Search results for "Wistar"
showing 10 items of 1094 documents
Dissolution and dissolution/permeation experiments for predicting systemic exposure following oral administration of the BCS class II drug clarithrom…
2017
In order to save time and resources in early drug development, in vitro methods that correctly predict the formulation effect on oral drug absorption are necessary. The aim of this study was to 1) evaluate various BCS class II drug formulations with in vitro methods and in vivo in order to 2) determine which in vitro method best correlates with the in vivo results. Clarithromycin served as model compound in formulations with different particle sizes and content of excipients. The performed in vitro experiments were dissolution and dissolution/permeation experiments across two types of membrane, Caco-2 cells and excised rat intestinal sheets. The in vivo study was performed in rats. The oral…
Noradrenaline release from permeabilized synaptosomes is inhibited by the light chain of tetanus toxin
1992
AbstractNoradrenaline release from rat brain cortical synaptosomes permeabilized with streptolysin O can be triggered by μM concentrations of free Ca2+. This process was inhibited within minutes by tetanus toxin and its isolated light chain, but not by its heavy chain. The data demonstrate that the effect of tetanus toxin on NA release from purified synaptosomes is caused by the intraterminal action of its light chain.
Mechanistic basis for unexpected bioavailability enhancement of polyelectrolyte complexes incorporating BCS class III drugs and carrageenans
2013
The objective of this study was to investigate the potential of λ-carrageenan to work as an absorption modifying excipient in combination with formulations of BCS class 3 substances. Trospium chloride was used as a model BCS class 3 substance. Polyelectrolyte complexes of trospium and λ-carrageenan were produced by layer-by-layer complexation. A λ-carrageenan-containing formulation was administered either in capsules size 9 to rats by gavage or directly into ligated intestinal loops of rats. Exceptionally strong variations were observed in the plasma concentrations of the rats that received λ-carrageenan compared to the control group, but enhanced plasma concentrations were observed only in…
Redox state alteration modulates astrocyte glucuronidation.
2004
We have investigated the effects of mild oxidative conditions on drug-metabolizing enzyme activity in rat cultured astrocytes. These experimental conditions promoting an oxidative environment were obtained by short exposure to a low concentration of menadione (5 microM) for a short duration (15 min). This resulted in the rapid and transient production of reactive oxygen species (+130%), associated with a decrease in GSH cellular content (-24%), and an increase in total protein oxidation (+26%), but promoted neither PGE(2) nor NO production. This treatment induced a rapid and persistent decrease in astrocyte glucuronidation activities, which was totally prevented by N-acetyl-l-cysteine. Thes…
Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment.
2006
Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferatio…
Unique pharmacology of KAR-2, a potential anti-cancer agent: absorption modelling and selective mitotic spindle targeting.
2008
Abstract Bis-indols are a large group of the anti-cancer agents, which effectively arrest the uncontrolled division of the cancerous cells. Their use in clinical chemotherapy is still limited because of: (i) the non-specific targeting of the mitotic cells; (ii) low bioavailability of the drugs. KAR-2 has been identified as a tubulin binding agent which displays significantly lower cytotoxicity but favourable anti-cancer potency than its mother molecule, vinblastine. The objective of this paper, on one hand, was to show that the human intestinal epithelial Caco-2 cells, used for pharmacokinetic studies display distinct sensitivity against KAR-2 and vinblastine due to their distinct targeting…
Cell type-specific circuits of cortical layer IV spiny neurons
2003
Sensory signal processing in cortical layer IV involves two major morphological classes of excitatory neurons: spiny stellate and pyramidal cells. It is essentially unknown how these two cell types are integrated into intracortical networks and whether they play different roles in cortical signal processing. We mapped their cell-specific intracortical afferents in rat somatosensory cortex through a combination of whole-cell patch-clamp recordings and caged glutamate photolysis. Spiny stellate cells received monosynaptic excitation and inhibition originating almost exclusively from neurons located within the same barrel. Pyramidal cells, by contrast, displayed additional excitatory inputs fr…
Cellular localization of mGluR3 and mGluR5 mRNAs in normal and injured rat brain
2007
Abstract In order to understand the role of metabotropic glutamate receptors (mGluRs) in the brain, it is important to know how the mGluRs are differentially expressed among the different cell types. At present, the cellular expression of mGluR3 and mGluR5 has been mostly studied in terms of proteins with observations suggesting the expression of both mGluR3 and mGluR5 in neuronal and in glial cells. In order to verify the brain cell type-expressing mGluR3 and mGluR5 mRNAs, both in normal and injured brain, we performed a double labeling analysis, by in situ hybridization for mGluR3 or mGluR5 mRNA and immunohistochemistry for specific cellular markers. This approach allowed us to find mGluR…
Effects of human recombinant interleukins on stimulation-evoked noradrenaline overflow from the rat perfused spleen
1994
Experiments were carried out in the isolated spleen of the rat to study in a lymphoid organ the influence of interleukins (ILs) on noradrenaline release. Spleens were perfused with Tyrode's solution and the overflow of endogenous noradrenaline was determined by HPLC with electrochemical detection. Perivascular electrical stimulation (4 or 10 Hz, 20-28 mA, 2 min) caused an increase in noradrenaline overflow and in perfusion pressure, both of which were markedly reduced by perfusion with Ca(2+)-free solution, abolished by tetrodotoxin, unaffected by hexamethonium, and subject to alpha 2-adrenoceptor- and muscarinic receptor-mediated modulation as shown by the effects of rauwolscine and methac…
Characterization of oscillatory changes in hippocampus and amygdala after deep brain stimulation of the infralimbic prefrontal cortex
2016
Deep brain stimulation (DBS) is a new investigational therapy that has generated positive results in refractory depression. Although the neurochemical and behavioral effects of DBS have been examined, less attention has been paid to the influence of DBS on the network dynamics between different brain areas, which could contribute to its therapeutic effects. Herein, we set out to identify the effects of 1 h DBS in the infralimbic cortex (IL) on the oscillatory network dynamics between hippocampus and basolateral amygdala (BLA), two regions implicated in depression and its treatment. Urethane-anesthetized rats with bilaterally implanted electrodes in the IL were exposed to 1 h constant stimul…