Antagonist effects of the enantiomers of 3-PPP towards alpha 1-adrenoceptors coupled to inositol phospholipid breakdown in the rat cerebral cortex

The effects of the two enantiomers of 3-PPP upon alpha 1-adrenergic and muscarinic receptors coupled to the inositol phospholipid (PI) breakdown response have been investigated. 3-PPP(-) and 3-PPP(+) were found to antagonize the noradrenaline (10 microM)-stimulated PI breakdown in rat cerebral cortical miniprisms with IC50 values of 18 and 61 microM, respectively. The dopamine receptor antagonists haloperidol and raclopride were also antagonists, with IC50 values of 0.4 and 25 microM, respectively. 3-PPP(-) and raclopride were found further to act as competitive antagonists, with pA2 values of 6.03 and 5.44, respectively. 3-PPP(-), 3-PPP(+) and haloperidol also antagonized the muscarinic receptor-mediated carbachol (50 microM)-stimulated PI breakdown in cortical miniprisms, albeit at high concentrations (IC50 values of 91, 170 and 28 microM, respectively) whereas raclopride produced only 24% inhibition at the highest concentration tested (100 microM).     

Postural responses to lateral perturbation in healthy subjects and ankle sprain patients.

The purpose of this study was to investigate postural responses of healthy subjects and patients with recent ankle sprains following a perturbation that created sway in the frontal plane. EMG data were taken from the posterior tibialis (PT) (not monitored in patients), peroneal longus (PL), and tibialis anterior muscles (TA). Subjects stood on a platform that provided a rotational perturbation (approximately 70 degrees.s-1) in the frontal plane. This perturbation had the effect of everting and loading one limb while inverting and unloading the contralateral limb. An initial response in the PT of the loaded limb and the PL of the unloaded limb was noted at approximately 50 ms following the perturbation. This was followed by a bilateral response in the TA at 60 ms. The amplitude of the TA muscle was significantly greater in the loaded limb. For ankle sprain patients a bilateral TA response and a PL response in the unloaded limb was noted at approximately 65 ms. TA response amplitude ratios between the loaded and unloaded limbs were similar to that of the healthy subjects. These data suggest that ankle sprain patients use a modified postural response following lateral perturbation as a compensation for the injury.     

Stereoselective inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by 4-dimethylamino-2,α-dimethylphenethylamine (FLA 336)

Summary The in vitro inhibition by amiflamine [FLA 336(+)] and related compounds of the activity of rat monoamine oxidase (MAO)-A and-B, rat semicarbazide sensitive amine oxidase (SSAO) and human platelet poor plasma benzylamine oxidase was studied. Amiflamine was an MAO-A selective inhibitor, but also inhibits SSAO with both a reversible (competitive, K _i=200 mol/l) and a small time-dependent component which was irreversible in nature. The optical isomer FLA 336(–) was ten times less potent towards MAO-A. However, this compound was much more potent an inhibitor of SSAO (competitive, K _i=4.6 mol/l). The amiflamine metabolites FLA 788(+) and FLA 668(+) inhibited SSAO, but only at concentrations considerably higher than required for MAO-A inhibition. Ex vivo experiments indicated that there was no significant irreversible inhibition of rat heart and lung SSAO after both single and repeated administration of amiflamine at doses up to 20 times higher than required for inhibition of MAO-A within central serotoninergic neurones.     

Characterization of lymphoid cell populations in bovine lymphosarcomas (“leukosis”) by flow-cytofluorometry

Acridine orange stained cell suspensions from ten cases of bovine lymphosarcoma were analyzed by flow-cytofluorometry. The green DNA-AO fluorescence showed in all cases, but one, two distinct separate lymphoid cell subpopulations. One corresponded to (normal) diploid lymphoid cells, the other had variable aneuploid values. The histograms of the latter cell populations also indicated cells in S- and G₂-phase. Low-angle light scatter histograms did not show a distinct separation between the different cell types, although two maxima could be distinguished. The relative proportions between the two cell populations varied between 20 and 80% with domination of one or the other cell type.There was some conformity to the histological and cytological picture in the ordinary light microscope, although neither a clear distinction in separable cell types nor differential counts was possible.The diploid lymphocyte subpopulation in the tumor might represent an immunoreactive process against the BLV-induced lymphosarcoma.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Influence of LH/FSH releasing hormone (LRH) on the basal secretion of gonadotrophins in relation to plasma levels of oestradiol, progesterone and prolactin during the post-partum period in lactating and in non-lactating women.

The pituitary responsiveness to LH/FSH releasing hormone (LRH) was studied in the puerperium in lactating and in non-lactating women. The response of both groups of patients to 25 mug LRH iv was tested 8-10 days, 15-17 days, and 29-32 days after a normal delivery at full term. The basal levels of FSH were low during the first 10 days after delivery. A rise was then observed, and about 4 weeks after delivery levels above or in the upper normal range of a normal follicular phase were recorded. The levels were significantly higher in the lactating group. When compared with the normal follicular phase, the relative increase in FSH basal levels was higher than the increase in LH basal levels in both groups of patients. The period of non-responsiveness of the pituitary to LRH was found to be of equal length in the two groups. In both groups the FSH response returned more rapidly than the LH response. About 2 weeks after delivery a reverse pattern of gonadotrophin response to LRH was seen with a FSH response that was greater than the LH response compared with what is generally observed in the various phases of the menstrual cycle in eumenorrhoeic women. This pattern was more pronounced in the lactating group about 4 weeks after delivery. Oestradiol levels were low and roughly equal on the three test occasions in each group, but in the non-lactating group there was a tendency to higher concentrations. Prolactin levels were highest about one week after delivery and then showed a tendency to decrease, and this was more pronounced in the non-lactating group. Progesterone levels were invariably low in both groups.