Search results for " Pharmaceutic"

The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability.

2010

The individually variable and unpredictable expression of CYP3A4 compromises therapies with 50% of contemporary drugs. Gene variants explain only a fraction of this variability.We investigated the evolution of CYP3A4 transcriptional regulation by nuclear receptors such as the xenobiotics sensors PXR and CAR.The combination of a proximal ER6 element with XREM and CLEM represents the original scheme of CYP3A regulation by nuclear receptors in placental mammals. Among human CYP3A genes, this scheme is retained only in CYP3A4, whereas non-CYP3A4 genes lost these elements to a variable extent during primate evolution. In parallel, the number of elements outside XREM and CLEM potentially responsi…

Virtual lock-and-key approach: The in silico revival of Fischer model by means of molecular descriptors

2010

Abstract In the last years the application of computational methodologies in the medicinal chemistry fields has found an amazing development. All the efforts were focused on the searching of new leads featuring a close affinity on a specific biological target. Thus, different molecular modeling approaches in simulation of molecular behavior for a specific biological target were employed. In spite of the increasing reliability of computational methodologies, not always the designed lead, once synthesized and screened, are suitable for the chosen biological target. To give another chance to these compounds, this work tries to resume the old concept of Fischer lock-and-key model. The same can …

Influence of PVP/VA copolymer composition on drug–polymer solubility

2015

In this study, the influence of copolymer composition on drug-polymer solubility was investigated. The solubility of the model drug celecoxib (CCX) in various polyvinylpyrrolidone/vinyl acetate (PVP/VA) copolymer compositions (70/30, 60/40, 50/50 and 30/70 w/w) and the pure homopolymers polyvinylpyrrolidone (PVP) and polyvinyl acetate (PVA) was predicted at 25 °C using a thermal analysis method based on the recrystallization of a supersaturated amorphous dispersion (recrystallization method). These solubilities were compared with a prediction based on the solubility of CCX in the liquid monomeric precursors of PVP/VA, N-vinylpyrrolidone (NVP) and vinyl acetate (VA), using the Flory-Huggins …

Ru(bpy)2Cl2: A catalyst able to shift the course of the photorearrangement in the Boulton-Katritzky reaction

2015

The Boulton-Katritzky reaction represents one of the most popular and efficient strategies used to realize azole-into-azole conversions. For example, under different experimental conditions, it allows the rearrangement of Z-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazoles (1) into 2-aryl-4-benzoylamino-5-phenyl-2H-1,2,3-triazoles (2) in very high yields. Moreover, we have recently realized this conversion also by UV-photostimulation. Now we have enlarged the scope of the reaction irradiating with visible or UV light an acetonitrile solution of some Z-arylhydrazones (1a-e) in the presence of catalytic amounts of Ru(bpY)(2)Cl-2. We have observed the unexpected formation of the 1-aryl-5-…

2015

Transporters of the ATP-binding cassette (ABC) family such as MDR1 play a pivotal role in persistence of brain homeostasis by contributing to the strict permeability properties of the blood–brain barrier. This barrier on one hand compromises treatment of central nervous system diseases by restricting access of drugs; on the other hand, an impaired or altered function of barrier building cells has been described in neurological disorders. The latter might contribute to increased vulnerability of the brain under pathological conditions or even enforce pathogenesis. Here, we present a novel approach for a systematic examination of drug impact on Mdr1 gene expression by establishing a dual repo…

New Hepatocyte In Vitro Systems for Drug Metabolism: Metabolic Capacity and Recommendations for Application in Basic Research and Drug Development, S…

2003

Primary hepatocytes represent a well-accepted in vitro cell culture system for studies of drug metabolism, enzyme induction, transplantation, viral hepatitis, and hepatocyte regeneration. Recently, a multicentric research program has been initiated to optimize and standardize new in vitro systems with hepatocytes. In this article, we discuss five of these in vitro systems: hepatocytes in suspension, perifusion culture systems, liver slices, co-culture systems of hepatocytes with intestinal bacteria, and 96-well plate bioreactors. From a technical point of view, freshly isolated or cryopreserved hepatocytes in suspension represent a readily available and easy-to-handle in vitro system that c…

Responsabilità per danno da farmaco tra gestione del rischio e ruolo delle informazioni

2022

Il contributo, dopo aver analizzato le conseguenze dell’inclusione della responsabilità per i danni da prodotti farmaceutici all’interno del regime della responsabilità del produttore da prodotto difettoso ovvero del paradigma di responsabilità da attività pericolose, indaga criticamente le più recenti decisioni sulla responsabilità del produttore farmaceutico, soffermandosi sulla valenza assunta dalle informazioni. In un contesto in cui le esigenze di protezione della persona richiedono un rafforzamento della tutela del consumatore, sarebbe opportuno, anche alla luce del principio di precauzione, tenere in conto il profilo della gestione del rischio e individuare nuove prospettive di tutel…

Acyclovir Delivery Matrices Based on Poly(Ethylene Glycol)/Chitosan Semi-Interpenetrating Networks

2007

Abstract Chitosan matrix systems have been studied as potential vehicles for the prolonged release of acyclovir (ACV). The influence of chitosan concentration (from 0.83% to 1.67%) on viscoelastic properties of formulations with and without glyoxal was analyzed. For chitosan‐poly(ethylene glycol) 400 formulations loss modulus ( G ″) are greater than storage modulus ( G ′). This corresponds to the characteristic behavior of nonstructured systems. When glyoxal was added to the chitosan‐poly(ethylene glycol) 400 formulations, gelled matrix was obtained (i.e., G ′ is higher than G ″), except for the lowest chitosan concentration. ACV release rates for the both types of systems, with and without…

Monitoring the rate of hospitalization before rotavirus immunization in Italy utilizing ICD9-CM regional databases

2009

BACKGROUND: Recently, two Rotavirus (RV) vaccines were licensed in Italy, rendering RV illness a vaccine preventable disease. To assess the RV hospitalization rate in Italy, a study focused on the Regional hospital discharge forms (HDD) databases was carried out. RESULTS: Regional HDD databases from Piemonte, Veneto, Friuli-Venezia-Giulia and Marche were analyzed. A total of 434,335 hospitalizations were counted in the study timeframe and 13,234 VE diagnoses (3% of hospitalizations) were collected. A total of 8546 RVE cases (2% of hospitalizations, 64% of all VE) were observed, of which 1.2% were primary diagnoses (PD) and 0.8% secondary diagnosis (SD). The RVE hospitalization peak (4.9%) w…

The Deep-Sea Natural Products, Biogenic Polyphosphate (Bio-PolyP) and Biogenic Silica (Bio-Silica), as Biomimetic Scaffolds for Bone Tissue Engineeri…

2013

Bone defects in human, caused by fractures/nonunions or trauma, gain increasing impact and have become a medical challenge in the present-day aging population. Frequently, those fractures require surgical intervention which ideally relies on autografts or suboptimally on allografts. Therefore, it is pressing and likewise challenging to develop bone substitution materials to heal bone defects. During the differentiation of osteoblasts from their mesenchymal progenitor/stem cells and of osteoclasts from their hemopoietic precursor cells, a lineage-specific release of growth factors and a trans-lineage homeostatic cross-talk via signaling molecules take place. Hence, the major hurdle is to fab…