Search results for " TOXICOLOGY AND PHARMACEUTICS"
showing 10 items of 461 documents
A systematic review and combined analysis of therapeutic drug monitoring studies for longacting risperidone
2017
Introduction: This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value…
The Understanding of the Metazoan Skeletal System, Based on the Initial Discoveries with Siliceous and Calcareous Sponges
2017
Initiated by studies on the mechanism of formation of the skeletons of the evolutionary oldest still extant multicellular animals, the sponges (phylum Porifera) have provided new insights into the mechanism of formation of the Ca-phosphate/hydroxyapatite skeleton of vertebrate bone. Studies on the formation of the biomineral skeleton of sponges revealed that both the formation of the inorganic siliceous skeletons (sponges of the class of Hexactinellida and Demospongiae) and of the calcareous skeletons (class of Calcarea) is mediated by enzymes (silicatein: polymerization of biosilica; and carbonic anhydrase: deposition of Ca-carbonate). Detailed studies of the initial mineralization steps i…
The complex modulation of lysosomal degradation pathways by cannabinoid receptors 1 and 2
2015
The two main receptors of the endocannabinoid system, cannabinoid receptors 1 (CB1R) and 2 (CB2R), were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors. CB1R and CB2R activities influence signal cascades, which are known to play a role in the regulation of the cellular "self-digestion" process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the auto…
Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac f…
2021
Abstract Aims Doxorubicin (DOX) is an important drug for the treatment of various tumor entities. However, the occurrence of heart failure limits its application. This study investigated differential gene expression profiles in the left and right ventricles of DOX treated mice with either preserved or impaired myocardial function. We provide new mechanistic insights into the pathophysiology of DOX-induced heart failure and have discovered pathways that counteract DOX-induced cardiotoxicity. Main methods We used in total 48 male mice and applied a chronic low dose DOX administration (5 mg/kg per injection, in total 20 mg/kg over 4 weeks) to induce heart failure. Echocardiographic parameters …
Physicochemical stability of carmustine-containing medicinal products after reconstitution and after dilution to ready-to-administer infusion solutio…
2020
Introduction The aim of this study was to determine and compare the physicochemical stability of two carmustine-containing medicinal products licensed and marketed in Europe as Carmustin Obvius (Medac GmbH) and Carmubris (Tillomed Pharma GmbH). Reconstituted stock solutions and diluted ready-to-administer infusion solutions of the two products were investigated. Methods Reconstituted carmustine stock solutions (3.3 mg/mL) and ready-to-administer infusion solutions (0.2 mg/mL, 1.0 mg/mL) prepared in prefilled 5% glucose injection solution PP/PE bags were stored at 22°C or 2–8°C over a maximum period of 66 hours protected from light. Samples were taken immediately after reconstitution or dilu…
Uridine enhances the cytotoxic effect of D-glucosamine in rat C6 glioma cells.
1986
This paper studies the influence of uridine on the effects exerted by D-glucosamine in rat C6 glioma cells. 2 mM uridine increased markedly both the cytotoxic effect of the aminosugar and the inhibition of thymidine incorporation into acid-insoluble fraction. Furthermore the complete resumption of the capacity to incorporate either 3H-thymidine or 3H-mannose which was observed after the removal of the aminosugar, was impeded when the cells were treated contemporaneously with D-glucosamine and uridine. An exposure for 4 hr to 20 mM glucosamine alone enhanced about 15-fold the cellular pool of UDP-N-acetylhexosamines; the addition of 2 mM uridine intensified the expansion of this pool, which …
Effect of L-Histidine on the Survival of a T-Strain of Mycoplasma
1975
The addition of L-histidine to the growth medium prolongs the stationary phase and the survival of a T-strain of mycoplasma. Results of an experiment performed with 14 C-labeled urea demonstrate that the action of L-histidine is based on the retardation of the rise of pH.
An organogold compound as potential antimicrobial agent against drug resistant bacteria: Initial mechanistic insights
2021
Abstract The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal‐based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram‐positive bacteria, including multi‐drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number …
Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.
2009
This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different t…
Halogenated derivatives of boldine with high selectivity for alpha1A-adrenoceptors in rat cerebral cortex.
1999
The selectivity of 3-nitrosoboldine and different halogenated derivatives of boldine (3-bromoboldine, 3,8-dibromoboldine and 3-chloroboldine) for alpha1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. In the competition experiments [3H]-prazosin binding was inhibited completely by all the compounds tested. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components. The relative order of affinity and selectivity for alpha1A-adrenoceptors was 3-bromoboldine = 3,8-dibromoboldine = 3-chloroboldineboldine3-nitrosoboldine. The competition curves for 3-bromoboldine remained shallow and biph…