A cluster of Chlamydia serpentis cases in captive snakes.

Following the occurrence of sudden death cases in a zoo reptile collection, histological analyses conducted on tissues from two common adders suggested an infection due to Chlamydia. The survey was extended to 22 individual snakes from the same collection and a PCR analysis targeting a conserved gene in Chlamydiaceae revealed bacterial shedding in six of them. The infection resolved spontaneously in one snake whereas another one succumbed one month later. The antibiotic treatment administered (marbofloxacin) to the remaining four PCR positive animals stopped the mortalities and the shedding. Analysis of the 16S and 23S ribosomal gene sequences identified C. serpentis, a recently described novel chlamydial species in snakes. A PCR tool for a quick and specific identification of this new chlamydial species was developed in this study.

Immediate and delayed life history effects caused by food deprivation early in life in a short-lived lizard.

Detailed studies of the mechanisms driving life history effects of food availability are of prime importance to understand the evolution of phenotypic plasticity and the capacity of organisms to produce better adapted phenotypes. Food availability may influence life history trajectories through three nonexclusive mechanisms: (i) immediate and long-lasting effects on individual quality, and indirect delayed effects on (ii) intracohort and (iii) intercohort interactions. Using the common lizard (Zootoca vivipara), we tested whether a food deprivation during the two-first months of life influence life history (growth, survival, reproduction) and performance traits (immunocompetence, locomotor performances) until adulthood. We investigated the underlying mechanisms and their possible interactions by manipulating jointly food availability in a birth cohort and in cohorts of older conspecifics. Food deprivation had direct immediate negative effects on growth but positive long-lasting effects on immunocompetence. Food deprivation had also indirect delayed effects on growth, body size, early survival and reproduction mediated by an interaction between its direct effects on individual quality and its delayed effects on the intensity of intercohort social interactions combined with density dependence on body size. These results demonstrate that interactions between direct and socially mediated effects of past environments influence life history evolution in size-structured and stage-structured populations.

omega-[(4-Phenyl-2-quinolyl)oxy]alkanoic acid derivatives: a new family of potent LTB4 antagonists.

A series of omega-[(4-phenyl-2-quinolyl)oxy]alkanoic acid derivatives was prepared which inhibited the binding of the leukotriene B4 to its receptors on guinea pig spleen membranes and on human polymorphonuclear leukocytes. A structure-activity relationship was investigated. The length of the carboxylic acid side chain was important for potent binding activity. The replacement of the oxygen atom at the beginning of the chain with other polar or nonpolar linking groups led to considerable loss of potency, indicating that the oxygen linking atom might be involved in the receptor recognition. alpha-Substitution on the carboxylic acid side chain led to substantially more potent compounds. Substitution on the phenyl ring and on the quinoline ring was also evaluated.

omega-[(4,6-Diphenyl-2-pyridyl)oxy]alkanoic acid derivatives: a new family of potent and orally active LTB4 antagonists.

A series of omega-[(4,6-diphenyl-2-pyridyl)oxy]alkanoic acid derivatives was prepared which inhibited the binding of leukotriene B4 to its receptors on guinea pig spleen membranes and on human polymorphonuclear leukocytes (PMNs) and selectively antagonized the LTB4-induced elastase release in human PMNs. On the basis of these three screens, a structure-activity relationship was investigated. alpha-Substitution on the carboxylic acid side chain led to only small changes in the binding affinities but greatly enhanced the LTB4 antagonist activity. Substitution on the phenyl rings was also evaluated. The terminal carboxylic acid function can be replaced by a tetrazole ring without loss in activity. The best in vitro LTB4 antagonists of this series were investigated in vivo in the inhibition of LTB4-induced leukopenia in rabbits. Compound 9b (RP69698) displayed potent LTB4 antagonist activity, after oral administration, with an ED50 value of 6.7 mg/kg.

Evidence for the existence and ionic modulation of platelet-activating factor receptors mediating degranulatory responses in human polymorphonuclear leukocytes.

High-affinity binding sites for platelet-activating-factor (PAF) have been identified in human polymorphonuclear leukocytes (PMNs). The aim of this investigation was to assess their functional relevance by characterizing PAF-induced elastase release, an enzyme present in azurophilic granules. At 37 degrees C, maximal release (measured with a spectrofluorimetric method) was achieved with 0.3 microM PAF. PAF analogs (e.g. lyso-PAF, 2-O-methyl-lyso-PAF) and enantio-PAF, which exhibit poor PAF-like activity in binding studies, were very weak releasers of elastase. The degranulation induced by PAF was fully and competitively inhibited by RP 59227, a potent, d-enantiomeric PAF antagonist. This effect was stereoselective and specific inasmuch as this compound was 500-fold more potent than its l-enantiomer and was devoid of effects on the degranulation promoted by N-formyl-l-methionyl-l-leucine-l-phenylalanine or [5S,12R]hydroxyeicosa-6,14-cis-8,10-trans-tetraenoic acid. The PAF-induced elastase extrusion was enhanced by physiological concentrations of CaCl2 and MgCl2. For instance, 1 mM Ca++ increased by 200% the release produced by 100 nM PAF. The mechanism of this effect is probably related to the capability of Ca++ and Mg++ to enhance the maximum number of [3H]PAF binding sites in whole or lysed PMNs without affecting the affinity (Kd) of the ligand. An additional possibility is that these ions intervene at the level of the signal transduction system leading to degranulation. For a series of 22 known PAF receptor antagonists, belonging to different chemical families, there was a strong correlation (r = 0.95) between their ability to displace [3H]PAF and to inhibit the PAF-evoked elastase release.(ABSTRACT TRUNCATED AT 250 WORDS)

[3H]52770 RP, a platelet-activating factor receptor antagonist, and tritiated platelet-activating factor label a common specific binding site in human polymorphonuclear leukocytes.

In human polymorphonuclear leukocytes (PMNs), the tritiated platelet activating factor ([3H]PAF) labels in a saturable manner a single class of binding sites with a Kd of 3.5 +/- 0.5 nM (n = 7) and a maximum binding capacity (Bmax) of 206 +/- 13 fmol/2.5 X 10(6) PMNs (n = 7). 52770 RP, a nonphospholipid antagonist of PAF receptors, fully and competitively displaced the [3H]PAF from its binding sites with a Ki of 7.0 +/- 0.7 nM (n = 4). The high potency and the low solubility in cellular membranes of this compound led us to prepare [3H]52770 RP. This ligand was characterized by a binding which was rapid, reversible, confined to a single site, saturable, specific and stereoselective. Its Kd and Bmax were 4.2 +/- 0.3 nM and 181 +/- 11 fmol/2.5 X 10(6) PMNs, respectively. The stereoselectivity of the binding was suggested by the 600- and 1050-fold higher potency of the d-enantiomer with respect to l-52770 RP in displacing [3H]52770 RP or [3H]PAF, respectively. Several PAF analogs (e.g., lyso-PAF, 2-O-methyl-lyso-PAF), which are poorly active as PAF receptor agonists in functional tests, were weak displacers of [3H]PAF and [3H]52770 RP. Furthermore, for a series of 14 known PAF receptor agonists or antagonists belonging to different chemical families, there was an excellent correlation (r = 0.98) between their ability to displace [3H]PAF and [3H]52770 RP. Thus, [3H]52770 RP and [3H]PAF appear to interact with the same binding site on human PMNs which is proposed to be the PAF receptor mediating functional responses.(ABSTRACT TRUNCATED AT 250 WORDS)