Search results for "Models"
showing 10 items of 8211 documents
Comparison between iMSD and 2D-pCF analysis for molecular motion studies on in vivo cells: The case of the epidermal growth factor receptor.
2018
Image correlation analysis has evolved to become a valuable method of analysis of the diffusional motion of molecules in every points of a live cell. Here we compare the iMSD and the 2D-pCF approaches that provide complementary information. The iMSD method provides the law of diffusion and it requires spatial averaging over a small region of the cell. The 2D-pCF does not require spatial averaging and it gives information about obstacles for diffusion at pixel resolution. We show the analysis of the same set of data by the two methods to emphasize that both methods could be needed to have a comprehensive understanding of the molecular diffusional flow in a live cell.
Traits and risk factors of post-disaster infectious disease outbreaks: a systematic review.
2021
AbstractInfectious disease outbreaks are increasingly recognised as events that exacerbate impacts or prolong recovery following disasters. Yet, our understanding of the frequency, geography, characteristics and risk factors of post-disaster disease outbreaks globally is lacking. This limits the extent to which disease outbreak risks can be prepared for, monitored and responded to following disasters. Here, we conducted a global systematic review of post-disaster outbreaks and found that outbreaks linked to conflicts and hydrological events were most frequently reported, and most often caused by bacterial and water-borne agents. Lack of adequate WASH facilities and poor housing were commonl…
The therapeutic potential of inorganic polyphosphate: A versatile physiological polymer to control coronavirus disease (COVID-19).
2021
Rationale: The pandemic caused by the novel coronavirus SARS-CoV-2 is advancing rapidly. In particular, the number of severe courses of the disease is still dramatically high. An efficient drug therapy that helps to improve significantly the fatal combination of damages in the airway epithelia, in the extensive pulmonary microvascularization and finally multiorgan failure, is missing. The physiological, inorganic polymer, polyphosphate (polyP) is a molecule which could prevent the initial phase of the virus life cycle, the attachment of the virus to the target cells, and improve the epithelial integrity as well as the mucus barrier. Results: Surprisingly, polyP matches perfectly with the ca…
Targeted delivery of Cyclosporine A by polymeric nanocarriers improves the therapy of inflammatory bowel disease in a relevant mouse model
2017
The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects. As had already been demonstrated in previous studies, nano- to micrometer-sized drug particles will accumulate at inflamed mucosal areas, providing a platform for such purposes. …
Abacavir Induces Arterial Thrombosis in a Murine Model.
2018
Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombu…
Shikonin derivatives for cancer prevention and therapy.
2019
Abstract Phytochemicals gained considerable interest during the past years as source to develop new treatment options for chemoprevention and cancer therapy. Motivated by the fact that a majority of established anticancer drugs are derived in one way or another from natural resources, we focused on shikonin, a naphthoquinone with high potentials to be further developed as preventive or therapeutic drug to fight cancer. Shikonin is the major chemical component of Lithospermum erythrorhizon (Purple Cromwell) roots. Traditionally, the root extract has been applied to cure dermatitis, burns, and wounds. Over the past three decades, the anti-inflammatory and anticancer effects of root extracts, …
A lipidomic cell-based assay for studying drug-induced phospholipidosis and steatosis
2017
Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS-based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC-MS lipid profiling of HepG2 cells is proposed as an in vitro assay to study and anticipate phospholipidosis and steatosis. Cells with and without pre-incubation with a mixture of free fatty acids (FFA) (i.e., oleic and palmitic) were exposed to a set of well-known steatogenic and phospholipidogenic compounds. The use of FFA pre-loading accelerated the accumulation of phospholipids thus leading to a better discrimination of phospholipidosis, and magnified the lipid…
Partial resistance to homologous challenge infections of the digenean Echinostoma caproni in ICR mice
2015
AbstractIn the present paper, we analyse the effect of a primary infection of ICR mice with Echinostoma caproni (Trematoda: Echinostomatidae) on the generation of resistance against homologous challenge infections. In ICR mice, E. caproni induces chronic infections concomitantly with strong responses characterized by the development of T-helper 1 (Th1)-type local immune responses with elevated levels of local interferon-gamma (IFN-γ) and inflammatory and antibody responses. Here, the effect of the response generated against a primary infection with E. caproni in the generation of resistance against subsequent homologous infections was analysed. For this purpose, ICR mice were challenged wit…
Sema3a plays a role in the pathogenesis of CHARGE syndrome
2018
CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7. Chd7 regulates the expression of Sema3a, which also contributes to the pathogenesis of Kallmann syndrome, a heterogeneous condition with the typical features hypogonadotropic hypogonadism and an impaired sense of smell. Both features are common in CHARGE syndrome suggesting that SEMA3A may provide a genetic link between these syndromes. Indeed, we find evidence that SEMA3A plays a role in the pathogenesis of CHARGE syndrome. First, Chd7 is enriched at the Sema3a promotor in neural crest cells and loss of function of Chd7 inhibits Sema3a expression…
Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition
2017
Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents. In our tests, we used a turkey fetus model to investigate time dependent tissue concentrations in pharmacological and toxicological rele…