Ocular pharmacokinetics and toxicity of nanoparticular acetazolamide: In vivo distribution and safety of PHBV-ACZ nanoparticle.

Diabetic macular edema (DME) is defined as fluid accumulation in the macular region, between the retinal layers, due to many diseases, especially diabetes. DME is one of the major complications of diabetic retinopathy (DRP). Carbonic anhydrase inhibitors (CAI) are a pharmaceutical agent used in different fields, especially glaucoma treatment. Acetazolamide (ACZ), which is a CAI, is an active substance that has been used off-label for many years in the treatment of macular edema due to diabetes and many other diseases. The low solubility and bioavailability of ACZ limit its use in the treatment of DME. In this study, a nanoparticulate formulation was developed that would increase the solubility and bioavailability of ACZ and allow it to be administered intravitreally. ACZ was loaded on poly(3-hydroxybutyrate-co-3-Hydroxyvalerate) (PHBV) nanoparticles and the loading efficiency was 71.58 ± 1.22%. Toxicity of nanoparticles after intravitreal application was evaluated with anterior segment and posterior segment examination findings, intraocular pressure (IOP) measurements and electrophysiological tests. At the end of the 3-month follow-up, electroretinography (ERG) measurements demonstrated that ACZ loaded PHBV (PHBV-ACZ) nanoparticles did not cause loss of function in retinal cells. On histological examination, rare degenerative changes were observed in several cell groups. In addition, pharmacokinetic studies were performed to determine the tissue distribution of ACZ at various periods. ACZ was identified in vitreous humor and retina at the highest concentration. Based on our results, the prepared nanoparticle formulation can release long-term CAI for DRP therapy and accordingly can reduce the need for monthly intravitreal injections.

Molecular investigation of Haemoproteus and Plasmodium species of some raptors in Hatay province: new CytB lineages for raptors of Accipitriformes in Turkey.

Accipitriform raptors are significant indicators of biodiversity and environmental health. Currently, most of the studies on avian haemosporidian parasites are on passerine birds, and data on raptors is constricted, with similarities both around the world and in Turkey. This study aimed to investigate the presence of Haemoproteus and Plasmodium spp. in raptors by microscopy and nested PCR technique. The study material consisted of 47 accipitriform raptors (Buteo buteo: 14, Buteo rufinus: 7, Clanga pomarina: 8, Circaetus gallicus: 12, Milvus migrans: 6). The prevalence of haemosporidian infection was 12.8% (6/47, 1 from Buteo buteo, 4 from Clanga pomarina, 1 from Milvus migrans) microscopically and 14.9% (7/47) molecularly. One Circaetus gallicus, microscopically found to be negative, probably due to low parasitemia, was molecularly found to be positive. All PCR-positive amplicons were bidirectionally sequenced, and the identification of lineages of the isolates and phylogenetic analysis were performed using the MalAvi and GenBank databases. The study revealed H-MILANS02 lineage in Buteo buteo, H-MILANS02 and P-CIAE1 lineages in Clanga pomarina, P-GRW06 lineage in Circaetus gallicus, and P-RTSR1 lineage in Milvus migrans, respectively. While this study removes the uncertainty regarding the reporting of the H-MILANS02 lineage in Turkey, it is also the first report to reveal 3 different Plasmodium spp. CytB lineages in raptors. Moreover, the fact that the P-GRW06 lineage (Plasmodium elongatum) detected in passerine birds was detected in a raptor, Circaetus gallicus, draws attention to the need for further investigations on host-parasite interaction and gives clues about the host-shifting ability of this parasite.

The Initial Part of Polymorphic Ventricular Tachycardia as a Clue for the Sustainability of Tachycardia and Ablation Success: A Varying Degree of Purkinje-Myocardial Complicity?

The cardiac Purkinje system is capable of very rapid burst activity suggestive of its potential role in being a driver of polymorphic ventricular tachycardia (VT) (PMVT) or ventricular fibrillation (VF). It plays a pivotal role, however, not only in the triggering of but also the perpetuation of ventricular arrhythmias. A varying degree of Purkinje-myocardial complicity has been blamed in determining not only the sustained or non-sustained nature of PMVT but also the pleomorphism of the non-sustained runs. The initial part of PMVT before cascading to the whole ventricle to establish disorganized VF can give important clues for ablation of PMVT and VF. We present a case of an electrical storm after acute myocardial infarction that was successfully ablated after identifying Purkinje potentials that triggered polymorphic, monomorphic, and pleiomorphic VTs and VF.

Utilizing linkage-specific ethyl-esterification approach to perform in-depth analysis of sialylated N-glycans present on milk whey glycoproteins.

Glycosylation of milk whey proteins, specifically the presence of sialic acid-containing glycan residues, causes functional changes in these proteins. This study aimed to analyze the N-glycome of milk whey glycoproteins from various milk sources using a linkage-specific ethyl esterification approach with MALDI-MS (matrix-assisted laser desorption/ionization-mass spectrometry). The results showed that the N-glycan profiles of bovine and buffalo whey mostly overlapped. Acetylated N-glycans were only detected in donkey milk whey at a rate of 16.06%. a2,6-linked N-Acetylneuraminic acid (a2,6-linked NeuAc, E) was found to be the predominant sialylation type in human milk whey (65.16%). The amount of a2,6-linked NeuAc in bovine, buffalo, goat, and donkey whey glycoproteomes was 42.33%, 44.16%, 39.00%, and 34.86%, respectively. The relative abundances of a2,6-linked N-Glycolylneuraminic acid (a2,6-linked NeuGc, Ge) in bovine, buffalo, goat, and donkey whey were 7.52%, 5.41%, 28.24%, and 17.31%, respectively. Goat whey exhibited the highest amount of a2,3-linked N-Glycolylneuraminic acid (a2,3-linked NeuGc, Gl, 8.62%), while bovine and donkey whey contained only 2.14% and 1.11%, respectively.

Elements in Mediterranean mussels from Istanbul and exposure assessment.

In this study, concentrations of elements were determined in edible tissues of Mytilus galloprovincialis by means of inductively coupled plasma mass spectrometry (ICP-MS). The mean levels (mg kg-1) of 0.67 for Cd, 6.9 for As, 0.79 for Pb, 2 for Ni, and 42.6 for Zn exceeded the maximum limits in the digestive glands. Also, the mean concentrations of Cd and As in muscle and of Cd and Ni in gills were above the maximum limits. The highest value was found for As in a digestive gland, with 65.4% of the Provisional Tolerable Weekly Intake. In addition, the lowest percentage belonged to Zn with 0.2% of PTWI in muscles and 0.3% of PTWI in gills of the mussels. Mercury concentrations were well below legal limits.

Chemometrics assisted untargeted metabolomic analysis to explore metabolic alterations in chronic urticaria via LC/Q-TOF/MS/MS.

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.

Determination and pharmacokinetic study of riociguat by UPLC-MS/MS in human plasma.

Pulmonary hypertension (PH) is frequent in the general population and is linked to an increased risk of death. Riociguat is a kind of endothelin receptor antagonist that is often used to treat PH. For pharmacokinetic studies and the determination of riociguat in PH patients, a new, quick, easy, and sensitive UPLC-MS/MS approach was designed and validated. Riociguat and irbesartan (IS) were detected using ESI in positive ion and multiple reaction monitoring mode, respectively, by monitoring the mass transitions m/z 423.0 â†’ 391.0 and 429.1 â†’ 206.9. A reverse-phase C18 column (5 µm, 4.6 × 150 mm) was used with an isocratic mobile phase of water containing 0.1 % formic acid-acetonitrile (25:75, v/v) at a flow rate of 1 ml/min for chromatographic separation. In the range of 5-400 ng/ml, the calibration curve was linear and had a good correlation coefficient (0.9972). This is the first UPLC-MS/MS technique that has been developed and validated for determining riociguat from human plasma. The developed analytical method was extensively validated for linearity, selectivity, specificity, accuracy, precision, sensitivity, stability, matrix effect and recovery, according to FDA criteria. The devised approach was successfully used for a pharmacokinetic research and riociguat determination in PH patients.

Coronary sinus collapsibility index and inferior vena cava collapsibility index can predict right atrial pressure in patients undergoing right heart catheterization.

BACKGROUND: The aim of the study is to investigate the relationship between the diameters and collapsibility indices of coronary sinus (CS) and inferior vena cava (IVC) and invasively measured right atrial pressure (RAP), and to determine whether these parameters have predictive value on RAP. METHODS: A total of 136 patients undergoing right heart catheterization due to pulmonary arterial hypertension were included in the study prospectively. CS diameters, IVC diameters, CS collapsibility index (CSCI), and IVC collapsibility index (IVCCI) were measured by echocardiography before catheterization. Pearson correlation analysis was used to compare the parameters. Receiver operating characteristics (ROC) curve analysis was used to determine the predictive value of the CS and IVC collapsibility indices in predicting RAP. RESULTS: Patients were divided into two groups as invasively measured RAP≥10 mm Hg (n:57) and RAP < 10 mm Hg (n:79). In the group with RAP≥10 mm Hg, IVC and CS diameters were higher than in the group with RAP < 10 mm Hg, while the IVCCI and CSCI were lower (p < 0.001). A negative correlation was observed between CSCI and IVCCI and RAP. Also, a positive correlation was observed between CSCI and IVCCI. Optimal cut-off value for IVCCI was 46.1 with a sensitivity of 75%, and specificity of 79.7%. Optimal cut-off value for CSCI was 39.2 with a sensitivity of 75.4%, and specificity of 88.6%. CONCLUSION: CS and IVC diameters and collapsibility indices measured by echocardiography were found to be associated with invasively measured RAP, and may be used together for estimating RAP.

Evaluation of Serum Trace Element Levels and Biochemical Parameters of COVID-19 Patients According to Disease Severity.

While the COVID-19 disease progresses mildly or asymptomatically in some people, its progression is severe and symptomatic in others, and it is an issue that requires a scientific response regarding the disease. The present study includes 60 people infected with COVID-19, and the cases were divided into the following groups: asymptomatic, mild, moderate, and severe. Serum Zn, Se, and Cu levels of these groups were analyzed by ICP-MS. All measurements in the patients were compared with those of 32 healthy individuals. When the patient group is compared with the control group, the serum Zn and Se concentrations were statistically low (p < 0.001) in the patient group. Serum Zn level decreased significantly in 4 different patient groups compared to the control group. Although the serum Se level decreased in all four patient groups compared to the control group, the change in Se level was statistically significant only in the severe and mild patient groups. This study examined serum Zn, Se concentrations, and biochemical parameters in patients with different severity of COVID-19, compared them with healthy individuals, and revealed new targets for diagnosis and treatment by revealing those data that may be important.

Evaluation of Iron and Zinc Contents of Some Fish Species.

In this study, Fe and Zn contents in the muscle of different fish species (Engraulis encrasicolus, Trachurus trachurus, Mullus barbatus, Mugil cephalus, Pomatomus saltatrix, Dicentrarchus labrax, Scomber scombrus, Sparus aurata) were determined using flame atomic absorption spectrometry (FAAS). The highest Fe and Zn contents among studied fish species were found in Engraulis encrasicolus (7.13 ± 0.19 mg/kg) and Sparus aurata (11.00 ± 0.28 mg/kg). The lowest Fe and Zn contents were determined in Dicentrarchus labrax (3.12 ± 0.09 mg/kg) and Pomatomus saltatrix (5.50 ± 0.05 mg/kg). Moreover, the results were evaluated considering the estimated daily intakes (EDI) of these elements for adults. The estimated daily intakes were varied from 0.0101 to 0.0231 mg/kg bw/day for Fe and 0.0178 to 0.0357 mg/kg bw/day for Zn in fish species. In addition, the hazard quotient (HQ) and the hazard index (HI) values were calculated for risk assessment, and it was determined that these values were below 1 for fish species.

Evaluation of genetic diversity by morphological, biochemical and molecular markers in sour cherry genotypes.

BACKGROUND: Turkey's ecological and geographical diversity allows the cultivation of most plant species that have economic importance throughout the country. One of these species, sour cherry, is among the stone fruits that are very important for human health. This study aimed to determine genetic diversity of 21 sour cherry genotypes grown from seed in Kelkit Valley and standard Kutahya cultivars. METHODS AND RESULTS: Morphological, biochemical, and molecular marker techniques [ISSR (Inter Simple Sequence Repeat)] was used to determine genetic diversity. G11 in terms of fruit characteristics, particularly weight with 4.81 g, and G20 in terms of leaf width produced better results than the other genotypes with 40.10 mm. Molecular marker analysis, a total of 70 bands were obtained from 12 ISSR primers and 49 of them were polymorphic. The mean polymorphism rate in the study was 70%, and the DICE's similarity coefficient of genotypes differed between 0.81 and 0.95. Polymorphism percentages of the ISSR primers varied from 20 to 100%. In biochemical analyzes, G17 with 140.18 mg QE/100 g in total flavonoids content, G19 with 208.63 mg GAE/100 g in total phenolics content, G19 with 8.33 mg cyn-3-gluc/100 g in total anthocyanin content compared to other genotypes prominent genotypes. CONCLUSION: The use of the obtained results in breeding studies to be carried out on this species, as well as the detection and protection of gene sources, may be beneficial for researchers.

The serum amino acid profile in COVID-19.

The pandemic of the coronavirus disease (COVID-19) caused by SARS-CoV-2 affects millions of people worldwide. There are still many unknown aspects to this infection which affects the whole world. In addition, the potential impacts caused by this infection are still unclear. Amino acid metabolism, in particular, contains significant clues in terms of the development and prevention of many diseases. Therefore, this study aimed to compare amino acid profile of COVID-19 and healthy subject. In this study, the amino acid profiles of patients with asymptomatic, mild, moderate, and severe/critical SARS-CoV-2 infection were scanned with LC-MS/MS. The amino acid profile encompassing 30 amino acids in 142 people including 30 control and 112 COVID-19 patients was examined. 20 amino acids showed significant differences when compared to the control group in COVID-19 patient groups with different levels of severity in the statistical analyses conducted. It was detected that the branched-chain amino acids (BCAAs) changed in correlation with one another, and L-2-aminobutyric acid and L-phenylalanine had biomarker potential for COVID-19. Moreover, it was concluded that L-2-aminobutyric acid could provide prognostic information about the course of the disease. We believe that a new viewpoint will develop regarding the diagnosis, treatment, and prognosis as a result of the evaluation of the serum amino acid profiles of COVID-19 patients. Determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker. Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols.

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.

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

OBJECTIVE: Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS: The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION: The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.

A Sensitive UPLC-MS/MS Method for the Determination of Flurbiprofen in Rat Plasma: Application to Real Sample.

For the quantification of flurbiprofen in rat plasma, a simple UPLC-MS/MS method with high sensitivity and short retention time for flurbiprofen was developed and validated using specific parameters. Etodolac was used as internal standard. The transitions (precursor to the product) of flurbiprofen and internal standard were obtained using the electrospray ionization in the negative ion multiple reaction monitoring mode, 243.2 â†’ 199.2, 286.2 â†’ 212.1, respectively. For chromatographic separation, C18 column was used for the stationary phase and gradient elution was used for the mobile phase. This mobile phase consisted of a methanol (A) and a 5 mM ammonium formate solution (B), which varied at a flow rate of 0.4 mL/min. For flurbiprofen, LLOQ was determined as 5 ng/mL. Quantification of flurbiprofen in the rat plasma with a linear calibration curve of 5-5000 ng/mL (r > 0.9991 for plasma) is possible with a retention time of 1.89 min. The total analysis time of the method was 3 min. The proposed method was validated. The intraday and inter-day precision (RSD%) and accuracy (RE%) were within 10% in all cases for flurbiprofen. The stability of flurbiprofen was evaluated under conditions such as short-term, long-term, autosampler and freeze/thaw. After method validation, flurbiprofen was succesfully quantified in real rat plasma samples.

Differential N-glycosylation profiling of formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma tissues using MALDI-TOF-MS.

Invasive ductal carcinoma (IDC) is the most common type of breast cancer. As dynamic changes of the glycome are closely associated with complex diseases, they have become a focal point of cancer research involving predictive and prognostic markers. Formalin-fixed paraffin-embedded (FFPE) clinical specimens are representative of the tumor environment and are thus utilized in studies on cancer related research and biomarker discovery. Further studies on differential N-glycosylation profiling of IDC cancer tissues are necessary in order to understand the biological role of glycans in cancer and to evaluate their predictive ability. In this study, matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS)-based analyses were conducted for determining differential N-glycosylation patterns of IDC. Two different derivatization methods, namely, 2-aminobenzoic acid (2-AA) labeling and linkage-specific sialic acid esterification, were used for the analysis of N-glycans. Forty-seven 2-AA labeled and fifty ethyl esterified N-glycans were identified by MALDI-MS. In statistical analyses conducted for 2-AA-labeled N-glycans, the relative amounts of 32 N-glycans and prevalence of 15 N-glycan traits showed significant (p < 0.05) differences between cancer and normal tissues; and in such analyses for the ethyl-esterified N-glycans, the relative amounts of 27 N-glycans and prevalence of 17 N-glycan traits showed significant (p < 0.05) differences between them. It was found that mainly high mannose N-glycans, including H5N2, H6N2, and H7N2, and two fucosylated compositions (H3N3F1 and H5N5F1) showed strong discrimination between IDC and controls. In addition, compared with the controls, high mannose N-glycans were observed to be up-regulated in IDC whereas bisecting N-glycans were down-regulated.

Synthesis and Characterization of Activated Carbon from Biowaste-Peanut Shell and Application to Preconcentration/Removal of Uranium.

This study aims to synthesize and characterize an economical and ecological adsorbent with high adsorption capacity. For this purpose, the peanut shells (Pistacia vera L.) were modified chemically. After the synthesis of activated carbon (AC), the optimum conditions for enrichment steps were performed using parameters: pH and contact time for uranium in the model solutions. The measurements were carried out by inductively coupled plasma-mass spectrometry (ICP-MS). From the shapes of the BET isotherms, the AC obtained exhibits type I. The study indicated that the surface area and total pore volume of the AC were found to be 679.9 m2 g-1 and 0.31 cc g-1, respectively. The adsorption capacity was found to be 260 mg g-1. The optimum pH was found to be 6.0 for enrichment using the AC obtained by sulfuric acid as a chemical-modifier. The optimized method was applied to enrichment of U at ppb levels in the model solutions.

Calcium Fructoborate Prevents Skin Cancer Development in Balb-c Mice: Next Part, Reverse Inflammation, and Metabolic Alteration.

Metabolic alterations and inflammation are regarded as hallmarks of cancer. Glycolytic flux and intermediate accumulation lead to the production of building blocks and NADPH which is important in protecting the cell from oxidative damage. Inflammation causes the release of mediators responsible for regulating molecular mechanism affecting metabolic pathways. CaFB due to its cis-diol-rich feature may have the potential to interact with molecules taking part in cancer development. This study was aimed to investigate the effects of CaFB on metabolic alterations and inflammation in 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin cancer. For this purpose, 92 Balb-c mice were distributed into 6 groups as control, CaFB, DMBA/TPA (D-T), treatment 1 (T1), 2 (T2), and 3(T3). Apart from control and CaFB in other groups, tumors initiated with 97.5-nmol DMBA and 6.5-nmol TPA. Treatment groups received 3 mg/kg/day CaFB with DMBA (T1), with TPA (T2), and after tumor formation (T3). In the D-T group, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, 6-phosphogluconate dehydrogenase (PGD), glutathione (GSH), interleukin 6 (IL-6), (IL-1ß), tumor necrosis factor-α (TNF-α) levels increased (p < 0.001) while malondialdehyde (MDA) levels decreased (p < 0.001) compared with that in control. CaFB application ameliorated DMBA-TPA effect according to the distribution time. It is noteworthy to consider CaFB as a potential preventive agent in skin cancer development.

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.

Metabolomic profiling of liver tissues after acute administration of vardenafil in rats.

Erectile dysfunction (ED) diseases have almost affected 100 million men all over the world. Orally administered phosphodiesterase 5 (PDE 5) inhibitors are the most used pharmaceutical formulations for the treatment of ED. In this study, it is aimed to investigate the metabolomics feature of orally administered vardenafil in rats. To carry out the experimental procedure eight male Wistar albino rats were used. Their livers were gently removed and metabolomics profiles of each sample were determined by UPLC Q-TOF MS. Identification of metabolites was achieved by the METLIN database. Cluster analysis was also performed via Principle Component Analysis. Several metabolites were identified and results were evaluated by XCMS software. UPLC Q-TOF MS could be successfully applied to profile biomarkers and help us understand the molecular mechanisms of vardenafil usage. It was concluded that the level of some metabolites, responsible for the collagen synthesis and Kreb's cycle, has been statistically significant after the vardenafil administration.