Body weight was shown to be the main PK covariate of phenobarbital disposition. Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO.
Tyrosine kinase inhibitors have recently become an essential tool in management of chronic myeloid leukaemia (CML). Dasatinib, a representative of those drugs, acts by inhibiting key proteins included in CML development, predominantly Bcr-Abl and Src. Its advantage is that it shows activity in many cases where other agents bring no improvement due to resistance. Pharmacokinetics of dasatinib has specific characteristics that may play an important role in achieving sufficient exposure in patients. Therefore, the key pharmacokinetic properties are summarized in this report. For example, dasatinib absorption is significantly influenced by gastric pH and its modulation can be a source of serious interactions, as well as simultaneous administration of drugs affecting cytochrome P450.
Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination and axonal damage and resulting in a range of physical, mental or even psychiatric symptoms. Key role of oxidative stress (OS) in the pathogenesis of MS has been suggested, as indicated by the biochemical analysis of cerebrospinal fluid and blood samples, tissue homogenates, and animal models of multiple sclerosis. OS causes demyelination and neurodegeneration directly, by oxidation of lipids, proteins and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. In this review, we discuss the interrelated mechanisms of the impaired redox signaling, of which the most important are inflammation-induced production of free radicals by activated immune cells and growth factors, release of iron from myelin sheath during demyelination and mitochondrial dysfunction and consequent energy failure and impaired oxidative phosphorylation. Review also provides
an overview of the interplay between inflammation, immunity and OS in MS. Finally, this review also points out new potential targets in MS regarding attenuation of OS and inflammatory response in MS.
The interaction of severity of asphyxia and HT is associated with a clinical relevant reduced PB-CL, suggesting the potential relevance of disease characteristics beyond HT itself.
The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in a phosphate buffer solution. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of the vancomycin revealed the homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following i. p. administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution.
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