A series of novel, highly potent and selective agonists for the kappa-opioid receptor.

1. This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. 2. These compounds all showed potent, naloxone-reversible, full agonist activity in the field-stimulated rabbit vas deferens, indicating that they are kappa-opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to mu- and delta-opioid receptors. 3. They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4. It is concluded that the seven novel compounds described are all potent and selective agonists for the kappa-opioid receptor.     

Ausfallhonorar wegen Nichterscheinens zu einem Exklusiv-Termin

Abstrakt 1. Nimmt ein Patient einen ihm von seinem (Zahn-)Arzt einger?umten Exklusiv-Termin nicht wahr, obwohl er auf dessen Eigenschaft ausdrücklich hingewiesen wurde, so hat er dem (Zahn-)Arzt den Behandlungsausfall abzüglich eines angemessenen Eigenanteils des (Zahn-)Arztes zu ersetzen. 2. Die Ersatzpflicht tritt auch dann ein, wenn der Patient den Termin nicht in der in dem Behandlungsvertrag vorgesehenen Frist absagt. Eine hierfür seitens des (Zahn-)Arztes bestimmte Frist von zwei Tagen vor Behandlungsbeginn stellt sich für den Patienten grunds?tzlich auch nicht als unangemessene Benachteiligung i.S. des § 307 BGB dar. 3. Ein Anspruch des Arztes entf?llt auch bei nur mündlicher Vereinbarung nicht unter dem Gesichtspunkt des § 4 Abs. 5b BMV-Z, denn diese Vorschrift ist teleologisch dahin zu reduzieren, dass nur zahn?rztliche Honoraransprüche aus erfolgten Behandlungen schriftlich vereinbart werden müssen. Soweit es jedoch um einen vertraglichen Anspruch wegen einer Leistungsst?rung geht, vermag das Schriftformerfordernis des § 4 Abs. 5b BMV-Z grunds?tzlich nicht einzugreifen. (Leits?tze des Bearbeiters)     

Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.      

Serum concentrations of oestradiol-17beta, progesterone, relaxin and chorionic gonadotrophin during blastocyst implantation in natural pregnancy cycle and in embryo transfer cycle in the rhesus monkey

The present study was undertaken to assess the temporal association between the profiles of serum concentrations of oestradiol-17beta, progesterone, chorionic gonadotrophin (CG) and relaxin in pregnancies established naturally, and after embryo transfer, as well as in failed pregnancies in rhesus monkeys. In naturally mated cycles (group 1) a conception rate of 75% was obtained. In group 1, the mean day of CG detection in serum was 11.5 +/- 1.9 day post-ovulation, and for relaxin, 9.0 +/- 2.5 day post-ovulation. In group 2, embryo transfer to synchronous, non-mated surrogate recipients was performed; seven embryo transfer cycles yielded three pregnancies which were allowed to continue to term and normal infants were delivered. In embryo transfer cycles the mean day of CG detection was 14.8 +/- 1.8 day post- ovulation, and for relaxin, 11.4 +/- 2.6 day post-ovulation. A delay of about 3 days was observed in the appearance in circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between natural mated and embryo transfer conception cycles. Significant differences (P < 0.05 for progesterone and P < 0.03 for oestradiol) were obtained for the areas under the curves for progesterone and oestradiol between days 12 and 16 in conception cycles compared with failed pregnancies. These data provide the first observation of the normal hormonal signals associated with maternal recognition of transferred embryos during the peri- implantation period, and suggest that the use of such an experimental primate embryo transfer model may help to elucidate components of maternal and embryonic signal-response mechanisms during embryo implantation.      

A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection

A rapid microagglutination test has been developed which can be performed in 30 minutes. Ninety-seven percent of 96 patients diagnosed as having Legionella pneumophila (serogroup 1) infection by indirect immunofluorescence were also detected by the rapid microagglutination test.     

Life expectancy in British Marfan syndrome populations

A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome.