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Background: Precision medicine, which looks for high efficacy and low toxicity in therapies, has increased in popularity with omics technology. This work aims to discover novel and low-toxicity therapy options by examining the complex relationship between silodosin-induced side effects and the metabolomic profiles associated with its administration., Materials and Methods: The plasma samples of the control group and silodosin-treated rats were analyzed by LC-Q-TOF-MS/MS. Employing XCMS and MetaboAnalyst software, MS/MS data processed to detect compounds and investigate metabolic pathways. MATLAB 2019b was used for data categorization and multivariate analysis. A thorough comparison of METLIN and HMDB databases revealed 41m/z values with significant differences between the drug-treated and control groups (p <0.01 and fold analysis≥1.5)., Results: According to multivariate data analysis, 17-β-estradiol, taurocholic acid, L-kynurenine, N-formylkynurenine, D-glutamine, L-arginine, prostaglandin H2, prostaglandine G2, 15-keto-prostaglandin E2, calcidiol, thromboxane A2, 5'-methylthioadenosine, L-methionine and S-adenosylmethionine levels changed significantly compared to the control group. Differences in the metabolisms of glycerophospholipid, tyrosine, phenylalanine, arachidonic acid, cysteine and methionine, and biosynthesis of phenylalanine, tyrosine, and tryptophan, and aminoacyl-tRNA have been successfully demonstrated by metabolic pathway analysis. According to this study, vitamin D, D-glutamine, and L-arginine supplements can be recommended to prevent side effects such as fatigue, intraoperative floppy iris syndrome, blurred vision, and dizziness in the treatment of silodosin. Silodosin treatment negatively affected the immune system by affecting the kynurenine and tryptophan metabolism pathways., Conclusions: The study is a guide for silodosin treatments that offer low side effects and high therapeutic effect within the scope of precision medicine., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach., Methods: 38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid-liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument., Results: Significantly, altered metabolites were identified by the fold analysis and Welch's test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body., Conclusion: It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups., (© 2024. The Author(s), under exclusive licence to Japanese Association of Forensic Toxicology.)

With the increase in the education level of women, their level of representation in the professional professions and their presence in business life has increased. It has been inevitable that this situation would affect the socio-economic structure of societies and the health indicators of employed women. The aim of this study is to examine the effect of women's employment indicators on women's health indicators using the panel data analysis method. Two different econometric models were developed in the study. Model-1 predicts that a possible 1% increase in the female unemployment rate would result in a 0.06% decrease in the fertility rate. Model-2 estimates that a possible 1% increase in the female unemployment rate would lead to a 0.04% decrease in female-specific average life expectancy. Also, it is predicted that a possible increase of 1% in the total labor force participation rate of women can provide an increase of 0.04% in the average life expectancy of women. The results of the study indicate that the presence of women in the workforce directly impacts women's health indicators, particularly socio-economic indicators. Thus, there is a need to develop employment policies based on women's health in the employability of women.

Background: Air pollution is one of the biggest problems in societies today. The intensity of indoor and outdoor air pollutants and the urbanization rate can cause or trigger many different diseases, especially lung cancer. In this context, this study's aim is to reveal the effects of the indoor and outdoor air pollutants, and urbanization rate on the lung cancer cases., Methods: Panel data analysis method is applied in this study. The research includes the period between 1990 and 2019 as a time series and the data type of the variables is annual. The dependent variable in the research model is lung cancer cases per 100,000 people. The independent variables are the level of outdoor air pollution, air pollution level indoor environment and urbanization rate of countries., Results: In the modeling developed for the developed country group, it is seen that the variable with the highest level of effect on lung cancer is the outdoor air pollution level., Conclusions: In parallel with the development of countries, it has been determined that the increase in industrial production wastes, in other words, worsening the air quality, may potentially cause an increase in lung cancer cases. Indoor air quality is also essential for human health; negative changes in this variable may negatively impact individuals' health, especially lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gozlu, Senol, Cirakli, Aslan, Akbulut and Gokkaya.)

Objective: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery., Materials and Methods: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm., Results and Discussion: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient., Conclusion: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.

Introduction: The main purpose of the study is to examine the relationship between health expenditure indicators and economic growth in OECD countries., Methods: In this context, health expenditures and economic indicators data of 21 OECD countries were analyzed by the Driscoll-Kraay standard error approach within the scope of panel data analysis. While Gross Domestic Product (GDP) and income per capita were used as dependent variables, the amount of out-of-pocket health spending, per capita health expenditure, the amount of public health expenditure, the ratio of drug expenditures to gross domestic product, the share of current health expenditures in GDP were used as independent variables., Results: According to the results, in the model (Model 1) where real GDP level was used as the dependent variable, all health expenditure indicators were positively related to the economic growth. When the estimation results of Model 1 are examined, it is predicted that there will be an increase of 0.09% in GDP in case of a 1% increase in the share allocated to health services from GDP. In case of a 1% increase in the amount of out-of-pocket spending on healthcare, it is foreseen that there may be an increase of 0.04% in the real GDP. In the model (Model 2) where the per capita income variable is the dependent variable, it is seen that the increase in out- of-pocket health spending has a decreasing effect on the per capita income level, while the increase in public expenditures has an increasing effect on the per capita income level. From the findings of Model 2, it was found that if a 1% increase in the share of current health expenditures in GDP, there may be an increase of 0.06% in the amount of per capita income., Discussion: Concludingly, it is possible to say that that public resources allocated to health services play an important role in the economic growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beylik, Cirakli, Cetin, Ecevit and Senol.)

Chronic urticaria (CU) is a common disease characterized by the development of recurrent itchy blisters and/or angioedema lasting longer than 6 weeks. The evidence-based diagnosis of CU is described in the most recent urticaria guideline. Metabolomics has the potential to offer diagnostic biomarkers for the detection and prognosis of diseases and predict the efficacy and safety of pharmaceutical interventions. Determining the variation in metabolites found in the plasma of CU patients ( n  = 20) and 20 controls has therefore been the goal of this investigation. Samples were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry after applying acetonitrile precipitation. For the purpose of identifying and characterizing metabolites, the METLIN database was utilized. According to results, 21 metabolites were found to be significantly (VIP score > 0.7, p  < .05 and fold analysis >1.5) altered. Differentiations between each group were successful via both OPLS-DA and ROC analysis. While plasma allantoate, homogentisate, indole acetate, proline, phenylalanine levels decreased in CU patients compared to healthy subjects, tryptophan, spermidine, phenyl pyruvate, oleic acid, lysine, valine, ornithine, histidine, glutamate, leucine, kynurenine, hypoxanthine, tyrosine, glucose, creatine and cortisol levels were significantly increased. Diagnosis of CU could be achieved by evaluating the metabolic profile of patients.

Background: After a case of stroke, intracranial pressure (ICP) must be measured and monitored, and the gold standard method for that is through an invasive technique using an intraventricular or intraparenchymal device. However, The ICP can also be assessed through a non-invasive method, comprised of the measurement of the optic nerve sheath diameter (ONSD) through ultrasound (US)., Objective: To evaluate the ICP of patients who underwent wide decompressive craniectomy after middle cerebral artery (MCA) infarction via preoperative and postoperative ONSD measurements., Methods: A total of 17 patients, aged between 34 and 70 years, diagnosed with malignant MCA infarction with radiological edema and mid-line shift, who underwent decompressive surgery, were eligible. From the records, we collected data on age, sex, preoperative and postoperative Glasgow Coma Scale (GCS) scores, National Institutes of Health Stroke Scale (NIHSS) score, the degree of disability in the preoperative period and three months postoperatively through the scores on the Modified Rankin Scale (MRS), and the preoperative and postoperative midline shift measured by computed tomography (CT) scans of the brain., Results: Preoperatively, the mean GCS score was of 8 (range: 7.7-9.2), whereas it was found to be of 12 (range 10-14) on the first postoperative day ( p  = 0.001). The mean preoperative NIHSS score was of 21.36 ± 2.70 and, on the first postoperative day, it was of 5.30 ± 0.75 ( p  < 0.001). As for the midline shift, the mean preoperative value was of 1.33 ± 0.75 cm, and, on the first postoperative day, 0.36 ± 0.40 cm ( p  < 0.001). And, regarding the ONSD, the mean preoperative measurement was of 5.5 ± 0.1 mm, and, on the first postoperative day, it was of 5 ± 0.9 mm ( p  < 0.001)., Conclusion: The ocular US measurement of the ONSD for the preoperative and postoperative monitoring of the ICP seems to be a practical and useful method., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aim: Normal pressure hydrocephalus (NPH) is a rare disorder among the elderly, characterized by gait disorder, dementia, and urinary incontinence. Considering the rareness of NPH and a lot of other pathologies, such as Parkinson's disease, lumbar spinal stenosis, and even aging cause similar symptoms, NPH is an underdiagnosed entity. However, the percentage of misdiagnosis is not given in the literature., Material and Methods: In this study, patients diagnosed with NPH were retrospectively screened between 2015 and May 2019 in our clinical database and Ste-P formula was applied. Example cases showed that some of the patients receive inaccurate medical and surgical treatments before being diagnosed with NPH., Results: As a result of the study was seen that a few out of 29 patients confused dizziness with trunkal ataxia or imbalance due to gait abnormality. As the time between onset of complaints and diagnosis increased, the value approached "zero", and diagnosis became difficult., Conclusion: Every unnecessary operation carries serious risks that may threaten the life of the patient and decrease the quality of life. These surgeries and instrumentation materials used may also result to additional financial cost. Similarly, long-term use of Parkinson's and dementia medications has a serious economical burden on the insurance systems and is detrimental to the patient's health. Considering all these diagnoses and physiological conditions that can be easily confused with each other, we recommend in this article a new formula to reduce the possibility of misdiagnosis and treatment in patients with walking disorder.

This article presents the evaluation of anticholinesterase effects of aerial parts of Epilobium angustifolium , E. stevenii and E. hirsutum and isolated flavonoids from E. angustifolium , and quantification of the flavonoids by HPLC. Besides, the highest acetylcholinesterase inhibition was seen in the EtOAc sub-extracts of E. angustifolium and E. stevenii (36.51 ± 1.88 and 39.89 ± 3.09%, respectively), whereas EtOAc sub-extract of E. angustifolium had the best butyrylcholinesterase inhibition (62.09 ± 1.98%). Hyperoside showed strong inhibition activity on both enzymes. The active EtOAc sub-extract of E. angustifolium was quantitatively analyzed for their content of hyperoside (quercetin-3- O - β -D-galactoside) by HPLC. The content of hyperoside in EtOAc sub-extract of E. angustifolium was detected as 3.312%. The anatomical structures of the stem, leaf, sepal, petal, anther, and filament of E. angustifolium were investigated. The anatomical properties given in this study provide a description of E. angustifolium .[Formula: see text].

Aim: To investigate the effects of early surgery on electrocardiographic (ECG) parameters in patients with aneurysmal subarachnoid hemorrhage (SAH). We compared the parameters from ECGs performed preoperatively and on the 2nd and 8th days after surgery with those of normal individuals., Material and Methods: Eighteen patients with aneurysmal SAH (as the study group) and 22 healthy subjects (as the control group) were enrolled in this study. The demographics and ECG data of the participants were collected, and the groups were compared. The analyzed data included HR, QRS duration, Pmax, Pmin, P wave dispersion (PWD), QT, QTc, Tp-e, JT, JTc, Tp-e/QT, Tp-e/QTc, Tp-e/JT, and Tp-e/JTc. The preoperative and postoperative 2nd and 8th day values were compared., Results: The preoperative QT, QTc, JT, JTc, Pmax, and Pmin values of patients with aneurysmal subarachnoid hemorrhage were significantly higher than those of healthy subjects. There were no significant differences in the 2nd and 8th day ECG parameters of the groups., Conclusion: Early and successful surgery for SAH can alleviate ECG changes. This may decrease the requirement for cardiac interventions in these patients.

Purpose: To assess the possible relationship between blood thiamine pyrophosphate (TPP) concentration and stage of diabetic retinopathy (DR)., Methods: This comparative cross-sectional study included 80 patients with type 2 diabetes mellitus (T2DM) and 20 age- and gender-matched healthy controls. Diabetic patients were subclassified into four groups each consisting of 20 subjects: no DR, mild-moderate non-proliferative DR (mild-moderate NPDR), severe NPDR, and proliferative DR (PDR). Blood TPP concentration was assessed with high-performance liquid chromatography (HPLC) assay and was correlated with the stage of DR., Results: Mean blood TPP concentration was 80.2 ± 14.8 nmol/L in control group. It was, respectively, 69.85 ± 18.1, 64.95 ± 13.4, 61.9 ± 13.4 and 60.75 ± 14.3 nmol/L in no DR, mild-moderate NPDR, severe NPDR and PDR groups. For mild-moderate NPDR, severe NPDR and PDR groups, TPP concentrations were significantly lower compared with controls (p: 0.014, 0.002, 0.001, respectively). Mean TPP concentration for NPDR patients was higher than for PDR patients, but the difference was not significant (p: 0.478). ANOVA revealed a significant difference between TPP concentrations of groups (p: 0.001). Mean TPP concentration decreased with the stage of DR, and number of patients with thiamine deficiency increased gradually with the stage of DR. A negative correlation was found between the TPP level and occurrence of DR (p: 0.000)., Conclusion: The results suggest that lower blood TPP concentrations were associated with higher risk of DR. Thiamine might play an important role in the pathophysiology and progression of DR. Thiamine and its derivatives might represent an approach to the prevention and/or treatment of early DR.

ST segment elevation myocardial infarction (STEMI) is one of the most common global causes of cardiovascular disease-related death. Several metabolites may change during STEMI. Hence, analysis of metabolites in body fluid may be considered as a rapid and accurate test for initial diagnosis. This study has therefore attempted to determine the variation in metabolites identified in the serum of STEMI patients (n = 20) and 15 controls. Samples collected from the Cardiology Department, Medical Faculty, Ataturk University, were extracted by liquid-liquid extraction and analysed using liquid chromatography quadrupole time-of-flight mass spectrometry. The METLIN database was used for the identification and characterization of metabolites. According to Q-TOF/MS measurements, 231 m/z values, which were significantly different between groups (P < 0.01 and fold analysis >1.5) were detected. Metabolite identification was achieved via the Human Metabolome database. According to the multivariate data analysis, leucine, isoleucine, l-proline, l-alanine, glycine, fumaric acid, citrate, succinate and carnitine levels were decreased, whereas levels of propionic acid, maleic acid, butyric acid, urea, oleic acid, palmitic acid, lysoPC [18:2(9Z)], glycerol, phoshpatidylethanolamine, caffeine and l-lactic acid were increased in STEMI patients compared with controls. In conclusion, malonic acid, maleic acid, fumaric acid and palmitic acid can be used as biomarkers for early risk stratification of patients with STEMI., (© 2019 John Wiley & Sons, Ltd.)

Nephrotic syndrome (NS) is characterized by proteinuria in children. Steroid- resistant NS (SRNS) is defined by resistance to standard steroid therapy, and it continues to be one of the most common causes of chronic renal failure. Molecular studies have revealed specialized molecules in different regions of the podocytes that play a role in proteinuria. Mutations in NPHS2 that encode for podocin constitute a frequent cause of SRNS worldwide. This study aimed to screen for podocin mutations in Azerbaijani patients with SRNS. Our study included 21 pediatric patients with SRNS aged between 0 and 18 years and the same number of healthy control groups. Mutational analysis of the NPHS2 gene was performed using direct sequencing methods. Disease-causing mutations in the NPHS2 gene were detected in eight patients (38%). Thirteen patients (62%) had NPHS2 mutations without causing the disease. Two patients had p.Val290Met homozygous mutation; two had p.Arg229Gln homozygous mutations; and one each had p.Pro20Leu homozygote, p.Leu169Pro homozygote, p.Arg138Gln homozygote, and p.Arg168His homozygous mutations. When we correlated the NPHS2 mutation status with disease progression, there was a statistically significant increase in serum creatinine, proteinuria, and serum albumin values in patients with NPHS2 gene mutations compared to the group without mutation (P <0.05). Our study concludes that mutations of the NPHS2 gene (38%) are heterogeneous in Azerbaijani SRNS patients. Based on our results, we support a model in which ethnicity plays an important role in certain NPHS2 mutations. NPHS2 mutation analysis may help to better predict the course of the disease, remove unnecessary long-term immunosuppressive therapy, and develop specific treatment., Competing Interests: None

Objective: Osteoarthritis (OA), the most encountered arthritis form, result from degeneration of articular cartilage. Obesity is accepted as a significant risk factor for knee OA (KOA). In this study, it is aimed to determine the variation of metabolites between control and patients with KOA and observe the effect of obesity on KOA via untargeted metabolomics method., Methods: Serum samples of following groups were collected: patient group including 14 obesity (OKOA) and 14 non-obesity (NOKOA) (n = 28) and control group (n = 15) from orthopedics and traumatology policlinic. Serum proteins were denatured by acetonitrile and chromatographic separation of metabolites was achieved by LC/Q-TOF/MS/MS method. Data acquisition, classification, and identification were achieved by METLIN database. Cluster analysis was performed with MATLAB2017a-PLS Toolbox 7.2., Results: Obtained results showed that 244 (patient vs control) and 274 (OKOA vs NOKOA) m/z ratios were determined in accordance with LC/Q-TOF/MS/MS analysis. Multivariate data analysis was applied 41 and 36 m/z signal (p ≤ 0.01; fold analysis > 1.5) were filtered for patient vs control group and OKOA vs NOKOA, respectively. Twenty-one different metabolites were identified for patient vs control group and 15 metabolites were determined for OKOA vs NOKOA group., Conclusion: Acid concentration and oxidative stress agents were high in inflammation group and their levels were much higher in obesity. It is claimed that obesity cause oxidative stress and acidosis in arthritis patients. Valine was found to be the only BCAA molecule whose concentration has significantly different in KOA patients. The relation between KOA and obesity was firstly investigated with metabolomics method.

Olanzapine is an atypical antipsychotic drug from the thienobenzodiazepine family which displays efficacy in patients with schizophrenia and related psychoses. A novel LC/MS method was developed and validated for determination of olanzapine in schizophrenia patients' plasma. A liquid-liquid extraction procedure was carried out using 5 mL diethyl ether-diisopropyl ether mixture (1:1, v/v). Average recovery of the extraction procedure was 94.8%. Chromatographic separation was performed on reversed-phase C 18 column (250 × 2.0 mm, 5 μm) using mixture of deionized water (trifluoro acetic acid 0.1%)-acetonitrile (20:80, v/v) as mobile phase at a flow rate of 1 mL/min. Irbesartan was used as internal standart and total run time was 2.5 min. Mass spectrometric analysis were carried out in selective-ion montoring mode, and detected olanzapine at m/z 313.1 and IS at m/z 429.4 in all forms of the ions. The calibration curve of olanzapine was linear in the range 2-300 ng/mL (r 2  > 0.9993). The interday and intraday precisions (RSD) were <7.55%, and accuracy was >7.59% (n = 6). The proposed study was successfully validated with respect to the US Food and Drug Administration guidelines., (© 2018 John Wiley & Sons, Ltd.)

Parietin is one of the well-known anthraquinone compounds that can be extracted from Rheum ribes L. In this study, we aimed to investigate the effects of parietin isolated from Rheum ribes L on an in vitro wound model using human dermal fibroblast cells and compare its effectiveness against zinc. The antioxidant effect of parietin was determined by using the 1,1-diphenyl-2-picrylhydrazine (DPPH) method. Human dermal fibroblast cells were cultured in proculture medium and were kept until 100% confluence was achieved. The wound model was created by using a pipette tip. After that, different concentrations of parietin and zinc (final concentrations in the well to be 5-250 µM and 25-200 µM, respectively) were added into the medium. The proliferation-inducing effect on cell viability was determined by using MTT assay. Images of cells were taken at 0, 12, and 24 hours. According to the DPPH method, parietin exhibited have antioxidant activity. According to the MTT results, parietin exhibited significant proliferation-inducing effect on cell viability in a dose range of 5 to 10 M, and zinc showed significant proliferation-inducing effect on cell viability at dose 50 µM ( P < .05). In addition, the image of cell proliferation was also shown at the same doses at 24 hours. In this study, we claim that parietin induces cell proliferation at low doses in cases of dermal fibroblast loss. In conclusion, parietin as an alternative to zinc in wound healing could be used by clinicians in the future with more extensive studies.

Objectives: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples., Methods: Samples were deparaffinized and 20‑micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model., Results: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones., Conclusion: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).

Background: Atrial arrhythmias, particularly atrioventricular nodal reentrant tachycardia, can coexist with drug-induced type 1 Brugada electrocardiogram (ECG) pattern (DI-Type1-BrP). The present study was designed to determine the prevalence of DI-Type1-BrP in patients with atrioventricular accessory pathways (AV-APs) and to investigate the clinical, electrocardiographic, electrophysiologic, and genetic characteristics of these patients., Methods: One-hundred twenty-four consecutive cases of AV-APs and 84 controls underwent an ajmaline challenge test to unmask DI-Type1-BrP. Genetic screening and analysis was performed in 55 of the cases (19 with and 36 without DI-Type1-BrP)., Results: Patients with AV-APs were significantly more likely than controls to have a Type1-BrP unmasked (16.1 vs 4.8%, P = 0.012). At baseline, patients with DI-Type1-BrP had higher prevalence of chest pain, QR/rSr' pattern in V 1 and QRS notching/slurring in V 2 and aVL during preexcitation, rSr' pattern in V 1 -V 2 , and QRS notching/slurring in aVL during orthodromic atrioventricular reentrant tachycardia (AVRT) compared to patients without DI-Type1-BrP. Abnormal QRS configuration (QRS notching/slurring and/or fragmentation) in V 2 during preexcitation was present in all patients with DI-Type1 BrP. The prevalence of spontaneous preexcited atrial fibrillation (AF) and history of AF were similar (15% vs 18.3%, P = 0.726) in patients with and without DI-Type1-BrP, respectively. The prevalence of mutations in Brugada-susceptibility genes was higher (36.8% vs 8.3%, P = 0.02) in patients with DI-Type1-BrP compared to patients without DI-Type1-BrP., Conclusions: DI-Type1-BrP is relatively common in patients with AV-APs. We identify 12-lead ECG characteristics during preexcitation and orthodromic AVRT that point to an underlying type1-BrP, portending an increased probability for development of malignant arrhythmias., (© 2018 Wiley Periodicals, Inc.)

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1β, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1β and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

Choroid plexus tumors are rare intraventricular papillary neoplasms derived from choroid plexus epithelium, which account for approximately 2% to 4% of intracranial tumors in children and 0.5% in adults. Almost all choroid plexus carcinomas are seen in children and are extremely rare in adults. Headache, diplopia, and ataxia are the most common symptoms usually caused by mechanical obstruction of cerebrospinal fluid flow followed by hydrocephalus, regardless of tumor location. We present an illustrative case with 73 years old male patient who was consulted with headache to our neurosurgery department. In cranial computed tomography, there was a mass in 4(th) ventricle and we confirmed the mass with magnetic resonance imaging. After surgery had been performed, pathology specimen was diagnosed as choroid plexus carcinoma which was rarely seen in this age group.

was performed in both direct analysis of MSB and analysis of MN by converting MSB to MN with sodium carbonate. GC-FID method was carried out on the HP-5 capillary column GC-FID and HPLC-DAD methods were developed for determination of menadione (MN) and menadione sodium bisulphite (MSB). By means of each method, quantitative analysis of MSB in commercial pharmaceutical using nitrogen gas. HPLC-DAD method was achieved on the reversed phase C8 column by using a mobile phase consisting methanol and water. The calibration curves of GC-FID and HPLC-DAD for both analytes were linear in the same concentration range (0.5-20 μg/mL). Both methods were validated in terms of precision, accuracy, recovery and limits of detection (LOD) and quantitation (LOQ). Although LOD values of HPLC-DAD method (0.010 μg/mL for MN and 0.005 μg/mL for MSB) is lower than obtained values with GC-FID method (0.04 μg/mL for MN and 0.06 μg/mL for MSB), both methods gave similar and favorable results in terms of precision and accuracy. The Student's t-test was applied to investigate the significant of the different between the results of MSB determination with direct analysis of MSB and analysis of MN by converting MSB to MN by means of GC-FID and HPLC-DAD method in dosage form.

Micro RNAs (miRNA) negatively regulate protein-coding genes at the posttranscriptional level and are critical in tumorigenesis. Schwannomas develop from proliferation of dedifferentiated Schwann cells, which normally wrap nerve fibers to help support and insulate nerves. In this study, we carried out high-throughput miRNA expression profiling of human vestibular schwannomas by using an array representing 407 known miRNAs to explore the role of miRNAs in tumor growth. Twelve miRNAs were found to be significantly deregulated in tumor samples as compared with control nerve tissue, defining a schwannoma-typical signature. Among these miRNAs, we focused on miR-7, which was one of the most downregulated in these tumors and has several known oncogene targets, including mRNAs for epidermal growth factor receptor (EGFR) and p21-activated kinase 1 (Pak1). We found that overexpression of miR-7 inhibited schwannoma cell growth both in culture and in xenograft tumor models in vivo, which correlated with downregulation of these signaling pathways. Furthermore, we identified a novel direct target of miR-7, the mRNA for associated cdc42 kinase 1 (Ack1), with the expression levels of miR-7 and Ack1 being inversely correlated in human schwannoma samples. These results represent the first miRNA profiling of schwannomas and the first report of a tumor suppressor function for miR-7 in these tumors that is mediated by targeting the EGFR, Pak1, and Ack1 oncogenes. Our findings suggest miR-7 as a potential therapeutic molecule for schwannoma treatment, and they prompt clinical evaluation of drugs that can inhibit the EGFR, Pak1, and Ack1 signaling pathways to treat this tumor type.

Benign schwannomas are common tumors of the cranial and peripheral nerves, causing pain and loss of function. The development of effective therapy for these tumors has been hampered by the lack of relevant experimental in vivo models for convenient testing. Here, we describe a novel schwannoma model in which an immortalized human schwannoma cell line, HEI-193, established from an neurofibromatosis type 2 patient, has been stably transduced with fluorescent protein and luciferase reporters and implanted within the sciatic nerve of nude mice. These cells reliably formed a tumor within several weeks which had pathologic characteristics of schwannoma tumors. This model system will be useful for investigation of schwannoma biology and for preclinical assessment of therapeutic agents., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Meningiomas are among the most frequent tumors of the brain and spinal cord accounting for 15-20% of all central nervous system tumors and frequently associated with neurofibromatosis type 2. In this study, we aimed to unravel molecular meningioma tumorigenesis and discover novel protein biomarkers for diagnostic and/or prognostic purposes and performed in-depth proteomic profiling of meningioma cells compared to human primary arachnoidal cells. We isolated proteins from meningioma cell line SF4433 and human primary arachnoidal cells and analyzed the protein profiles by Gel-nanoLC-MS/MS in conjunction with protein identification and quantification by shotgun nanoLC tandem mass spectrometry and spectral counting. Differential analysis of meningiomas revealed changes in the expression levels of 281 proteins (P < 0.01) associated with various biological functions such as DNA replication, recombination, cell cycle, and apoptosis. Among several interesting proteins, we focused on a subset of the highly significantly up-regulated proteins, the minichromosome maintenance (MCM) family. We performed subsequent validation studies by qRT-PCR in human meningioma tissue samples (WHO grade I, 14 samples; WHO grade II, 7 samples; and WHO grade III, 7 samples) compared to arachnoidal tissue controls (from fresh autopsies; 3 samples) and found that MCMs are highly and significantly up-regulated in human meningioma tumor samples compared to arachnoidal tissue controls. We found a significant increase in MCM2 (8 fold), MCM3 (5 fold), MCM4 (4 fold), MCM5 (4 fold), MCM6 (3 fold), and MCM7 (5 fold) expressions in meningiomas. This study suggests that MCM family proteins are up-regulated in meningiomas and can be used as diagnostic markers.

Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of beta-catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target beta-catenin mRNA, thereby inhibiting its translation and blocking Wnt/beta-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of beta-catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/beta-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas.