[Experimental kidney transplantation: a comparison between different models]. / Trapianto di rene sperimentale nel suino. Modelli a confronto.

AIM: Two different models of kidney transplantation have been compared using 3 different techniques. The kidney grafts were procured from living donors (laparoscopic or laparotomic technique) and from cadaveric donors. METHODS: Twenty-four outbred piglets (Large White, weight range 24-27 kg) underwent kidney transplantation. We divided the recipients into 2 groups with the following characteristics: group 1 (n=12) was represented by orthopic kidney recipients whose grafts were retrieved by laparoscopic or lapartomic technique from living unrelated donors; group 2 (n=12) was constituted by heterotopic kidney recipients whose grafts were retrieved by laparotomic technique from unrelated cadaveric donors. In both groups, Grogoire-Lich technique and Politano-Laedbetter technique were used in order to perform ureteral-vescical anastomosis together with a new technique developed from our experience called Politano-Laedbetter modified. All transplanted pigs underwent double immunosoppressive steroid therapy (tacrolimus and micofenolate mofetil). The pigs were observed for 60 days. RESULTS: The survival rates in group 1 and in group 2 were 75% (n=9) and 66% (n=8), respectively. No significative differences were noted in length of operative time, creatinemia and ureamia levels in both study groups. The Gregoire-Lich technique was associated with a higher rate of complications. CONCLUSION: Two different experimental models of kidney transplantation are feasible in pigs. The classic technique could be combined with the orthopic one based on the type of study needed.

RP 59037 and RP 60503: anxiolytic cyclopyrrolone derivatives with low sedative potential. interaction with the gamma-aminobutyric acidA/benzodiazepine receptor complex and behavioral effects in the rodent.

This study describes the pharmacological properties of two novel cyclopyrrolone derivatives, RP 59037 [2-(7-chloro-2-naphthyridin-1,8-yl)-3-(5- methyl-2-oxohexyl)isoindolin-1-one] and RP 60503 [2-(7-chloro-2-naphthyridin-1,8-yl)isoindolin-1-yl-4- acetamidobutyrate], in the rodent. These compounds possess high affinity for the benzodiazepine binding site on the gamma-aminobutyric acidA receptor in rat cerebrocortical membranes with Ki values of 0.98 nM (RP 59037) and 1.16 nM (RP 60503). Neither compound discriminates between the putative benzodiazepine BZ1 and BZ2 binding site subtypes present in the rat cerebellum and hippocampus, respectively. Both compounds protect mice against pentylenetetrazole-induced seizures with ID50 values of 0.21 mg.kg-1 p.o. (RP 59037) and 5.96 mg.kg-1 p.o. (RP 60503). The two compounds displayed a restricted anticonvulsant profile compared to diazepam and, in this respect, resembled the pyrazoloquinoline partial agonist, CGS 9896. RP 59037 and RP 60503 were active in two rat models predictive of anxiolytic drug action, a modified Geller-Seifter conflict paradigm (minimal effective dose, 0.33 mg.kg-1 p.o. for RP 59037 and 5 mg.kg-1 p.o. for RP 60503) and the elevated plus maze (minimal effective dose, 0.33 mg.kg-1 p.o. for RP 59037 and 5 mg.kg-1 p.o. for RP 60503). Only very low activities were observed in tests of sedative or myorelaxant effects (ED50 > 50 mg.kg-1 p.o.). It is concluded that the two cyclopyrrolones possess a dissociated behavioral profile, displaying potent anxiolytic and anticonvulsant properties with little or no sedative or myorelaxant effects. Although both compounds appear to be partial agonists at their allosteric recognition site on the gamma-aminobutyric acidA receptor, RP 60503 seems to be more dissociated than RP 59037, which would be compatible with it having lower intrinsic activity. This difference is reflected in a higher receptor occupancy requirement for activity, and a smaller modulatory effect on the binding of t-[35S]butylbicyclophosphothionate.

Pharmacological studies on zopiclone.

Zopiclone (RP 27 267) is an hypnotic with a chemical structure different from that of the benzodiazepines (BZD) or barbiturates. Studies of zopiclone in classical psychopharmacological tests, in comparison with BZD and barbiturates, have shown that it exhibits the five main types of activity considered as characteristic of the pharmacological profile of BZD and partly of that of barbiturates (anticonvulsant, myorelaxant, antiaggressive, sedative-hypnotic and 'anticonflict'). However, like BZD, zopiclone differs from barbiturates by a high safety margin. Electrophysiological studies performed in cats have shown that zopiclone induces modifications in sleep-wakefulness pattern which are close to those observed with BZD, specially with nitrazepam. Moreover, zopiclone increases the threshold for arousal by reticular formation stimulation, rather more than nitrazepam, but with a shorter duration of action. The short duration of action of zopiclone has been demonstrated in other species using different tests.

Pharmacological studies on zopiclone.

Zopiclone (RP 27 267) is an hypnotic with a chemical structure different from that of the benzodiazepines (BZD) or barbiturates. Studies of zopiclone in classical psycho-pharmacological tests, in comparison with BZD and barbiturates, have shown that it exhibits the five main types of activity considered as characteristic of the pharmacological profile of BZD and partly of that of barbiturates (anticonvulsant, myorelaxant, antiaggressive, sedative-hypnotic and 'anticonflict'). However, like BZD, zopiclone differs from barbiturates by a high safety margin. Electrophysiological studies performed in cats have shown that zopiclone induces modifications in sleep-wakefulness pattern which are close to those observed with BZD, specially with nitrazepam. Moreover, zopiclone increases the threshold for arousal by reticular formation stimulation, rather more than nitrazepam, but with a shorter duration of action. The short duration of action of zopiclone has been demonstrated in other species using different tests.