[Oculo-orbital changes in osteopetrosis]. / Modificari oculo-orbitare în osteopetroza.

Osteopetrosis means a low function of osteoclasts, that induces bone resorption with a decrease in bone density. It has two genetic forms: a benign form with autosomal dominant inheritance (AD) and a malignant form with autosomal recessive inheritance (AR). The most successful therapy is bone marrow transplantation (rate of success 80%). We will present a case of malignant osteopetrosis of a five years old child. The late diagnosis (at 18 month) and the malignant evolution has made possible only palliative treatment, without surgical or ophthalmologic-neurosurgical implication. The prognosis is unfavorable with 70% survival to six years and 30% to ten years.

Effect of trace element combination on the immune response of rats treated with cytostatic drug.

The effect of trace element combination, Béres Drop Plus (BDP) on the immune response of rats following single treatment with cytostatic drug (5-fluorouracil, 5-FU) was tested. Animals were treated with 5-FU and SRBC simultaneously, but separately. Rats were pretreated with BDP for 21 days. The body and spleen weight, furthermore the number of spleen cells and antibody producing cells were determined. The antibody titres in blood serum were also measured. The immune system of rats, 5 days following the 5-FU treatment, showed considerable regeneration. Pretreatment of rats with BDP had a beneficial effect on all parameters investigated.

Effect on the immune system of mice exposed chronically to 50 Hz amplitude-modulated 2.45 GHz microwaves.

The effect of continuous (CW; 2.45 GHz carrier frequency) or amplitude-modulated (AM; 50 Hz square wave) microwave radiation on the immune response was tested. CW exposures (6 days, 3 h/day) induced elevations of the number of antibody-producing cells in the spleen of male Balb/c mice (+37%). AM microwave exposure induced elevation of the spleen index (+15%) and antibody-producing cell number (+55%) in the spleen of male mice. No changes were observed in female mice. It is concluded that both types of exposure conditions induced moderate elevation of antibody production only in male mice.

The effect of trace elements on the immune response of rats with intact or injured immune system.

We studied the effect of a trace element combination (Béres Drop Plus; BDP) on the immune response of rats, with intact and with injured immune system. Rats were treated with different doses of BDP for 26 days. The immune system was injured by 7.0 Gy whole body gamma irradiation on the first day of BDP treatment. Rats were immunized on the 31st day of the BDP treatment with sheep red blood cells. In the spleen the cell count and the number of antibody producing cells were determined. In the serum the titre of hemolysin was tested. In rats with intact immune system all used doses of BDP induced elevation of the immune response. The moderate high doses were especially effective. In rats with injured immune system the effect was less. Only the 250 microliters/kg body weight dose could elevate the immune response, and the highest (500 microliters/kg) dose reduced the response.

Suppression of endotoxin mitogenicity of spleen cells by lipoxygenase inhibitors and its reversal by 13-hydroxyoctadecadienoic acid.

The effects of several inhibitors of lipoxygenases were investigated in murine spleen cell cultures activated with endotoxin (lipopolysaccharide). It was found that these inhibitors interfere with the proliferative response of the cultures. Indomethacin, a specific cyclooxygenase inhibitor, had no such effect. Endotoxin induced the synthesis of tumour necrosis factor alpha in spleen cells which was prevented by treatment with a lipoxygenase inhibitor. The inhibition of the mitogenic effect of endotoxin could be reversed by addition of 13-hydroxyoctadecadienoic acid. This was not the case with leukotriene B4 and C4 or 15-hydroxyeicosatetraenoic acid. In contrast, these substances had inhibitory effects on the mitogenicity of spleen cells. It is suggested that 13-hydroxyoctadecadienoic acid is involved in the development of the mitogenic reaction, possibly on the level of tumour necrosis factor alpha production of macrophages present in the cultures.

Mononuclear phagocytes and eicosanoids: aspects of their synthesis and biological activities.

Mononuclear phagocytes convert arachidonic acid and other unsaturated fatty acids from intracellular sources to a variety of oxygenated metabolites such as prostaglandins and leukotrienes which are secreted into the surrounding medium. Other oxidative products such as hydroxylinoleic acids are reacylated into cellular constituents. The underlying metabolic pathways are activated by numerous stimuli of exogenous or endogenous origin. Depending on the state of activation and cell differentiation, the organ of origin and the nature of the stimulus used, macrophages elaborate a distinct spectrum of oxidative arachidonic acid metabolites. The contribution of these metabolites to the proinflammatory properties of macrophages is twofold: As autocrine signals they modulate the synthesis of diverse macrophage products and they influence cellular functions of other cells such as T-lymphocytes.

Alterations in the chemical composition and antigenicity of Escherichia coli O89 lipopolysaccharide and lipid A after 60Co gamma irradiation.

The chemical composition and the antigenicity of Escherichia coli lipopolysaccharide (LPS) and lipid A were investigated after irradiation with 150 kGy 60Co-gamma ray. Compared to the original preparations, the irradiated LPS showed a significant reduction in glucosamine, glucose and galactose and a decrease in the phosphate content. The fatty acid components were reduced to a smaller degree. Irradiation induced a reduction in the antigenicity of the polysaccharide part. The amount of glucosamine and phosphate decreased in the irradiated lipid A. The fatty acid content was significantly reduced. The alteration in the chemical composition was not paralleled by changes in the antigenicity of irradiated lipid A.

PHA- and Con A-induced chemiluminescence of human blood mononuclear cells and granulocytes in luminol or lucigenin.

Phytohemagglutinin (PHA) and concanavalin A (Con A) can evoke a chemiluminescence (CL) response both in granulocytes and blood mononuclear cells. We have used two parallel systems to compare the quantity and quality of oxygen radicals produced during activation. While the luminol-enhanced CL response is linked to the myeloperoxidase-H2O2-chloride system, the lucigenin-dependent light production measures only the superoxide radical. PHA produced higher CL response in the presence of luminol than with lucigenin. Con A showed high CL response only in the lucigenin-enhanced system. The results suggest that while Con A induces mostly superoxide production, the membrane stimulus evoked by PHA produces light through the myeloperoxidase-H2O2-halide system. Granulocytes are less sensitive to PHA than the blood mononuclear cells. The sensitivity of the responses to several scavengers and enzymes support the differential production of oxygen radicals following activation via these two lectins.

In vivo and in vitro effect of toxic and radio-detoxified endotoxin preparations on chemiluminescence of peritoneal cells of mice.

Chemiluminescence (CL) of peritoneal cells was investigated one and five days after injection of toxic and radio-detoxified endotoxin. The CL was triggered by toxic and radio-detoxified endotoxin. The radio-detoxified endotoxin has less pronounced in vivo activating effect than the toxic endotoxin. As triggering agent the toxic endotoxin was more effective than the radio-detoxified endotoxin. However, the radio-detoxified endotoxin has preserved some in vivo activating and in vitro triggering effect.

Age dependent effect of toxic and detoxified endotoxins on the natural anti-DNA antibody level in rats.

Toxic endotoxin (LPS) and its irradiated detoxified form (RD-LPS) induced only small changes in the DNA level in the sera of 4, 12 and 18 months old rats. Changes in the anti-DNA titres were age-dependent. In 4 months old rats one or two injections of the LPS preparations failed to increase the circulating anti-DNA level. In 12 and 18 months old rats both toxic and detoxified LPS preparations raised the anti-DNA titres. The second LPS injection evoked a smaller response in 18 months old rats than the first one.

Induction of human rheumatoid factor and other autoantibodies by bacterial lipopolysaccharide.

In vitro autoantibody production induced by lipopolysaccharide (LPS) was studied using peripheral blood mononuclear (PBM) cell suspensions from patients with rheumatoid arthritis (RA) and healthy subjects. PBMs from both groups could be induced by LPS to secrete IgM and IgA rheumatoid factors (RF), antinuclear and anti-beta-2-microglobulin autoantibodies. Spontaneous production of IgM-RF was considerably higher in RA than in controls. The rate of IgM-RF and IgA-RF secretion detected by ELISA increased with the dose of LPS in cultures of both groups. In RA, differences were found between the kinetics of IgM- and IgA-RFs secretion. LPS augmented the relative avidity of IgM-RF produced by PBMs from RA patients and this value was significantly higher than that of healthy persons. In some cases RFs cross-reacting with nuclear antigens and beta-2-microglobulin were detected.

Endotoxin tolerance in rats treated with antilymphocyte serum.

Rats were treated with rabbit anti-rat lymphocyte serum (ALS). The subsequent selective immunosuppressive effect on the immune response of thymus dependent antigen was shown by immunization with sheep red blood cells (SRBC). Endotoxin tolerance could be evoked in ALS treated animals. This suggests that the establishment of endotoxin tolerance is independent of thymus function and makes it possible to enhance the nonspecific resistance of immunosuppressed patients with a transplanted organ.