Detection of antiendothelial cell antibodies in patients with connective tissue diseases by flow cytometry and their relation to endothelial cell activation.

Antiendothelial cell antibodies (AECA) have been detected by flow cytometry analysis in 23 out of 80 patients with connective tissue diseases. Ten out of 19 serum samples from patients with systemic lupus erythematosus (SLE) were positive. These antibodies were not detectable in healthy donors. We examined the capacity of serum samples to induce endothelial cell activation by modulating cell adhesion molecule expression on human umbilical vein endothelial cells. We found that sera from both AECA-positive and AECA-negative patient groups induced a significantly higher expression of E-selectin compared to healthy controls (P<0.05). There were no differences in the ICAM-1 on VCAM-1 expression. Our data suggest that increased E-selectin expression in activated endothelium in patients with various connective tissue disorders is not related to the production of AECA.

Civilization as a threat to human health?

Civilization can be defined as the distinctly human attributes and attainments of a particular society. In general, the development of civilization is viewed as a positive step for the well-being of the human species, leading to an increased duration and quality of human life. The accelerated progress of civilization (mainly industrialization, urbanization and nutrition) has lead to new possibilities for adverse effects on human health. A collection of problems referred to as 'civilization diseases' has become the subject of serious concern but review of available data indicates that this concept appears to add very little to our understanding of modern environmental influences on human health. Important limitations in the continued use of this term are its non-specificity, the lack of a unifying scientific foundation, and provision of virtually no direction for remediation of these diseases or for future research. In addition, the use of this term has been localized to primarily post-socialist European countries. In view of these limitations, it seems more productive for scientists, in all parts of the world, to embrace the discipline of environmental health science and to discontinue use of the term "civilization diseases".

[The vascular endothelium in inflammatory processes in vivo and in vitro]. / Cievny endotel v zápalovom procese in vivo a in vitro.

Endothelial injury occurs in atherosclerosis, infectious, rheumatic and vasculitic processes, leading to activation of transcription factors and endothelial expression of various cytokines and adhesion molecules. Endothelial cell cultures represent a valuable tool in research activities, with emphasis on the principal characteristics of angiogenesis, inflammatory response, transduction signals and endothelial functionality. In the laboratory of tissue cultures we prepared primary endothelial cultures by their isolation from the umbilical vein. This model system has been used to investigate the endothelial activation in vitro, adhesion alterations of immunocompetent cells to endothelium, adhesion molecule expression in the disease course monitoring and anti-inflammatory treatment. (Tab. 1, Fig. 5, Ref. 45.)

[Epileptic seizures and immune disorders]. / Epileptické záchvaty a poruchy imunity.

UNLABELLED: The links of epileptic seizures with febrile diseases, as well as with common infections are generally known. Similarly, physicians are aware of the coincidence of epileptic activity with immunity disturbances, as well as of the effects of the antiepileptic drug phenytoin on the immunity system. Disturbances of immunity are commonly reported in 30% of the population. Our clinic is a consilliary regional centre for torpid epilepsies and sleep defects. The aim of study is to document the occurrence of immunity disturbances in unsuccessfully treated patients (5-25 years of age) with generalised convulsive epilepsy (GENKONV-GK) in a group containing 50 patients, and with partial epilepsy with complex symptomatology (PARTKOMP-PK) in a group containing 75 patients. At the same time, this studys objective resided in seeking evidence of the positive effect of immunomodulatory therapy. In all patients, the basic diagnosis had been stated in coincidence with the origin of epilepsy during hospitalisation in neurologic wards. In 1993-1995 our clinic supplemented the electrodiagnosis by a series of routine EEG which was focused at the recurrence of the disease. As a rule, each of the patients was subdued to a 24-hour EEG monitoring on the 12-canal apparatus. Individual supplementation by CT, MR and USG of the brain, the arrangement of anti-epileptic therapy and basic immunological examination were made during the first year of investigation. Still, after the stabilisation of anti-epileptic therapy (monitoring) and indicated immunomodulatory therapy was added. RESULTS: The immunologic examination was negative in 4 patients, all being members of GENKONV group. Atopy was found in 56% of GK group, and in 65% of PK group. Disturbances of specific cellular immunity were revealed in 80% of the patients of the GK group, and in 85% of PK group. The signs of inflammatory activity and other signs of allergy were present to a lesser extent. CONCLUSIONS: Out of the amount of 125 patients only 3.2% yielded no disturbances of immunity. The application of immunomodulatory therapy appears to represent a promising supplementary-stabilisation therapy. (Tab. 2, Fig. 4, Ref. 5.)

[Immunomodulatory therapy of epilepsy with transfer factor]. / Imunomodulacná terapia epilepsie transferovým faktorom.

Effect of immunotherapy with Transfer factor administered for a period of three months was studied in a group of ten epileptic patients, treated with carbamazepine or primidon previously and throughout the study. Out of eight patients, who finished the study we could notice significant reduction of epileptic discharges in eight patients. The results of this study prove that addition of immunomodulatory treatment to patients with intractable epilepsy could substantially improve the course of the disease in some patients. (Tab. 1, Fig. 5, Ref. 13.)

Increase in magnesium plasma level after orally administered trimagnesium dicitrate.

Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.

Tubular basement membrane thickening in diabetes mellitus.

Authors measured the thickness of the basement membranes of the proximal and distal tubuli in the renal cortex in 20 patients with verified diabetes mellitus. The test group consisted of 20 patients with small abnormalities of glomeruli (or in the range of variable norm), of the same sex and comparable age. Measurements were performed in locations without tubulo-interstitial changes. The average thickness of TBM in patients with diabetes mellitus was 1540 +/- 616 nm, and in the test group 360 +/- 86 nm, which is a statistically significant difference (p < 0.000000). In spite of the small number of cases and possible error in the manual measurement of electron microscopic pictures, a significant thickening of TBM in diabetes mellitus has been found. We consider this to be of diagnostic value.

[Variations in histologic and ultrastructural findings in renal glomerular biopsies]. / Rozdielne histologické a ultrastruktúrne nálezy v glomeruloch renálnej biopsie.

On the basis of 506 renal biopsies performed within a six-year period (237 of which were evaluated electron-microscopically) the authors discovered that in 11 cases the diagnosis based on electron microscopic examination had to be corrected or supplemented by the diagnostic statement of membranous glomerulonephritis. These cases included 1 boy (HBsAg positive), 2 men and 8 women were middle aged. 5 women were treated due to polyarthritis. All cases when examined light-microscopically yielded a pattern evaluated as normal, or as minute abnormalities of glomeruli. Half-thick sections were not sufficient for the diagnosis. 3 cases of biopsies yielded a variously developed chronic tubulointerstitial nephritis, two cases were accompanied with polyarthritis. On the basis of the latter the authors consider the electron microscopic examination as indicated: 1. in cases when the diagnosis statement is not achieved by other examinations, 2. findings are in the range of the so-called variable norm, 3. in all cases of minute abnormalities in glomeruli detected without electron microscopy, 4. the impact of any of effective drugs cannot be excluded, 5. the diagnostic conclusion based on renal biopsy and the clinical-laboratory pattern of the disease are inconsistent. The authors assume that especially the fourth and fifth groups are going to be gradually supplemented and made more precise. (Fig. 1, Ref. 5.).

Investigation of immunotoxicity of supercypermethrin forte in the Wistar rat.

The study was done to find out whether subacute exposure to supercypermethrin forte (SCM) affected cellular and humoral immunity. Groups of 10 male Wistar rats were given SCM by gavage for 28 days at 12.5 mg kg-1 day-1 (1/14 LD50), 8.75 mg kg-1 day-1 (1/20 LD50) and 4.38 mg kg-1 day-1 (1/40 LD50) and the response of splenocytes to mitogens, natural killer cell activity, plaque forming cell assay and phagocytosis were examined. The response of splenocytes to the mitogens phytohaemagglutin and concanavalin A, and to a T-dependent antigen (sheep red blood cells), was enhanced at 1/40 LD50 SCM, and at 1/20 and 1/14 LD50 these variables were suppressed. In the group exposed to 1/14 LD40 SCM the suppression was statistically significant. A non significant but dose-related increase in NK-cell activity was observed. The phagocytic activity of polymorphes was not significantly affected. Thus, SCM at 1/14 LD50 had significant adverse effects on a number of immunological functions in rats, but lower doses had no effect on these activities.

[Minor glomerular abnormalities in chronic tubulointerstitial nephritis]. / Malé abnormality glomerulov pri chronických tubulointersticiálnych nefritídach.

The authors examined consecutive renal biopsies from 43 patients with minor glomerular abnormalities and from 35 patients with chronic tubulointerstitial nephritis (in the least affected glomeruli). The findings were evaluated according to WHO criteria of minor abnormalities. They found that significantly more frequently lipid drops were found in minor abnormalities (6:0), as well as changes in the capillaries of glomeruli (breakdown 1:7), wrinkling (15:29-highly significant even after correction of p)) in tubulointerstitial nephritis. The incidence in another 15 compared indicators there was not significantly different. With regard to the assembled results the authors consider the morphological finding of minor glomerular abnormalities as non-specific changes, and adaptational glomerular changes in response to various noxious substances. Therefore it is necessary to evaluate purely morphological findings of minor abnormalities carefully and in a differentiated manner, in particular in conjunction with treatment.

Comparative effects of a Mg-enriched diet and different orally administered magnesium oxide preparations on ionized Mg, Mg metabolism and electrolytes in serum of human volunteers.

OBJECTIVE: To determine whether: 1) short-term dietary elevation in magnesium (Mg) intake could alter serum ionized Mg (IMg2+), total Mg (TMg); % ionized Mg (% IMg2+) and other cations; and 2) different formulated preparations of Mg oxide (MgO) in the presence and absence of phosphate could alter serum IMg2+, TMg, % IMg2+ and other cations in Mg-loaded subjects. METHODS: A randomized, triple cross-over study was performed on a rigorously defined group of normal male volunteers. Eighteen males were administered diets containing four to five times the United States recommended daily allowance (USRDA) of Mg followed by a randomization of three different MgO preparations, in the presence or absence of phosphate, containing equimolar amounts (12.34 mmol) of elemental Mg. Forty age-matched volunteers served as reference range controls. Specific ion selective electrodes were utilized to measure IMg2+, ionized calcium (ICa2+), sodium (Na+) potassium (K+) and hydrogen ion concentration (H+). Measurement of urinary excretion of Mg as well as TMg were determined by atomic absorption spectroscopy. RESULTS: Diets enriched with different oral formulations of Mg given for 6 days result in significant elevations in serum IMg2+ and % IMg2+ but not TMg, ICa2+, K+ or H+ in normal subjects. Although such Mg-loaded subjects demonstrate significant elevation in urinary excretion of Mg, no further changes in IMg2+, TMg or any of the serum cations were produced by ingestion of either of the three MgO preparations. Subjects showing normally low basal levels of serum IMg2+, (< or = 0.54 mM/L), could easily have their serum IMg2+ level manipulated by diets enriched with Mg, whereas subjects having average normal or high normal IMg2+ levels did not have their IMg2+ elevated significantly with either diets enriched with Mg or with exogenous MgO. CONCLUSION: These results indicate that since serum IMg2+ and % IMg2+, but not TMg, can be altered by dietary intake, previous or future findings which may indicate no change in TMg by diet may not reflect changes in biologically-active Mg.

Amphiphilic detergents inhibit production of IgG and IgM by human peripheral blood mononuclear cells.

All types (cationic, anionic and non-ionic) amphiphilic detergents significantly inhibited the production of both IgG and IgM by human peripheral blood mononuclear cells after polyclonal activation in vitro. The most potent inhibitors were didodecyldimethylammonium bromide (DDAB) and (1-methyldodecyl)dimethylamine N-oxide (2-ATDNO). They were able to suppress effectively the immunoglobulin production in 10(-3)-10(-8) M concentrations. A medium inhibitory effect was observed with Slovapon, sodium dodecyl sulphate (SDS) and Triton X-100, while Slovanik showed an inhibition only in concentrations higher than 10(-2)%. These results suggest that amphiphilic detergents may be characterized as potential immunotoxic substances with very negative effects on the immunoglobulin production.

Neuroleptics and the immune system.

The authors investigated immunological parameters during treatment with risperidone and recorded a reduction of IgG and IgM after 24 weeks of treatment. With this finding corresponded a reduced IgG synthesis, but not IgM synthesis, investigated in vitro. It was thus revealed that risperidone does not exert an immunological effect. In the course of treatment changes of immune parameters were recorded which can be, however, explained by immunological aspects of the course of the disease. The role of the antagonist of 5HT receptors is very complicated and cannot be explained by a single mechanism.

[Treatment of nephrotic syndrome with cyclosporin A]. / Liecba nefrotického syndrómu cyklosporínom A.

The authors treated eight children with corticoid dependent syndrome caused by minor abnormalities of the glomeruli with Cyclosporin A. They administered Cyclosporin, 5 mg/kg/24 h., for a period of 8-16 weeks. In three patients they used Cyclosporin A alone, 5 children were given in addition 10 mg Prednisone per day. They achieved complete remission in all patients. During treatment they monitored haematological and biochemical parameters as well as Cyclosporin A levels; before treatment and after its termination they examined also immunological indicators. They did not observe any serious side effects of treatment.

[Selected immunologic indicators in malignant bone tumors]. / Vybrané imunologické ukazatele pri kostních maligných nádoroch.

In patients with the malignant tumor of bone (17 osteosarcomas, 8 Ewing tumors) longterm observations were made, and namely at the beginning of the disease, after the surgical removal of the tumor, during chemotherapy and in the terminal phase of the disease. The observations concentrated on the following selected immunology parameters: active lymphocytes T, lymphocytes T, lymphocytes B, large granular lymphocytes, IgG, IgA, IgM and circulating immune complexes. In non-treated patients prior to diagnosing the disease, reduction of active lymphocytes T was found out while the total lymphocytes T remained unchanged. However, no significant differences were found out between benign and malignant tumors. The surgical removal of the tumor results in the change in imunologic indicators, the increase of active lyphocytes T, lymphocytes T and the decrease in the circulating immune complexes. The change is of temporary nature, the subsequent deterioration is caused by both the progression of the disease and chemotherapy. The values of immunoglobulins and lymphocytes B fluctuated during the whole course of the disease in physiological levels. The observation of active lymphocytes T and lymphocytes T can be used for monitoring of the immunosuppression in cytostatic treatment. The levl of IgG is differentially diagnostically used to distinguish between the tumor and inflammatory processes.

[The development of cytotoxic T lymphocytes in HLA-D/DR identity]. / Vznik cytotoxických lymfocytov T pri identite HLA-D/DR.

The development of cytotoxic T-lymphocytes is controlled by genes of the HLA complex and occurs, in the majority of cases, when the responding and stimulating subjects differ both in HLA-A, -B and HLA-D/DR antigens. We examined a married couple for kidney transplantation and found that they differed in HLA-A, -B antigens and were identical in HLA-DR antigens. The negative results of the MLC test confirmed the serological findings. Nevertheless, cytotoxic T-lymphocytes developed despite HLA-D/DR identity. The presented case is one of the few published exceptions to the rule governing the development of cytotoxic T-lymphocytes.

HLA-D/DR identity results in a positive CML reaction.

Investigating HLA-A, HLA-B, HLA-C, and HLA-DR antigens, MLR, CML, and PLT reactivity in two unrelated persons it was found that despite their HLA-D/DR identity cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the necessary proliferative impetus for the generation of CTL.

HLA-DP antigens provide the proliferative impetus for the generation of cytotoxic T lymphocytes.

Investigating HLA-A, -B, -C, -DR and -Dw antigens and MLR, CML, and PLT reactivity in two unrelated persons, it was found that, despite their HLA-D/DR identity, cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the proliferative impetus for the generation of CTL.

The importance of immunohistochemical examination of glomerulonephritis.

There were 942 cases of glomerulonephritis classified according to WHO out of 1499 renal biopsies. Immunoglobulins IgG, IgA, IgM, C3 and fibrinogen were examined immunohistochemically in a standard way and IgD, IgE, albumin, C4 and HBsAg in a non-standard way. The results were compared with a control group. The results show that the excluding value of the negative immunohistochemical examination in glomerulonephritis is higher than the proving value of the positive examination.