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Inflammatory reactions induce the production of reactive oxygen species (ROS): the reverse sequence of these events is also true. Moreover, many components of these reactions interact with a synergistic effect. In this short comprehensive review we analyze some of these interactions which may have pathological effects. Inflammatory reactions are triggered off by exogenous or endogenous aggressions and are characterized by cellular and vascular events. The activated leucocytes leave the circulating blood and reach the site of the aggression where they release a large amount of ROS as well as the content of their granules. The granular content is made in a large part by molecules with killing and degradative activities such as myeloperoxidase, defensins, elastase, collagenase, cathepsins and lysozyme. The inflammatory reaction is beneficial for humans when its effects are limited to the pathogens. The insufficiency of a component of the inflammatory reaction such as the production of ROS which is seen, for example in chronic granulomatous disease, leads to severe and recurrent bacterial infections. In other situations inflammatory reactions are deleterious because they are directed against normal tissues instead or in addition to pathogens. In some cases the behaviour of the phagocytes is modified because they have been primed by inflammatory molecules such tumor necrosis factor, LPS, interleukins or interferons. Priming often leads to a decreased speed of locomotion of the leucocytes with an increased susceptibility to their stimuli. The combination of these effects leads to a premature release by the phagocytes of their killing and degradative factors. Production of ROS such as that seen during irradiation, drug metabolism, or ischemia followed by reperfusion for example, induces inflammatory reactions with a secondary amplification of ROS production. Acute ROS production can also lead to thrombosis, whereas chronic ROS production can induce a chronic inflammatory reaction of the endothelium with atherosclerosis as a possible consequence. Some examples are also given to show that ROS might control positively or negatively the activity of inflammatory molecules. The multiplicity of the cross reactions between ROS and inflammation allows to suggest that drugs that disconnect these two events might be therapeutically used.

When appropriately stimulated, monocytes are able to initiate blood coagulation through the membrane expression of tissue factor. This procoagulant activity is thought to play a role in activating coagulation in response to inflammatory stimuli in vivo. We found that pentoxifylline, a methylxanthine derivative already reported to regulate some monocyte functions, inhibits the procoagulant activity developed by monocytes in vitro in response to endotoxin. This effect was accompanied by an early increase in intracellular levels of cyclic AMP and was mimicked by compounds that induce an increase in cyclic AMP levels. These results suggest that the suppressive effect of pentoxifylline occurs at least in part via an increase in intracellular cyclic AMP levels.

Simultaneous inversion of the anteroposterior and dorsoventral axes of the lateral mesoblast in the early toad neurula leads to the total agenesis of the urogenital organs. The experimental results show that the lateral mesoblast is unable to undergo self-differentiation, and that three factors at least are required for the formation of the urogenital blastemata. The mesoblast must be competent: only the posterior (dorsal, but also ventral) part of the lateral mesoderm is endowed with this competence. It must receive two stimulating influences, from the cordomesoblast on the one hand, and from the dorsocaudal endoblast on the other hand.

The monovalent reduction of oxygen yields two reduced intermediate forms: the dioxide anion (O2), hydrogen peroxide H2O2, and the hydroxyl radical (OH.) several of which appear as radicals. Under normal conditions, the concentration of free oxygen radicals in the tissues is closely controlled because of the serious cell lesions which an accumulation of these radicals can cause. The aim of this paper was to discuss the origin and role of free oxygen radicals in cell lesions induced by myocardial ischemia/perfusion as well as results obtained in different experimental models using methods to trap these radicals. Overall these experimental results are encouraging and appear to offer new therapeutic possibilities which, however, have been evaluated only barely in man.

Blood polymorphonuclear neutrophils defend man against aggressions from pathogens. Under the combined influence of granulocytic and non-granulocytic factors, the defensive process develops by steps: the neutrophil moves towards the pathogenic organism which, one reached, is engulfed and killed. The killing systems of the cell are either oxygen-dependent or independent. the oxygen-dependent system is triggered off by stimulation of the cell membrane and involves various reactions, including cyanide-resistant oxygen consumption, production of activated oxygen, oxygen peroxide and halogenisation of the pathogen membrane. Impairment of the killing activity requires quantitative assessment of its various components in the presence of autologous or control serum with the view of: determining the origin (granulocytic or non-granulocytic) of the impairment, and identifying the step in oxygen metabolism that is affected. In the vast majority of non-granulocytic insufficiencies the cause lies in defective opsonins. In granulocytic insufficiencies, global failure of the system indicates chromic granulomatous disease, a syndrome that is now being dismembered. Defective halogenisation should lead to testing for deficiency of myeloperoxidase or abnormal degranulation. The non oxygen-independent bactericidal system, although highly effective in vitro, appears to be less important in vivo than the oxygen-dependent system. Little is known of its pathology.

Roxithromycin (RU 28965) a new semisynthetic macrolide has been reported to display an antibacterial spectrum and activity in vitro similar to those of others macrolides. However, roxithromycin seems more efficient than erythromycin in in vivo experimental infections (mice). We have previously reported that roxithromycin increases the ability of human neutrophils (PMN) for bactericidal activity (S. aureus) or phagocytosis (K. pneumoniae) in vitro without altering other PMN functional parameters. In this study, roxithromycin (single dose-300 mg) was given to 6 human volunteers. The neutrophils collected 90 min after ingestion display a significant increased ability to phagocytose and kill S. aureus and K. pneumoniae. Furthermore chemotaxis, oxidative burst and myeloperoxidase activity of the PMN after roxithromycin ingestion were enhanced compared to those of PMN before ingestion. This discrepancy between immunomodulating effect of roxithromycin in vitro and in vivo outlines the complexity of in vivo experimental models and requires further studies in vivo in particular in patients suffering from sepsis.

Since July 1st, 1958, we have operated 1095 patients with some hematological disease. We review the chief currently accepted surgical indications for splenectomy (Hodgkin's disease no longer being one of them, or seldom so), and we communicate our results pertaining to the immediate postsurgical period. Mortality and morbidity have been 1.36% and 3.28%, respectively. In over 95% of cases, there have been no complications. The low incidence (1.36%) of infection-related complications was partly due to the important number of splenic drains placed. High quality results can only be achieved when tight collaboration exists between hematologists, radiologists and surgeons.

The experimental results of cranio-caudal reversal and dorso-ventral reversal of the lateral mesoblast of the toad early neurula prove that, at this stage, the cranio-caudal polarity of this tissue is fixed but not the dorso-ventral one. External factors are responsible for the formation of mesonephric, adrenal and gonadal medullary anlage by the lateral mesoblast.

We report the prenatal diagnosis in a 20 week male fetus at risk of chronic granulomatous disease (CGD). A previous affected brother was known in the family and the mother was detected as heterozygote. Three different assays were performed on fetal blood obtained under fetoscopy: cytochemical reduction of nitroblue tetrazolium (NBT), chemiluminescence after activation by opsonized zymosan or phorbol myristate acetate (PMA) and production of superoxide anion (O2-.). Results were comparable to those obtained in 6 fetuses investigated for other inherited diseases. Absence of functional polymorphonuclear defects was confirmed at birth. The use of 3 different techniques performed on whole blood for prenatal diagnosis of CGD has to be recommended instead of an isolated technique adapted to whole blood tests.

At early neurula stage of the toad, cranio-caudal and dorso-ventral reversal of lateral mesoblast is performed. The genito-urinary system is therefore missing after this intervention. The three following factors of the formation of this system anlage are anlyzed: lateral mesoderm competence, stimulative activites of dorso-caudal endoblast on the one hand, of chordo-mesoderm on the other hand.

Polymorphonuclear functions were studied in 3 patients of the same brotherhood with Papillon-Lefèvre disease (hyperkeratosis palmaris and plantaris and acute periodontosis resulting in loss of teeth) who developed severe and recurrent infections. Chemotaxis, oxygen consumption and production of H2 O2 were investigated by polarography, O2 production by quantitative reduction of nitroblue tetrazolium and iodination by the Pinus and Klebanoff technique. functional anomalies of polymorphonuclears involving chemotaxis, induced O2 consumption and H2 O2 production were detected in all three patients. This study confirms the presence of polymorphonuclear functional anomalies in patients with Papillon-Lefèvre disease. Analysis of the family tree of the patients, which went back to 1761, showed that this was probably not a chance association.

Anteroposterior inversion of lateral mesoblast of early toad neurula is followed by differentiation of diverse urogenital blastema, according to the transplant position before the graft. Anteroposterior polarity of lateral mesoderm is thus perfectly determined in young neurula. On the contrary, dorsoventral inversion of lateral mesoblast leads to mesodermic blastema formation according to the transplant position after the graft. Particularly, the dorsal region of the lateral plates displaced to ventral position does not form blastema. On the other hand, the ventral region which shows a dorsal position after the graft develops and produces a typical blastema. Thus, in the young neurula, the dorsoventral polarity is not yet determined in the lateral plate of the mesoblast. Such a result shows also that the ventral and posterior regions of the lateral mesoblast are competent to form blastema. Moreover, factors from dorsal origin and external to lateral mesoblast take part in urogenital organ anlagen formation.

Clinical and biological features of a recently recognized inherited syndrome are reported. This syndrome, Leukocyte Adherence Deficiency, is characterized by recurrent, life-threatening infections. The increased susceptibility to infectious agents is mainly related in the inability of the leukocytes to adhere to certain surfaces, because all adherence-related functions of the neutrophils that lead to bacterial killing are impaired. Adherence deficiency is due to moderate or severe deficiency of three structurally related glycoproteins (MO1, LFA-1 and gp 150,95). All three glycoproteins are heterodimers and share a common subunit whose absence is the cause of the disease.

Phagocytes (P), i.e. neutrophils, monocytes and macrophages, may be involved as well as reactive oxygen species (ROS) in the initiation and development of atherosclerosis. Evidences for this assumption are the following; P and ROS are both able to damage endothelial cells whose dysfunction is crucial in the etiology of atherosclerosis. ROS generated by endothelial cells, smooth muscle cells or mainly blood cells such as neutrophils but also monocytes platelets and erythrocytes, peroxide directly endothelial cell membranes. Damage to cell membranes can be induced by P that adhere to, and release on endothelial cells large amounts of proteolytic and lipolytic enzymes. ROS can also induce formation in the blood of lipoperoxides which are often included in LDL (low density lipoproteins). These modified LDL are cytotoxic, possess phospholipase A2 activity and are recognized by the LDL scavenger receptor which is on the monocyte-macrophage membrane. The modified LDL are also immunogenic inducing formation of autoantibodies directed against them and normal LDL. Modified LDL and LDL immune complexes can be ingested by monocytes leading to foam cells and ROS. The damaged endothelial cells have an increased permeability to macromolecules, synthetize chemotactic factors, decrease their prostacyclin production and favour the adherence of neutrophils and monocytes to their surface. All these factors could increase ROS production and lipid peroxidation amplifying intra and extra-cellular accumulation of lipoperoxides in vascular walls. The ability of ROS and P to damage endothelial cells, to induce lipid peroxidation and thus to be involved in atherosclerosis relies on in vitro experimental results.(ABSTRACT TRUNCATED AT 250 WORDS)