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Thyrotropin-releasing hormone (TRH) is engaged in the modulation of the hypothalamo-neurohypophysial system activity. Effects of repeated intravenously injections of TRH in a dose of 100 ng/100 g b.w. on vasopressin (VP) and oxytocin (OT) biosynthesis and release from the hypothalamo-neurohypophysial system was investigated in rats in different age (1-, 3- or 7-months of the life). To estimate the biosynthesis rate of both neurohormones the colchicine procedure was used (the dose of 5 µg/5 µl icv 20 hours before the decapitation). It has been observed that vasopressin synthesis in the hypothalamus increased gradually with maturation of rats, while OT biosynthesis decreased in the same animals. Hypothalamic biosynthesis rate of VP and OT is most effective in youngest rats and declines during the adolescence of animals. Thyrotropin-releasing hormone directly affects VP-ergic and OT-ergic hypothalamic neurons activity and both neurohormones biosynthesis process. This effect, however, is opposed: TRH acts as a stimulator of vasopressin biosynthesis most of all in young male rats and as an inhibitor for oxytocin biosynthesis especially in mature animals.
The aim of this study was to determine the pharmacokinetics of tramadol and its main metabolites after IV and IM injections. The pharmacokinetic cross-over study was carried out on 6 healthy male beagle dogs. Tramadol was administered by intravenous (IV) and intramuscular (IM) injection at 4 mg/kg. Tramadol and its main metabolites O-desmethyl-tramadol (M1), N-,N-didesmethyl-tramadol (M2) and N-,O-didesmethyl-tramadol (M5) concentrations were measured in plasma samples by a HPLC coupled with fluorimetric detection; pharmacokinetic evaluations were carried out with a compartmental and non-compartmental model for tramadol and its metabolites, respectively. The bioavailability of the drug, ranging between 84-102% (mean 92%), was within the generally accepted values for a positive bioequivalence decision of (80-125%). After the IM injection the mean plasma drug concentration peak was reached after a Tmax of 0.34 h with a Cmax of 2.52 μg/mL. No therapeutic relevant differences were observed between IM and IV administration. The minimal effective plasma concentration was reached after a few minutes and maintained for about 6-7 h in both administrations. M1 plasma concentration was low and the amounts of the other metabolites produced were analogous in both routes of administration. In conclusion, tramadol was rapidly and almost completely absorbed after IM administration and its systemic availability was equivalent to the IV injection. The different onset time and duration of action observed were very small and probably therapeutically irrelevant. The IM injection is a useful alternative to IV injection in the dog.
Human adipose-derived stem cells (huADSC) were generated from fat tissue of a 65-year-old male donor. Flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) analyses indicated that the huADSC express neural cell proteins (MAP2, GFAP, nestin and β-III tubulin), neurotrophic growth factors (BDNF and GDNF), and the chemotactic factor CXCR4 and its corresponding ligand CXCL12. In addition, huADSC expressed the characteristic mesenchymal stem cell (MSC) markers CD29, CD44, CD73, CD90, CD105 and HLA class I. The huADSC were employed, via a right femoral vein injection, to treat rats inflicted with experimental intracerebral hemorrhage (ICH). Behavioral measurement on the experimental animals, seven days after the huADSC therapy, showed a significant functional improvement in the rats with stem cell therapy in comparison with rats of the control group without the stem cell therapy. The injected huADSC were detectable in the brains of the huADSC treated rats as determined by histochemistry analysis, suggesting a role of the infused huADSC in facilitating functional recovery of the experimental animals with ICH induced stroke.
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