on oxidative stress, total brain calcium levels, and microsomal membrane Ca(2+)-ATPase levels. GTN infusion is a reliable method to provoke migraine-like headaches in experimental animals and humans. GTN resulted in a significant increase in brain cortex and microsomal lipid peroxidation levels although brain calcium, vitamin A, vitamin C, and vitamin E, and brain microsomal-reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and plasma-membrane Ca(2+)-ATPase values decreased through GTN. The lipid peroxidation, GSH, vitamin A, ß-carotene, vitamin C, and vitamin E, and calcium concentrations, GSH-Px, and the Ca(2+)-ATPase activities were increased both by riboflavin and vitamin E treatments. Brain calcium and vitamin A concentrations increased through riboflavin only. In conclusion, riboflavin and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system. However, the effects of vitamin E on the values seem more important than in riboflavin.