PubMed · 13105105
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F NATELLIS. 1953. [Spiropulsometer for experimental surgery].. https://pubmed.ncbi.nlm.nih.gov/13105105/
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A method coupled with microdialysis technique and liquid chromatography was applied in the continuous and concurrent in vivo monitoring of extracellular hesperidin in the blood and bile of anaesthetized rats. Hesperidin was intravenously administered via the femoral vein. Sampling was achieved using two microdialysis probes, which were implanted into the jugular vein and into the bile duct. Dialysates of blood and bile were both directly injected onto the liquid chromatographic system, so no further clean-up procedures were required. Separation was performed using a reversed phase ODS-2 microbore column 150 mm x 1 mm i.d., particle size 5 microm with mobile phase of acetonitrile-0.1M ammonium acetate (30:70, v/v) at flow-rate of 0.05 ml/min. The UV detection for hesperidin was set at a wavelength of 283 nm. This method was used to determine the pharmacokinetics of hesperidin and its interaction in the presence of cyclosporin A, which is a P-glycoprotein modulator. The results indicate that the curve of area under the concentration versus time (AUC) for hesperidin in bile was significantly greater than that for hesperidin in blood at the dose of 30 mg/kg. The blood-to-bile distribution ratio (k = AUC(bile)/AUC(blood)) was 8.9 +/- 2.5 for hesperidin at 30 mg/kg. Following cyclosporin A treatment, the distribution ratio was reduced to 3.2 +/- 0.6. In conclusion, hesperidin goes through hepatobiliary elimination against the concentration gradient from blood to bile, and this hepatobiliary excretion of hesperidin may be regulated by the P-glycoprotein.
In the present study, we investigated the effects of cholinomimetic drugs on the urodynamic characteristics in anesthetized guinea pigs. 8-[3-[1-[(3-fluorophenyl)methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802), a novel acetylcholinesterase inhibitor, (0.003-0.03 mg/kg, i.v.) increased the voided volume and the maximum flow rate without affecting either the intravesical pressure or the bladder compliance. Distigmine (0.03-0.3 mg/kg, i.v.) and neostigmine (0.01-0.1 mg/kg, i.v.), both carbamate acetylcholinesterase inhibitors, while not increasing the maximum flow rate, increased the intravesical pressure at the maximum flow rate. They also decreased the bladder compliance. Bethanechol (0.1-1 mg/kg, i.v.), a muscarinic receptor agonist, decreased the voided volume and the bladder compliance but did not affect the maximum flow rate. TAK-802 did not affect the intraurethral pressure at doses of up to 0.03 mg/kg in anesthetized guinea pigs. Distigmine increased the intraurethral pressure when administered at the dose of 0.3 mg/kg, and the effect was completely abolished by pretreatment with d-tubocurarine. These results suggest that TAK-802 reinforces the bladder-voiding functions by increasing the bladder contractility without decreasing the storage function. On the other hand, carbamate acetylcholinesterase inhibitors not only deteriorate the voiding function by inducing contraction of the external urethral sphincter muscle, resulting in increasing the urethral resistance, but also cause deterioration of the storage function. Bethanechol obviously decreased the bladder capacity, possibly due to a direct contractile effect on the detrusor smooth muscle. TAK-802 may therefore be a more useful drug than either carbamate acetylcholinesterase inhibitors or muscarinic receptor agonists in the treatment of voiding dysfunction associated with impaired detrusor contractility.
To establish a new model of conditioned enhancement of antibody production, electroacupuncture was served as the conditioned stimulus (CS) and an injection of a protein antigen ovalbumin as the unconditioned stimulus (UCS). After a CS/UCS pairing was made, re-exposure of animals to the CS alone resulted in significant conditioned enhancement of anti-ovalbumin antibody production. Even in deep sleep induced by anesthesia, the animals can associate a single CS with UCS and an antibody response can be elicited upon subsequent re-exposure to CS in the absence of exogenous antigen. No effect of electroacupuncture on anti-ovalbumin antibody production was found.