Evaluating the Clinical Significance of Diazepam Binding Inhibitor in Alzheimer's Disease: A Comparison with Inflammatory, Oxidative, and Neurodegenerative Biomarkers.

INTRODUCTION: Alzheimer's disease (AD) is one of the pathologies that the scientific world is still desperate for. The aim of this study was the investigation of diazepam binding inhibitor (DBI) as a prognostic factor for AD prognosis. METHODS: A total of 120 participants were divided into 3 groups. Forty new diagnosed Alzheimer patients (NDG) who have been diagnosed but have not started AD treatment, 40 patients who diagnosed 5 years ago (D5YG), and 40 healthy control groups (CG) were included in the study. Levels of DBI, oxidative stress, inflammatory, and neurodegenerative biomarkers were compared between 3 groups. RESULTS: Plasma levels of DBI, oligomeric Aß, total tau, glial fibrillary acidic protein, α-synuclein, interleukin (IL) 1ß, IL6, tumor necrosis factor α, oxidative stress index, high-sensitive C-reactive protein, and DNA damage were found higher in D5YG and NDG as compared to CG (p < 0.001). On the contrary, plasma levels of total thiol, native thiol, vitamin D and vitamin B12 were lower in D5YG and NDG as compared to CG (p < 0.001). DISCUSSION: DBI may be a potential plasma biomarker and promising drug target for AD. It could help physicians make a comprehensive evaluation with cognitive and neurodegenerative tests.

Urotensin-II, oxidative stress, and inflammation increase in hypertensive and resistant hypertensive patients.

Objective: Hypertension is a multi-factorial process prevalent in developed as well as in developing countries. Urotensin-II, different antioxidants, free radicals, and inflammatory biomarkers play an essential role in the cardiovascular system. The aim of this study is to investigate Urotensin-II, oxidative stress, and inflammation markers in normotensive, hypertensive, and resistant hypertensive patients. Methods: Fifty resistance hypertensive (rHT) patients, 50 hypertensive patients, and 50 age gender matched normotensive controls (NT-control) were enrolled. Urotensin-II (UII), total oxidant status (TOS), total antioxidant status (TAS), native thiol (NT), total thiol (TT), disulfide (DIS), interleukin 1 beta (IL1ß), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), high sensitive c reactive protein (hsCRP), high-density lipoprotein (HDL) low-density lipoprotein (LDL), and total cholesterol (TC) were evaluated. Results: Serum levels of UII, IL1ß, IL6, TNFα, DIS, TOS, and OSI were found higher in rHT and HT as compared to NT-control (p < .001). On the contrary, serum levels of TT, TAS, and NT were lower in rHT and HT as compared to NT-control (p < .001). While TC, hsCRP, TOS, OSI, UII, IL1ß, IL6, and TNFα levels increase from HT to rHT group (p < .001); TAS and NT levels decrease from HT to rHT group (p < .001). Conclusions: UII levels, oxidative stress, and inflammation are higher in rHT and HT, while antioxidants and thiol levels are lower than the NT-control. Our study clearly showed that rHT and HT are more susceptible to impaired states of antioxidants, oxidative stress, and free radicals.

Time interval between E and E' waves can predict complicated clinical course in patients with acute pulmonary embolism.

PURPOSE: Acute pulmonary embolism is a life-threatening cardiothoracic emergency leading to right ventricle systolic and diastolic dysfunction. In the present study, we investigated the right ventricle diastolic function and its predictive value in patients with acute pulmonary embolism. MATERIAL AND METHODS: Were prospectively recruited in this study 621 patients diagnosed with acute pulmonary embolism between December 2015 and June 2019. Among them, 173 were excluded, leaving 448 patients for follow-up. Transthoracic echocardiography was performed for the evaluation of the right ventricle systolic and diastolic indices. At 30-day follow-up, the patients were allocated either into the benign or in the complicated clinical course group. RESULTS: The group with complicated clinical course had higher value of pulmonary artery systolic pressure (PASP), right/left ventricle diameter ratio, E-wave velocity, E/A ratio, A' wave velocity, E/E' ratio, and time interval between E and E' waves (P < .05), but lower values of tricuspid annular plane systolic excursion, A-wave velocity, isovolumetric relaxation time, deceleration time, E', and E'/A' (P < .05). Complicated clinical course was associated with shorter isovolumetric relaxation time (r = .564, P < .001), E/E' (r = .495, P < .001), and TE-E' (r = .596, P < .001). Receiver operator characteristic curve analysis showed that TE-E' had the largest area under curve (TE-E' 0.82, IVRT 0.77, E/E' 0.72). A cut-off value of TE-E' = 70 milliseconds had an 81.1% sensitivity and 71.4% specificity for the prediction of the complicated clinical course. CONCLUSION: The assessment of the right ventricle diastolic function could predict the complicated clinical course in patients with acute pulmonary embolism.

Assessment of Patients with Intracerebral Hemorrhage or Hemorrhagic Transformation in the VENOST Study.

INTRODUCTION: Cerebral venous and sinus thrombosis (CVST) may lead to cerebral edema and increased intracranial pressure; besides, ischemic or hemorrhagic lesions may develop. Intracerebral hemorrhages occur in approximately one-third of CVST patients. We assessed and compared the findings of the cerebral hemorrhage (CH) group and the CVST group. MATERIALS AND METHODS: In the VENOST study, medical records of 1,193 patients with CVST, aged over 18 years, were obtained from 35 national stroke centers. Demographic characteristics, clinical symptoms, signs at the admission, radiological findings, etiologic factors, acute and maintenance treatment, and outcome results were reported. The number of involved sinuses or veins, localizations of thrombus, and lesions on CT and MRI scans were recorded. RESULTS: CH was detected in the brain imaging of 241 (21.1%) patients, as hemorrhagic infarction in 198 patients and intracerebral hemorrhage in 43 patients. Gynecologic causes comprised the largest percentage (41.7%) of etiology and risk factors in the CVST group. In the CH group, headache associated with other neurological symptoms was more frequent. These neurological symptoms were epileptic seizures (46.9%), nausea and/or vomiting (36.5%), altered consciousness (36.5%), and focal neurological deficits (33.6%). mRS was ≥3 in 23.1% of the patients in the CH group. DISCUSSION AND CONCLUSION: CVST, an important cause of stroke in the young, should be monitored closely if the patients have additional symptoms of headache, multiple sinus involvement, and CH. Older age and parenchymal lesion, either hemorrhagic infarction or intracerebral hemorrhage, imply poor outcome.

Hepatic venous Doppler assessment can anticipate simplified pulmonary embolism severity index and right ventricle dysfunction in patients with acute pulmonary embolism.

PURPOSE: Acute pulmonary embolism (APE) is a life-threating cardiothoracic thromboembolic emergency in which right ventricle dysfunction (RVD) is a major concern. In the present study, we examined the hepatic veins (HVs) blood flow with pulsed-wave spectral Doppler ultrasonography to determine its relationship with the simplified pulmonary embolism severity index (sPESI) and the patient's RVD status. METHODS: We divided the 243 patients who met the inclusion criteria into two groups based on both their sPESI scores and their RVD status. Transthoracic echocardiography was performed to evaluate the RVD and the HVs within 1 hour after patient admission. The liver was evaluated using subcostal and intercostal echocardiographic windows in grayscale B-mode, and HVs were assessed using color and spectral Doppler assessment though the same echocardiographic windows. RESULT: A cut-off value of the systolic reverse flow velocity-time integral (SrVTI) = 2.2 cm carried a sensitivity and specificity of 84.29% and 74.89%, respectively, for the prediction of sPESI ≥ 1. A SrVTI cut-off value of 2.1 cm yielded a sensitivity and specificity of 83.03% and 73.91%, respectively, for the prediction of RVD. CONCLUSION: HV Doppler assessment could be a useful method for anticipating the sPESI and the presence of RVD in patients with APE. In addition, it may provide information regarding the hemodynamic impact of APE.

Behçet's disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study.

OBJECTIVE: This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçet's disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST). METHODS: VENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis. RESULTS: BD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%). CONCLUSIONS: BD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study.

AIM: Systemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics. MATERIAL AND METHOD: Among the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded. RESULTS: In total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up. CONCLUSIONS: SLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.

Pineal gland volume in schizophrenia and mood disorders.

BACKGROUND: The majority of patients with schizophrenia and mood disorders have disruptions in sleep and circadian rhythm. Melatonin, which is secreted by the human pineal gland, plays an important role in sleep and circadian rhythm. The aim of the present study was to evaluate and compare pineal gland volumes in patients with schizophrenia and mood disorders. SUBJECTS AND METHODS: We retrospectively evaluated the pineal gland volumes of 80 cases, including 16 cases of unipolar depression, 17 cases of bipolar disorder, 17 cases of schizophrenia, and 30 controls. The total pineal gland volume of all cases was measured via magnetic resonance images, and the total mean pineal volume of each group was compared. RESULTS: The mean pineal volumes of patients with schizophrenia, bipolar disorder, unipolar depression, and the controls were 83.55±10.11 mm(3), 93.62±11.00 mm(3), 95.19±11.61 mm(3) and 99.73±12.03 mm(3), respectively. The mean pineal gland volume of the patients with schizophrenia was significantly smaller than those of the other groups. CONCLUSIONS: Our data show that patients with schizophrenia have smaller pineal gland volumes, and this deviation in pineal gland morphology is not seen in those with mood disorders. We hypothesize that volumetric changes in the pineal gland of patients with schizophrenia may be involved in the pathophysiology of this illness.

Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey.

BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

Angiographic characteristics of coronary artery fistulas.

OBJECTIVES: Coronary artery fistula (CAF) in adults is a rare form of coronary artery anomaly. It is often diagnosed incidentally during coronary angiography. The aim of this study was to evaluate the clinical and angiographic characteristics of adult patients with CAF. STUDY DESIGN: We retrospectively reviewed the database of 70,850 patients who had undergone coronary angiography in five different invasive cardiology centers in the southeastern region of Turkey. Among them, 56 patients had CAF (39 males, 17 females, mean age: 63.7±10.4 years). Demographic data, clinical evaluation and cardiac catheterization reports were reviewed from the medical records. RESULTS: A total of 58 fistulas were detected in 56 patients; two patients (3.6%) had bilateral fistulas originating from both the left and right coronary artery. In our angiographic series, CAF prevalence was 0.08%. Dyspnea on exertion and/or angina pectoris was the most common symptom (69%). Fifteen patients (26.8%) had concomitant obstructive coronary artery disease. Coronary artery fistulas originated mainly from the left anterior descending artery (n=30, 51.7%). Others originated from the right coronary artery (n=15, 25.9%), circumflex artery (n=6, 10.3%), and right sinus of Valsalva (n=3, 5.2%). In four patients (n=4, 7.1%), multiple micro fistula were draining into the left ventricle. CONCLUSION: In our angiographic series, the prevalence of CAF was 0.08%, and the most common site of origin was the left anterior descending artery.

Development of Curcumin and Turmerone Loaded Solid Lipid Nanoparticle for Topical Delivery: Optimization, Characterization and Skin Irritation Evaluation with 3D Tissue Model.

Background: Curcuma longa L., commonly known as turmeric, is renowned for its therapeutic benefits attributed to bioactive compounds, namely curcumin (Cur) and aromatic turmerone (Tur), present in its rhizome. These compounds exhibit diverse therapeutic properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, the topical application of these compounds has a significant potential for inducing skin irritation. This study focuses on formulating solid lipid nanoparticle (SLN) carriers encapsulating both Cur and Tur for reduced irritation and enhanced stability. Methods: SLN formulations were prepared by a method using homogenization followed by ultrasonication procedures and optimized by applying response surface methodology (RSM). Results: The optimized SLN formulation demonstrated entrapment efficiencies, with 77.21 ± 4.28% for Cur and 75.12 ± 2.51% for Tur. A size distribution of 292.11 ± 9.43 nm was obtained, which was confirmed to be a spherical and uniform shape via environmental scanning electron microscopy (ESEM) images. The in vitro release study indicated cumulative releases of 71.32 ± 3.73% for Cur and 67.23 ± 1.64% for Tur after 24 hours under sink conditions. Physical stability tests confirmed the stability of formulation, allowing storage at 4°C for a minimum of 60 days. Notably, in vitro skin irritation studies, utilizing the reconstructed human epidermal model (EPI-200-SIT), revealed a significant reduction in irritation with the SLN containing Cur and Tur compared to nonencapsulated Cur and Tur. Conclusion: These findings collectively endorse the optimized SLN formulation as a favorable delivery system for Cur and Tur in diverse topical uses, offering enhanced stability, controlled release and reduced irritation.

Factors affecting seizure recurrence in the emergency department.

Background: Information on Emergency Department (ED) follow-up of patients presenting with epileptic seizures is limited. Objectives: It was planned to investigate the factors affecting the recurrence of epileptic seizures in the follow-up of patients presenting to the ED with the complaint of epileptic seizures. Materials and methods: This prospective, observational, single-center study was carried out in an adult population presenting to the ED. The study included patients older than 18 years of age presenting to the ED with the complaint of epileptic seizures. Results: Of the 205 patients included in the study, 68 (33.2%) had seizure recurrence during the 6 h. In the univariable analysis, advanced age, prolonged post-ictal duration, increased seizure duration, generalized tonic clonic seizure, alcohol consumption within past 24 h, hypertension, coronary artery disease, Alzheimer's disease, prior ischemic cerebrovascular disease, low Glascow Coma Scale (GCS), high glucose, high C-Reactive Protein, high phosphorus, low potassium, high blood urea nitrogen, high lactate, increased anion gap, high osmolarity were statistically significant in predicting recurrent seizure recurrence within 6 h. According to the logistic regression, postictal duration, GCS score, and age were independent predictors in our model. The cut-off value of postictal duration in predicting seizure recurrence at the highest sensitivity (66.2%) and specificity (89.8%) was 22.5 min. Conclusion: A prolonged postictal state, low GCS score, advanced age may be an indication of seizure recurrence. Therefore, patients with a long postictal duration, low GCS score, advanced age should be followed up more carefully in terms of recurrent seizures in the ED.

The Left Distal transradial access site could give a safe alternate site for transradial coronary intervention (The Litaunent Study).

Transradial Access (TRA) is the suggested method when performing coronary procedures. TRA has several advantages over the transfemoral approach, but also some restrictions. The present study compared the efficacy and safety of the traditional proximal transradial approach (pTRA) with a newer technique known as the distal transradial approach (dTRA) for performing a coronary angiography (CAG) and percutaneous coronary intervention (PCI). Patients (n = 700) were placed into one of two categories (dTRA or pTRA) based on a random technique. The primary endpoint was RAO at follow-up. The secondary endpoints included the time required for sheath insertion, the rate of successful sheath insertion, rate of successful completion of CAG and PCI, total procedure time, total fluoroscopy time, total radiation dose, total contrast volume used, pain perception (visual analog scale 0-10), and hemostasis duration. dTRA patients had more skin punctures, failed punctures, failed wiring, overlap of access sites, sheath insertion time, and pain evaluation scale, while the pTRA group had more hemostasis time and first-time cannulation. RAO and pseudoaneurysm (PseA) were lower in the dTRA group. In this randomized study, dTRA had lower RAO and PseA than pTRA. However, multicenter, larger-patient trials are needed to provide definitive evidence.

The Effect of the Vertebral Artery Stenosis on the Basilar Artery Tortuosity.

AIM: To investigate the effect of vertebral artery stenosis (VAS) on the basilar artery tortuosity. MATERIAL AND METHODS: A total of 158 patients (101 males; 57 females) were divided into two main groups depending on existence of the in the vertebral artery (VA). Then, these groups were divided into two sub-groups according to the stenosis severity. All these groups were compared via the following variables: the gender, age, stroke risk factors, and basilar artery deflection angle. RESULTS: The dominant VA was found more common on the left side; and most of the cases had an adverse directional correlation between the side of the dominant VA and basilar artery bending (p= 0.002). It was noticed that the mean value of the basilar artery deflection angle was higher in the patients with a VA stenosis rate below 70%. In the left VA, hypertension was found higher in the patients with VAS (92.3%, p= 0.012). Furthermore, C-shaped (n=63, 43%) was the most observing morphological change in the basilar artery (BA). CONCLUSION: Consequently, this study suggests that the VA stenosis below 70% may contribute to the BA tortuosity by affecting asymmetric VA flow.

Assessing cytotoxic activities, theoretical and in silico molecular docking calculations of phthalocyanines bearing cinnamyloxy-groups.

Cancer has been recognized as one of the deadliest diseases in the world in recent years. By chemically tailoring specific properties, anticancer agents can be prepared very effectively for the treatment of various cancer types. In this manner, as anticancer agents, a series of soluble metal-free and metallophthalocyanines carrying cinnamyloxy-groups at peripheral ß-positions have been prepared. All synthesized phthalocyanines were characterized by various spectroscopic approaches such as ultraviolet - visible (UV - Vis), Fourier transform infrared (FT-IR), and matrix-assisted laser deionization/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) techniques. These compounds are highly soluble in dimethyl sulfoxide (DMSO) and soluble in common organic solvents. The spectroscopic properties, cytotoxicity, and theoretical calculations of these complexes have been investigated. In cytotoxicity tests, compounds 1, 4, and 7 are the most active against HT-29 cell lines with IC50 values of 36.9 µM, 32.5 µM, and 51.1 µM, respectively. Also, the most and the least cytotoxic compounds against healthy CCD cell line is compounds 5 and 6 with the IC50 value of 13.4 µM and >250 µM, respectively. The PDB ID:4BQG target protein representing the HT-29 cancer cell line and the anti-cancer activities of phthalonitrile and its phthalocyanines were supported by molecular docking studies. Density Functional Theory (DFT) study supported the experimental results, including the spectral data, and implied that the compounds 5-7 are comparable by their characteristics, such as electronic properties, optical properties, electrostatic potentials, reactivity parameters, with the earlier studied compounds 2-4, which were successfully proved to be good candidates for cancer treatment.Communicated by Ramaswamy H. Sarma.

Cerebral venous sinus thrombosis associated with spontaneous intermittent cerebrospinal fluid rhinorrhea: a case report.

OBJECTIVES: To present a rare case of cerebral venous sinus thrombosis (CVST). CLINICAL PRESENTATION AND INTERVENTION: A 43-year-old woman presented with coma and was diagnosed as a case of CVST. She recovered in a few days with heparin treatment. Many possible risk factors for CSVT were negative in the patient but intermittent cerebrospinal fluid (CSF) rhinorrhea was accidentally noticed. Cerebral computed tomography and magnetic resonance imaging were done. The patient was diagnosed as having spontaneous intermittent CSF rhinorrhea due to a defect in the base of the skull. CONCLUSIONS: This case showed the importance of being aware that a defect in the base of the skull may lead to intermittent CSF rhinorrhea in patients with CVST.

Predictors of Symptomatic Hemorrhage After Endovascular Treatment for Anterior Circulation Occlusions: Turkish Endovascular Stroke Registry.

We evaluated the predictive factors of symptomatic intracranial hemorrhage (SICH) in endovascular treatment of stroke. We included 975 ischemic stroke patients with anterior circulation occlusion. Patients that had hemorrhage and an increase of ≥4 points in their National Institutes of Health Stroke Scale (NIHSS) after the treatment were considered as SICH. The mean age of patients was 65.2±13.1 years and 469 (48.1%) were women. The median NIHSS was 16 (13-18) and Alberta Stroke Program Early CT 9 (8-10). In 420 patients (43.1%), modified Rankin Scale was favorable (0-2) and mortality was observed in 234 (24%) patients at the end of the third month. Patients with high diastolic blood pressure (P<.05) had significantly higher SICH. SICH was significantly higher in those with high NIHSS scores (P<.001), high blood glucose (P<.001), and leukocyte count at admission (P<.05). Diabetes mellitus (DM) (OR 1.90; P<.001), NIHSS (OR 1.07; P<.05), adjuvant intra-arterial thrombolytic therapy (IA-rtPA) (OR, 1.60; P<.05), and puncture-recanalization time (OR 1.01; P<.05) were independent factors of SICH. Higher baseline NIHSS score, longer procedure time, multiple thrombectomy maneuvers, administration of IA-rtPA, and the history of DM are independent predictors of SICH in anterior circulation occlusion.

A. hierchuntica extract exacerbates genotoxic, cytotoxic, apoptotic and oxidant effects in B16F10 melanoma cells.

Melanoma is a highly malignant tumor caused by melanocytes. Even though melanoma represents just 3% of all skin malignancies, it represents 75% of deaths. Extracts of A. hierchuntica were reported to have anti-inflammatory, hepatoprotective, and anti-melanogenic activities. This study aims to investigate the dose-related relationship and selectivity of the toxic effects of A. hierchuntica extracts (AHE) on melanoma cells and provide a new option that can be used in the future treatment of melanoma. B16F10 Mus musculus malign melanoma cells and L929 Mus musculus healthy fibroblast cells were treated with root and leaf AHEs in a dose-dependent manner. Intracellular glutathione levels, mitochondrial membrane potential activity, apoptosis, genotoxicity, and cytotoxicity of AHE were evaluated. This study is probably the first study to show a significant apoptotic and genotoxic activity of AHE in selected B16F10 cancer cell lines. Mitochondrial membrane potential and glutathione activity of B16F10 and L929 melanoma cells decreased with increasing concentrations of both leaf and root AHEs. However, viability and reactive oxygen species levels showed selectivity especially the AHEs concentrations between 400 µg/mL and 500 µg/mL. This selectivity based on doses was also validated in apoptosis and genotoxicity between healthy and cancer cells (p < 0.001). The results showed that when looking at melanoma-specific, AHE could be a source of inspiration as an active ingredient in future treatment protocols. AHE can be recommended as potential nutraceuticals in the prevention of human melanoma cancer.

Investigation of the Genotoxic, Cytotoxic, Apoptotic, and Oxidant Effects of Olive Leaf Extracts on Liver Cancer Cell Lines.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the seventh most common cancer and the third leading cause of tumor-related deaths worldwide. Mechanisms underlying tumor onset, progression, and metastasis in the case of HCC have not been adequately studied. In this study, we aimed to investigate the genotoxic, cytotoxic, apoptotic and oxidant effects of olive leaf extract (OLE) on HCC cells. MATERIALS AND METHODS: H4IIE Rattus norvegicus hepatoma cells and Rattus norvegicus healthy liver clone-9 cells were treated with the increasing concentrations of OLEs (250-2000 ppm) in ethanol, acetone, dichloromethane, and methanol. ATP cell viability, intracellular reactive oxygen species generation levels, double staining test with acridine orange/ethidium bromide, comet assay, levels of interleukin 1-beta (IL-1ß), IL-6, and tumor necrosis factor alpha were measured. Significance was determined using ANOVA test. RESULTS: Apoptotic, genotoxic, cytotoxic, and oxidative effects of OLEs increased with the increasing concentrations as compared to controls in H4IIE cells (p<0.001). CONCLUSION: This is the first study to show a significant and selective cytotoxic activity of OLEs in the selected H4IIE cancer cell lines. OLEs could selectively increase the apoptotic damage and show anti-proliferative and pro-apoptotic properties against the H4IIE cells. They could be recommended as potential nutraceuticals in the prevention of cancer.

Headache as the sole presenting symptom of cerebral venous sinuses thrombosis: Subgroup analysis of data from the VENOST study.

OBJECTIVES: Headache is the most common complaint in cerebral venous sinus thrombosis (CVST) and it may sometimes be the only symptom in these patients. This retrospective and prospective study was an investigation of any differences in terms of clinical risk factors, radiological findings, or prognosis in patients with CVST who presented with isolated headache (IH) and cases with other concomitant findings (non-isolated headache [NIH]). METHODS: A total of 1144 patients from a multicenter study of cerebral venous sinus thrombosis (VENOST study) were enrolled in this research. The demographic, biochemical, clinical, and radiological aspects of 287 IH cases and 857 NIH cases were compared. RESULTS: There were twice as many women as men in the study group. In the IH group, when gender distribution was evaluated by age group, no statistically significant difference was found. The onset of headache was frequently subacute and chronic in the IH group, but an acute onset was more common in the NIH group. Other neurological findings were observed in 29% of the IH group during follow-up. A previous history of deep, cerebral, or other venous thromboembolism was less common in the IH group than in the NIH group. Transverse sinus involvement was greater in the IH group, whereas sagittal sinus involvement was greater in the NIH group. The presence of a plasminogen activator inhibitor (PAI) mutation was significantly greater in the IH group. CONCLUSION: IH and CVST should be kept in mind if a patient has subacute or chronic headache. PAI, which has an important role in thrombolytic events, may be a risk factor in CVST. Detailed hematological investigations should be considered. Additional studies are needed.