[Patient-controlled postoperative analgesia in obstetrics and gynaecology].

A prospective study researches features of patient-controlled epidural analgesia (PCEA) in 42 women after cesarean section, mid- and high-traumatic gynaecological surgery. It was found out that the quality of while using the PCEA is significantly better than while using a traditional parenteral infusion of analgesics. Use of PCEA favours the circulatory and breathing systems functioning. Compared to continuous epidural infusion of analgesics and anaesthetics, use of PCME returns the expenses better due to less consumption of the drugs up to 35% during the first 24 hours after the surgery. This method is suitable for continuous estimation of the pain therapy.

[Experimental investigations of the analgesic activity of fentanyl and the non-opiodal agents -clonidine and isradipine, and protease inhibitors].

The analgesic activity of clonidine, isradipine, antagosane (aprotinine), transamine, and their combinations with fentanyl in subanalgesic doses was experimentally studied on mice, by using the tail-flick test. Analgesic activity was found in clonidine, antagosane, and transamine. A combination of fentanyl used in subanalgesic doses and clonidine, isradipine, antagosane, or transamine had supertotal analgesic activity. The findings serve as a basis for effectively making up a component of analgesia during anesthetic support at surgery made in patients with baseline sympathicotonia, ischemia/reperfusion syndrome, and a systemic inflammatory reaction.

Effects of apolipoproteins on dalargin transport across the blood-brain barrier.

Antinociceptive activity of dalargin (7.5 mg/kg) adsorbed on poly(butyl)cyanoacrylate nanoparticles with different coating was studied on outbred albino mice by the tail-flick test. poly(butyl)cyanoacrylate nanoparticles without coating did not increase the antinociceptive activity of dalargin and hence, did not increase its transport across the blood-brain barrier. poly(butyl)cyanoacrylate nanoparticles coated with apolipoprotein B, apolipoprotein E, and polysorbate 80 increased the transport of dalargin across the blood-brain barrier. Delivery of dalargin to the brain was most effective in case of using poly(butyl)cyanoacrylate nanoparticles with polysorbate 80 coating and subsequent supercoating with apolipoprotein E.

[Antiamnesic activity of nerve growth factor adsorbed on poly(butyl) cyanoacrylate nanoparticles coated with polysorbate-80].

The antiamnesic activity of nerve growth factor (NGF) in various medicinal forms [aqueous NGF solution with and without polysorbate-80 (PS-80) additives, NGF adsorbed on poly(butyl) cyanoacrylate (PBCA) nanoparticles with and without PS-80 coating] has been studied in rats with model amnesia induced by scopolamine (2 mg/kg, s.c.). The antiamnesic activity was evaluated by the ability of subsequently introduced drugs (5 microg NGF per animal, i.p.) to inhibit the amnesic action of scopolamine as manifested by retrieval of the passive avoidance reflex (PAR) learned using the Lafayette Instruments USP system 30 min after drug injection. The PAR memory trace was evaluated as an increase in the latent time before visiting the dark compartment 24 h after drug injection. In the untreated amnesia control group, the scopolamine amnesia was manifested by the absence of any increase in the PAR latent time. In the form of an aqueous solution, NGF did not inhibit the scopolamine-induced amnesia. NGF adsorbed on uncoated PBCA and in the form of solution with PS-80 produced an antiamnesic action manifested by a reliable increase in the PAR latent time as compared to that in the untreated control group. NGF adsorbed on PBCA nanoparticles coated with PS-80 not only exhibited a significant antiamnesic effect, but even stimulated the cognitive function and increased the PAR latent time above the value in the learned control group.

[Protease inhibitors as an anesthetic component in ENT surgery]. / Primenenie ingibitorov proteaz v kachestve komponenta anestezii v lor-khirurgii.

Both protease inhibitors and transamine should be included in anesthesiologic management of major traumatic operations in patients with initially impaired hemostasis to control inflammatory edema development after operation. As such drugs have an analgesic activity without effect on opiate structures, their different using in combination with narcotic analgesics provides multilevel control for pain conduction that elevates the quality of anesthesia.

[Sandostatin (octreotide)--drug and neurotransmitter (experimental study)]. / Sandostatin (oktreotid)--lekarstvo i neirotransmitter (éksperimental'noe issledovanie).

Sandostatin (octreotide), a synthetic analogue of somatostatin that is a hormone and neurotransmitter of pain conduction, has been developed. The drug has been widely used in gastroenterological care; however, its role as a neurotransmitter has been little studied. The authors performed experimental studies to evaluate the effects of octreotide on the nociceptive sensitivity of animals (the intravenous dose being 1 mg/kg) and on the actinociceptive activity of fentanyl (the intraperitoneal doses, 125 and 250 micrograms/kg). The study has demonstrated that octreotide in a dose of 1 mg/kg causes a steady-state hyperalgesic effect. A combination of octreotide and fentanyl in the above diseases substantially reduces the analgesic activity of the latter just 15 min after injection, which should be borne in mind in applying the above agents in clinical practice.

[The delivery of loperamide to the brain by using polybutyl cyanoacrylate nanoparticles]. / Dostavka loperamida v mozg s pomoshch'iu polibutiltsianoarilatnykh nanochastits.

The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid (lyonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used as the indication of drug transport through this barrier. Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. Polysorbate 80-coated PBCA nanoparticles loaded with loperamide led to the transport of loperamide to the brain.

Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles.

PURPOSE: The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. METHODS: Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. RESULTS: Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. CONCLUSIONS: Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain.

[Transport of the hexapeptide dalargin across the hemato-encephalic barrier into the brain using polymer nanoparticles]. / Transport geksapeptida dalargina cherez gematoéntsefalicheskii bar'er v mozg s pomoshch'iu polimernykh nanochastits.

The drug targeting to the brain by polysorbate 80-coated nanoparticles was studied. The leu-enkephalin analog dalargin was used as a model drug for investigating the drug penetration through the blood-brain barrier. The nociceptive threshold was measured by the tail flick test. The intravenous injection of dalargin bound by sorption to poly(butylcyanoacrylate) nanoparticles subsequently coated with polysorbate 80 induced the analgesic effect in 5.0 and 7.5 mg/kg doses. The pretreatment with naloxone prevented this effect No other controls exhibited the analgesic activity, including the dalargin solution (10 mg/kg, i.v.), dalargin bound to nanoparticles not coated with polysorbate 80; and a simple mixture of dalargin, nanoparticles, and polysorbate 80 mixed directly before the intravenous injection. The luminescent and electron microscopy demonstrated the presence of separate nanoparticles in the capillary endothelium and cerebral neurons, as well as luminescent-labeled polymer in Purkinje's cells of the cerebellum.

[Effect of haloperidol, diazepam and sodium oxybutyrate on the antinociceptive activity of opioid agonists administered via the theca medullaris spinalis]. / Vliianie galoperidola, diazepama i natriia oksibutirata na antinotsitseptivnuiu aktivnost' opioidnykh agonistov pri ikh vvedenii pod obolochki spinnogo mozga.

At intrathecal administration the antinociceptive effect of morphine and DADL significantly exceeds the antinociceptive effect of pentazocine (ED50 in tail flick test were 1.1, 1.64, 75.0 nmol per mouse and in "writhing" test 0.0064, 0.0047, 24.53 nmol per mouse, respectively). All the agonists tested exhibited significantly higher activity at chemical stimulation than at thermal one. During the analysis of pA2 of naloxone during the interaction with morphine, DADL and pentazocine under thermal and chemical stimulation a pronounced mu-receptor component in the effect of DADL and pentazocine was suggested. A preliminary subcutaneous injection of sodium oxybutyrate (150 mg/kg) fails to change the activity of opioids administered intrathecally. Diazepam (5 mg/kg, subcutaneously) enhances the antinociceptive activity of DADL only at chemical stimulation. Haloperidol (2 mg/kg) increases the antinociceptive effect of morphine and DADL at pain stimulation of both types but exerts no influence on the analgesic effect of pentazocine. Haloperidol produces the most pronounced enhancement of the spinal component of delta-agonist DADL antinociceptive action. The enhancing effect of haloperidol is realized at the supraspinal level.

[Changes in the properties of brain opiate receptors during the development of morphine tolerance in rats]. / Izmenenie svoistv opiatnykh retseptorov golovnogo mozga v usloviiakh privykaniia krys k morfinu.

The effects of prolonged administration of morphine on the properties of opiate receptors of rat brain were studied. For this purpose the isotherms of binding of labeled mu-, delta-, and chi-ligands--morphine, D-Ala2, D-Leu5-enkephalin and ethylketocyclazocine--with brain membrane preparations of morphine-tolerant rats as well as those of control animals were analyzed. For quantitative determination of dissociation constants of the ligand-receptor complexes (K) and receptor concentrations ([Q]), the difference and simulation methods were used. It was shown that the values of K and [Q] vary within broad ranges in individual animals, whereas the individual variations of the [Q]/[K] ratios in controls or in morphine-tolerant rats are not so significant. This suggests [Q]/K to be one of the basic criteria for a comparison of properties of opiate receptors in different groups of animals. The use of this criterion and of the simulation method demonstrated that the development of tolerance causes changes in the properties of delta-receptors (the [Q]/K ratio decreases by greater than 50%). Unlike delta-receptors, the tolerance has no appreciable effect on the properties of mu- or chi-receptors or on the superhigh affinity binding sites of the ligands tested.

[Effect of haloperidol on the analgesic activity of opiate agonists administered intracisternally and intrathecally]. / Vliianie galoperidola na anal'geticheskuiu aktivnost' opiatnykh agonistov pri ikh intratsisternal'nom i intratekal'nom vvedenii.

The mu-agonist morphine more actively inhibited the complex reflex manifestations of pain responses (the Hafner test and hot plate) in mice as compared to the spinal pain reflexes (tail flick). The delta-agonist D-Ala2-D-Leu5-enkephalin (DADL) abolished the responses of both types in the same doses. Haloperidol potentiated the ability of morphine and DADL to inhibit nociceptive responses at the cerebral level. The potentiating effect of this neuroleptic on inhibition of spinal nociceptive responses by opiate agonists was only observed at a dose of 5 mg/kg. Haloperidol could also in some of the tests potentiate the antinociceptive effect of the kappa-agonist bremazocine and the sigma-agonist SKF 10.047, however their activity was significantly lower than that of morphine and DADL.