Catechol-bearing imidazolium and benzimidazolium chlorides as promising antimicrobial agents

Catechol-containing imidazolium (four) and benzimidazolium chlorides (eight) were synthesized to evaluate their antimicrobial properties. All the compounds were fully characterized using ¹H and ¹³C nuclear magnetic resonance, liquid chromatography–mass spectrometry, infrared spectroscopic methods, and elemental analyses. Antimicrobial activities of the compounds were tested against the bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, and the fungal strains Candida albicans and Candida glabrata, and promising results were achieved. The two most important benzyl-substituted benzimidazolium chlorides, 3l and 3k , showed comparable activity to vancomycin against MRSA.     

“Tau Protein Targeting Via Radioiodinated Azure A For Brain Theranostics: Radiolabeling,Molecular Docking,in vitro And in vivo Biological Evaluation”

Azure-A is one of the phenothiazines (PTZs) derivatives which for decades have been used as antipsychotic drugs due to good lipophilic characteristics which enable them to pass through the blood brain barrier (BBB), besides the important property of enabeling investigation of the pathological forms of aggregated tau protein found in the neurons of the central nervous system. Radioiodination of Azure-A was carried out via an electrophilic substitution reaction using chloramine-T as oxidizing agent. The influence of various reaction parameters and conditions on radioiodination efficiency was investigated, and a high radiochemical yield of 92.07 ± 0.9 % was obtained. An in vitro cytotoxicity study of iodinated Azure-A on three cell lines (HCT-116, human colon carcinoma cell line; Hep-G2, liver carcinoma cell line and HFB-4, normal human melanocytes) was carried out, and the data revealed that ioiodinated Azure A has no to very low toxic effect. The in vivo biodistribution study of ¹³¹I-Azure A showed a high brain uptake of 6.15 ± 0.09 % injected dose/g tissue organ at 30 minutes post-injection, and its retention in brain remained high up to 2 hours, whereas the clearance from the body appeared to proceed via the renal system. The experimental data were confirmed by the molecular docking studies to predict the effect of radioiodination on the binding affinity of the parent molecule (Azure A) to tau paired helical filaments (PHFs). Both ligands showed better binding to S2 and S3 pockets of (PHFs). Consequently, radioiodinated Azure A seems to be a good candidate as an imaging agent for taupathies such as Alzheimer's disease, chronic traumatic encephalopathy, and corticobasal degeneration. Furthermore, it could be a very potent theranostics agent for brain tumors.     

Evaluation of the antiparasitic activities of imidazol-2-ylidene–gold(I) complexes

A series of cationic gold(I)–carbene complexes with various 4,5-diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. major amastigotes and T. gondii and distinct selectivity for T. gondii cells when compared with the activity against nonmalignant Vero cells. The ferrocene derivatives 1a–c are generally more active against the L. major amastigotes and the T. gondii tachyzoites than the other tested anisyl gold complexes and the approved drugs atovaquone and amphotericin B. Compounds 1a and 1e showed the highest selectivities for L. major amastigotes. Compounds 1d and 1f showed the highest selectivities for L. major promastigotes; 1f was the most active compound against L. major promastigotes of this series of compounds. The 3,4,5-trimethoxyphenyl analog 1b also exhibited a much greater selectivity for T. b. brucei cells when compared with its activity against human HeLa cells.     

Development of anatomically and lesion contrast-guided partial volume correction: new 3D formalisms and validation in phantom and clinical studies

Annals of Nuclear Medicine - The aim of the study was to correct for partial volume effect in positron emission imaging studies which is the most influential factors using three-dimensional (3D)...     

Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Diagnostic Tool in the Assessment of Tumour Angiogenesis in Urinary Bladder Cancer

PurposeThe aim of study is to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and correlation with tumour angiogenesis in evaluation of urinary bladder cancer.Material and MethodsThe study included 81 patients with recent presumed diagnosis of bladder tumour or who came for follow up after management of histopathologically proven bladder cancer. All had DCE-MRI with time–signal intensity curve. The radiologic results then correlated with the histopathologic results using both haematoxylin and eosin stain and immuno-histochemical staining for localization and evaluation of CD34 immunoreactivity as a detector for the microvessel density (MVD) and tumour angiogenesis.ResultsSeventy-one cases were pathologically proven to be malignant: 41 cases (58%) showed type III time–signal intensity curve (descending); 22 cases (31%) showed type II (plateau); and 8 cases (11%) showed type I (ascending) curve. The sensitivity of DCE-MRI in stage T1 bladder tumour was 80%; in stage T2, it was (90.9%); and in stage T3, it was (96.9%). Overall accuracy of DCE-MRI in tumour staging was 89.5% and P = .001 (significant). Values more than the cutoff value = 76.13 MVD are cystitis with sensitivity (90%), specificity (91%), and P value is .001, which is statistically highly significant.ConclusionThere is a strong positive association between DCE-MRI (staging and washout slope of the time–signal intensity curve) with histopathologic grade, tumour stage, and MVD in bladder cancer. So, DCE-MRI can be used as reliable technique in preoperative predictions of tumour behavior and affect the planning of antiangiogenetic therapy.     

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging for Differentiation Between Parotid Neoplasms

PurposeThis study was designed to evaluate the role of multiparametric magnetic resonance imaging (MRI) for differentiation of parotid gland neoplasms.MethodsProspective study was conducted upon 52 consecutive patients (30 men, 22 women; aged 24–78 years; mean, 51 years) with parotid tumours that underwent multiparametric MRI using combined static MRI, dynamic contrast enhanced (DCE) MRI, and diffusion-weighted imaging (DWI). The static MRI parameter, time signal intensity curves (TIC) derived from DCE-MRI, and apparent diffusion coefficient (ADC) values of parotid tumours were correlated with histopathological findings.ResultsStatic MRI revealed a significant difference between both benign and malignant lesions in regards to margin definition (P < .001) and T2 hypointensity (P < .013), with a diagnostic accuracy 95% and 78.33% respectively. Study of the TIC type on DCE-MRI revealed statistically significant difference between benign and malignant lesions (P < .001) and diagnostic accuracy 96.55%. There was no statistically significant difference (P = .181) between the ADC values of benign and malignant lesions. ROC curve analysis revealed that by using ADC cut-off value of 1 × 10^?3 mm²/s had accuracy of 84.62% respectively for differentiating Warthin from malignant tumours that could be modified to higher value (94.28%) by excluding lymphoma from malignant lesions. By using cutoff value of 1.3 × 10^?3 mm²/s to differentiate pleomorphic adenoma from malignancy, ROC curve analysis had high accuracy of 97.06%.ConclusionMultiparametric MRI can be used for differentiation of malignant from benign parotid tumours and characterization of some benign parotid tumours.     

Global Trends in Aspirin Resistance‐Related Research from 1990 to 2015: A Bibliometric Analysis

Aspirin resistance can be defined as the inability of the usual dose of aspirin medication to produce its antithrombotic effect. Patients with diabetes or cardiovascular disease are at higher risk of stroke, myocardial infarction or cardiovascular death due to aspirin resistance. The aim of this bibliometric study was to identify and analyse the status and trends of aspirin resistance research production at global level through publications indexed in the Scopus database; this will shed new light on future research trends and help researchers predict dynamic direction of research. Literature search using the Scopus database was conducted to assess publications related to aspirin resistance. The selected publications included the terms related to aspirin resistance in the title, abstract or keywords. The searching was accomplished on 20 March 2016 and can be considered to include all publications up to 31 December 2015. Global cumulative publication output on aspirin resistance consists of 986 papers during 1990–2015. Among the 986 documents, 19 (1.9%) were published before 2000, 567 (57.5%) were published from 2000 to 2009 and 400 (40.6%) were published from 2010 to 2015, with peak of publications on this topic in 2008. The leading country in the field of aspirin resistance was the United States, which had the greatest counts of independent articles (165) and international collaboration articles (44). Turkey was in the second rank with 78 articles, followed by Italy (68), the UK (62) and Poland (60). The total number of citations for all documents was 26,342, and the average citations per document were 26.7. The h‐index for all aspirin resistance publications was 82. This study presents the results of the first bibliometric study (including quantitative and qualitative analysis) of scientific publications in the field of aspirin renitence at global level. Aspirin resistance‐related researches have notably increased in the last years, especially from 2000 to 2015. The United States is the most prolific country, not only in research quantity but also in quality. Furthermore, Turkey and European countries provided more research related to aspirin resistance than other regions such as the developing countries.     

Outcomes of transcutaneous nerve stimulation for migraine headaches: a systematic review and meta-analysis

Journal of Neurology - Implanted and transcutaneous nerve stimulators have shown promise as novel non-pharmacologic treatment for episodic and chronic migraines. The purpose of this study was to...