TNF-alpha induced PMN apoptosis in whole human blood: protective effect of SSR180575, a potent and selective peripheral benzodiazepine ligand.

The peripheral benzodiazepine receptor (PBR) has been shown to play a key role in the regulation of the mitochondrial process leading to apoptosis. Despite much controversy in the literature on this subject, PBR synthetic ligands (and specifically agonists such as Ro5-4864 and SSR180575) are described as presenting potent anti-apoptotic effect against oxidative stress, TNFalpha- and tamoxifen-induced apoptosis when the PBR ligand is administrated at a low dose, close to the affinity range of the ligand to its receptor. Such anti-apoptotic activity has already been correlated with a protective effect of PBR ligands against ischemia-reperfusion induced tissue dysfunction. Previously, we had shown that SSR180575 is a specific and high affinity PBR ligand of potential interest in pathological cardiovascular, renal and neurodegenerative indications. Beyond its expression in steroid-producing tissues, heart, liver and kidney, the PBR is also known to be highly expressed in blood cells. In this work, we demonstrate by flow cytometry experiments, that SSR180575, at low concentrations, is able to protect polymorphonuclear leukocytes (PMNs) against TNFalpha-induced apoptosis in whole blood. Thus, in a new context, SSR180575 again shows potent anti-apoptotic properties. Moreover, TNFalpha- induced PMN apoptosis appears to be a good surrogate marker for determining SSR180575 blood availability and activity in treated patients.

Binding characteristics of SSR180575, a potent and selective peripheral benzodiazepine ligand.

The peripheral benzodiazepine receptor (PBR), has been recently shown to play a key role in the regulation of the mitochondrial process leading to apoptosis, which occurs during cardiac ischemia. The present work shows that SSR180575, a novel PBR ligand of potential interest in pathological cardiovascular indications, irreversibly and specifically binds with high affinity on both rat heart mitochondria and on a cell line transfected with the human PBR (K(d)=1.95+/-0.22 and 4.58+/-0.83nM, respectively). In conclusion, SSR180575 is a specific and potent PBR ligand which irreversible binding to PBR appears of high interest in various therapeutic indications where apoptosis occurs.

[The intravital diagnosis of primary pulmonary hypertension]. / Pryzhyttieva diahnostyka pervynnoï lehenevoï hipertenziï.

The authors present a case of during-life diagnosis of primary pulmonary hypertension in a 30-years-old woman. The disease had a two-years history. The peculiarities of this case were incoordinance of asphyxia, cyanosis, hypertrophy of the right heart with the level of pulmonary insufficiency. As to the pathogenetic type this is an acquired plexogenous variant of primary pulmonary hypertension.

[Nature of the estrous cycle, incidence of anovulation, chromosome gametopathies and fetal death in female rats with 2,4-dichlorophenoxyacetic acid (2,4-D) before pregnancy]. / Kharakter éstral'nogo tsikla, chastota anovuliatsii, khromosomnye gametopatii i émbrional'naia gibel' u krys, pri zatravke samok 2,4-dokhlorfenoksiuksusnoi kislotoi (2,4-D) do beremennosti.

The effect of herbicide--2,4-D, injected before pregnancy begins, on the main parameters of the reproductive function of the female rats has demonstrated that chronic administration in doses 1 mg/kg and 12 mg/kg per day for 2 months results in certain disturbances in the estrus cycle, manifesting as prolongation of the diestrus phase and in changes of estrus and meta-estrus++ duration, as well as in an essential increase in rates of anovulatory cycles. Single administration of the preparation during the preovulatory period (50 mg/kg) produces certain disturbances in the chromosomal complex, manifesting as appearance of numerical chromosomal aberrations. When the administration is acute (10 mg/kg and 50 mg/kg) an essential increase of the embryonal death takes place, in the first case--at the expense of ++pre-implantational, and in the second--both at the expense of pre- and ++post-implantational death. At chronic administration increasing rate of the intrauterine death takes place mainly at the expense of ++post-implantational death of embryos.