Studies of mesenteric lymph nodes of rats by indirect immunoperoxidase method using monoclonal antibodies to cytochrome P450 1A/1A2 after oral dose of benzo[a]pyrene showed the presence of these cytochrome forms in monocytes, macrophages, reticular and litoral cells, cell detritus, and liquid contents of the paracortical zone and medullary substance sinuses. Oxidation of various exo- and endogenous toxins in the lymph nodes was revealed.

The lysosomotropic agent chloroquine is widely used as a specific inhibitor of intralysosomal proteolysis in isolated hepatocytes. It was shown that in vitro chloroquine reversibly inhibited purified cathepsins H, B, L in concentrations less than those observed inside lysosomes in vivo. However, administration of high doses of chloroquine to rats (30 -50 mg/kg i.p. as a single or repeated injections) was followed by increased cathepsin D and cysteine proteinase activities, as well as other lysosomal enzymes. Chloroquine administration did not induce any changes of carbon particles phagocytosis by liver cells (macrophages); modifications of fluid-phase ( 125 I-PVP uptake) and receptor-mediated endocytosis ( 125 I-asialo-fetuin uptake) were noted. Chloroquine administered in vivo reproduced some symptoms of lysosomal storage diseases (especially during repeated drug administration).

Preincubation of resident macrophages with 25-hydroxycholesterol decreased the lipopolysaccharide-induced expression of mRNAs of tumor necrosis factor and interleukin-1, while 7-ketocholesterol stimulated the expression of the tumor necrosis factor mRNA. Tolerant macrophages characterized by decreased tumor necrosis factor secretion in response to lipopolysaccharide have increased (in comparison with resident macrophages) content of 25-and 27-hydroxycholesterol.

In atherosclerotic lesions, macrophages are transformed into foam cells accumulating modified low density lipoproteins (LDL) via the scavenger receptor pathway. We have investigated the effects of carboxymethylated beta-1,3-glucan (CMG) on acetylated LDL (AcLDL) metabolism in murine peritoneal macrophages in vitro and upon the clearance of AcLDL by rat liver in vivo. In cultured murine peritoneal macrophages, CMG reduced substantially the AcLDL-induced synthesis of cholesteryl esters, decreased the binding and degradation of [125I]-AcLDL in a dose-dependent manner with complete inhibition at 20-30 nM, but had no effect on the binding and degradation of native [125I]-LDL. In contrast, other polysaccharides studied, namely zymosan lipopolysaccharide, non-modified glucan and mannan Rhodexman, had a slight effect at concentrations significantly exceeding the concentrations of CMG. [125I]-AcLDL injected intravenously into rats was cleared from the blood with a half-life of 3.7 min. About 56 per cent of the label of injected [125I]-AcLDL was recovered in the liver 15 min after administration. Co-injection of the labelled AcLDL with CMG (25 mg kg-1 b.w.) decreased the rate of AcLDL clearance so that the half-life increased to 6.0 min. Injections of CMG (25 mg kg-1 b.w.) 48 and 24 h before the determination increased the rate of [125I]-AcLDL clearance (with a half-life of about 2.3 min) and increased the uptake of AcLDL by the liver. We suggest that CMG competed with AcLDL for scavenger receptors in vitro and in vivo and repeated CMG injections before the measurements of AcLDL resulted in the induction of scavenger receptor function.

BACKGROUND:Clinical conferences are generally defi ned as scheduled events at which practicing physicians themselves present to their colleagues interesting clinical cases, share their new experiences and learn about the latest achievements of medical science and practice. The value of a clinical conference is thought to be in direct communication between physicians, in analysis of topical issues in a given specialty with the aim to improve the quality of care. Speakers based on their own observations and studies reveal the most urgent problems, analyze results and offer potential decisions to their colleagues interested in the same questions. The event format may be different: workshops, highly specialized sections, round tables and seminars with participation of the leading specialists in a given fi eld. These conferences are generally organised by the Ministries and Departments of Health, by leading research and/or educational institutions in the fi eld, by recognised medical centres and other institutions. Recently pharmaceutical companies got actively involved in medical events, acting as sponsors of various scientifi c conferences and congresses, however threatening the mission of these events [1]. This brings up some uneasy questions: who are the medical conferences for? Who is in charge of setting the conference agenda? Do they contribute to evidence-based medicine; do they contribute to better health? Unfortunately, there is a trend to duplication or multiplication of conferences: various agencies and departments deliver the same conferences, presentations at which are often pre-arranged by pharmaceutical companies and do not have clear scientifi c novelty, while the conferences themselves have largely transformed into advertising of new pharmaceuticals or new technologies [2]. Pharmaceutical corporations sponsor invited speakers paying for their trips and paying honoraria, organising cocktail parties as part of medical activities. With the help of leading experts with impressive titles serving as speakers at the conferences, pharmaceutical companies are trying to be as close as possible to routine practice of prescribing of certain drugs, manipulating evidence, controlling scientifi c societies as well as the process of clinical guideline development and publication of research results [3]. The degree of expert involvement depends on their level of infl uence [4].