Current Issue : January - March Volume : 2016 Issue Number : 1 Articles : 5 Articles
It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction.\nDespite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive,\nand regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become\nchronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead\nto compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression\nfrom a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve\nthis, various animal models in combination with an ââ?¬Å?omicsââ?¬Â toolbox can be used. These approaches will ultimately lead to the\nidentification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future....
Experimental animal models improve our understanding of technical problems in peritoneal dialysis PD, and such studies\ncontribute to solving crucial clinical problems. We established an acute and chronic PD model in non uremic and uremic rats.\nWe observed that kinetics of PD in rats change as the animals are aging, and this effect is due not only to an increasing peritoneal\nsurface area, but also to changes in the permeability of the peritoneum. Changes of the peritoneal permeability seen during chronic\nPD in rats are comparable to results obtained in humans treated with PD. Effluent dialysate can be drained repeatedly to measure\nconcentration of various bioactive molecules and to correlate the results with the peritoneal permeability. Additionally we can study\nin in vitro conditions properties of the effluent dialysate on cultured peritoneal mesothelial cells or fibroblasts.We can evaluate acute\nand chronic effect of various additives to the dialysis fluid on function and permeability of the peritoneum. Results from such study\nare even more relevant to the clinical scenario when experiments are performed in uremic rats. Our experimental animal PD model\nnot only helps to understand the pathophysiology of PD but also can be used for testing biocompatibility of new PD fluids....
Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce\nclinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the\npresence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates\nimmunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory\ndiseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was\ninduced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.)\nand were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-...
We describe the multigram synthesis and in vivo efficacy studies of\na donepezilââ?¬â??huprine hybrid that has been found to display a promising in vitro multitarget\nprofile of interest for the treatment of Alzheimerââ?¬â?¢s disease (AD). Its synthesis features as\nthe key step a novel multigram preparative chromatographic resolution of intermediate\nracemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human AÃ?²42, here used as\nsimplified animal models of AD, led to a significant protection from the toxicity induced\nby AÃ?²42. However, this protective effect was not accompanied, in CL2006 worms, by a\nreduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a\nwell-established animal model of AD, improved short-term memory, but did not alter brain\nlevels of AÃ?² peptides nor cortical and hippocampal amyloid plaque load. Despite the clear\nprotective and cognitive effects of AVCRI104P4, the lack of AÃ?² lowering effect in vivo\nmight be related to its lower in vitro potency toward AÃ?² aggregation and formation as\ncompared with its higher anticholinesterase activities. Further lead optimization in this\nseries should thus focus on improving the anti-amyloid/anticholinesterase activity ratio....
To precisely and faithfully perform cell-based drug chemosensitivity assays, a well-defined and biologically relevant culture\ncondition is required. For the former, a perfusion microbioreactor system capable of providing a stable culture condition was\nadopted. For the latter, however, little is known about the impact of culture models on the physiology and chemosensitivity\nassay results of primary oral cavity cancer cells. To address the issues, experiments were performed. Results showed that minor\nenvironmental pH change could significantly affect the metabolic activity of cells, demonstrating the importance of stable culture\ncondition for such assays. Moreover, the culture models could also significantly influence the metabolic activity and proliferation\nof cells. Furthermore, the choice of culture models might lead to different outcomes of chemosensitivity assays. Compared with the\nsimilar test based on tumor-level assays, the spheroid model could overestimate the drug resistance of cells to cisplatin, whereas the\n2D and 3D culture models might overestimate the chemosensitivity of cells to such anticancer drug. In this study, the 3D culture\nmodels with same cell density as that in tumor samples showed comparable chemosensitivity assay results as the tumor-level assays.\nOverall, this study has provided some fundamental information for establishing a precise and faithful drug chemosensitivity assay....
Loading....