Search results for "Mace"

Imaging biomarkers of behavioral impairments: A pilot micro-positron emission tomographic study in a rat electrical post-status epilepticus model.

2018

Objective In patients with epilepsy, psychiatric comorbidities can significantly affect the disease course and quality of life. Detecting and recognizing these comorbidities is central in determining an optimal treatment plan. One promising tool in detecting biomarkers for psychiatric comorbidities in epilepsy is positron emission tomography (PET). Methods Results Behavioral and biochemical variables were cross-correlated with the results from two mu PET scans using the tracers [F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG) and 2 '-methoxyphenyl-(N-2 '-pyridinyl)-p-F-18-fluoro-benzamidoethylpiperazine ([F-18]MPPF) to explore potential biomarkers for neurobehavioral comorbidities in an electrica…

Final analysis of the phase III multicentric Italian study Short-HER: 9 weeks vs 1 year adjuvant trastuzumab for HER2+ early breast cancer

2017

2017

Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of …

A Comprehensive Spectroscopic Analysis of the Ibuprofen Binding with Human Serum Albumin, Part I

2020

Human serum albumin (HSA) plays a fundamental role in the human body. It takes part in the transport of exogenic and endogenic substances, especially drugs. Ibuprofen (IBU) is one of the most commonly used non-steroidal anti-inflammatory drugs, used for pain relief, fever relief, and for anti-inflammatory purposes. The binding of ligands with HSA is a significant factor which determines the toxicity and the therapeutic dosages of these substances. The aim of this study was to compare the degree of ibuprofen binding with human serum albumin at various temperatures and protein solution pH values. In order to evaluate conformational changes in HSA caused by interaction with ibuprofen, spectrop…

New insights in primary ciliary dyskinesia

2017

Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disease with an estimated prevalence of 1:20.000 births. It is characterized by abnormal motility of cilia, leading to impaired mucociliary clearance, and subsequent infection and chronic inflammation of the airways. PCD also affects spermatozoa and cilia in the Fallopian tubes, contributing to fertility issues; dyskinesia of embryonic nodal cilia causes a random distribution of the organs. Areas covered: An overview of the history, genetics, clinical manifestations in children and adults, diagnostic tests, treatments, and prognosis are reviewed. We also discuss current research and future prospects of PCD. Expert opinion: As …

Cystic fibrosis treatment: targeting the basic defect

2017

ABSTRACTIntroduction: Cystic Fibrosis (CF) is a disease caused by different class mutations in the CF transmembrane conductance regulator (CFTR) gene. It can therefore benefit from a personalized medicine approach based on the individual genotype of each patient.Areas covered: This review provides a detailed overview of the current major development of new CF treatments that target the basic CF defect. The review summarizes gene therapy, mRNA repair strategies, read-through agents, and CFTR-modulators (potentiators, correctors, stabilizers, amplifiers and different combination therapies).Expert opinion: We are currently perhaps at the most exciting stage in the history of CF, with the poten…

Drug Distribution to Retinal Pigment Epithelium: Studies on Melanin Binding, Cellular Kinetics, and Single Photon Emission Computed Tomography/Comput…

2016

Melanin binding is known to affect the distribution and elimination of ocular drugs. The purpose of this study was to evaluate if the extent of drug uptake to primary retinal pigment epithelial (RPE) cells could be estimated based on in vitro binding studies with isolated melanin and evaluate the suitability of single photon emission computed tomography/computed tomography (SPECT/CT) in studying pigment binding in vivo with pigmented and albino rats. Binding of five compounds, basic molecules timolol, chloroquine, and nadolol and acidic molecules methotrexate and 5(6)-carboxy-2',7'-dichlorofluorescein (CDCF), was studied using isolated melanin from porcine choroid-RPE at pH 5.0 and 7.4. The…

Pharmacogenomics of Scopoletin in Tumor Cells

2016

Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS onc…

Cytotoxicity and mode of action of a naturally occurring naphthoquinone, 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone towards multi-factorial dr…

2017

Abstract Introduction Malignacies are still a major public concern worldwide and despite the intensive search of new chemotherapeutic agents, treatment still remains a challenging issue. The present study was designed to evaluate the cytotoxicity of 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone (AMNQ) isolated from the bark of Milletia versicolor towards a panel of drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of AMNQ against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyze…

Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds

2018

Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines. Artesunic acid (ARTA), a drug for malaria treatment, also exerts cytotoxic activity towards cancer cells. Multidrug resistance often results fro…