Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.     

Interleukin-1 alpha, soluble interleukin-2 receptor, and IgG concentrations in cystic fibrosis treated with prednisolone

The cytokines interleukin-1 and interleukin-2 participate in the inflammatory response, and may contribute to hypergammaglobulinaemia G and the development of lung injury in cystic fibrosis. Anti-inflammatory treatment with corticosteroids may attenuate this response. The effect of a 12 week course of oral prednisolone on spirometry and serum concentrations of interleukin-1 alpha (IL-1 alpha), soluble interleukin-2 receptor (sIL-2R), and IgG was investigated in 24 children with cystic fibrosis. Prednisolone was administered, in a double blind and placebo controlled manner, at an initial dose of 2 mg/kg daily for 14 days and tapered to 1 mg/kg on alternate days for 10 weeks. The treated group (n = 12) experienced an increase in forced expiratory volume in one second and forced vital capacity at 14 days, however, these changes were smaller at 12 weeks. In the treated group, change in pulmonary function was associated with decreased serum IgG and cytokine concentrations. Prednisolone suppresses serum concentrations of these cytokines, which may participate in the inflammatory response, the excessive synthesis of IgG, and airflow obstruction observed in cystic fibrosis patients.     

A seroepidemiological study of toxoplasma gondii infection in children of northern Greece

The aims of this study were to determine the incidence of toxoplasmosis in children ofthe northern Greece region through the evaluation of serologic examination. Sera of 486 children, aged between 6 months and 15 years, suffering from different clinical entities, were tested for anti-Toxoplasma gondii specific IgG antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a high percentage (11.1 percent) of the hospitalized children reacted positively to this method. Males and females had equal prevalence, 11 percent and 11.2 percent, respectively. Seropositivity rate was higher in children aged between 6 and 10 years old. In conclusion, our results indicate toxoplasma infection is an important public health problem affecting children and adolescents in northern Greece. We believe that the study described here could be considered for inclusion in existing national screening programs for hospitalized children.     

Blood volume regulation during hemodialysis

Hemodialysis (HD)-induced hypotension may be precipitated by severe hypovolemia. To avoid the appearance of destabilizing hypovolemias, we have developed a biofeedback control system for intradialytic blood volume (BV)-changes modeling. The system, incorporated in a dialysis machine, is based on a multivariable closed-loop control with a dependent output variable, the BV changes, and two independent control variables, the ultrafiltration rate (Qf) and dialysate conductivity (DC). The relative BV changes occurring during HD are measured by an optical device. The Qf and DC are continuously adjusted by the control model during the treatment to minimize any discrepancies between the ideal targets for the BV, the patient's body weight reductions, and the experimentally obtained results. The system manages three kinds of errors: in BV changes, the total weight loss, and the sodium balance. The latter is controlled by a dedicated kinetic model that continuously calculates the equivalent DC and, by the end of the session, tends to make the sodium balance the same as the one obtained in conventional HD with constant DC. This system's capacity to improve intradialytic hemodynamic tolerance has been assessed in a crossover study of eight highly symptomatic patients. Conventional HD (CHD; period A) was compared with blood volume-controlled dialysis sessions (BV-CHD; period B) following a protocol with an A1-B-A2 sequence, with each period lasting 1 month. A lower decrease in BV (-10.6%) was obtained during BV-CHD (period B) compared with CHD (-12.3% in period A1 and -12.5% in period A2). The predialysis to postdialysis systolic arterial pressure changes were lower in period B (-12.4%) than in period A (-20% in A1 and -17.5% in A2; P < 0.05) despite similar total Qf and mean treatment times. A significant reduction in the number of severe hypotensive episodes (three in period B v 26 in period A1 and 16 in period A2; P < 0.05) and the overall incidence of complaints, especially of muscular cramps, was found in BV-CHD. These results were reflected in a reduced need for therapeutically administered isotonic saline in each session (60 mL in B v160 mL in A1 and 95 mL in A2; P < 0.05). In conclusion, the proposed biofeedback system for intradialytic BV control may be useful to avoid severe hypovolemic states, to stabilize BV by modeling its trend, and to avoid reaching individual critical BV thresholds in hypotension-prone patients.     

Peripheral α2-adrenoceptor-mediated sympathoinhibitory effects of mivazerol

Summary— Mivazerol is a new compound that could potentially reduce perioperative cardiovascular morbidity and mortality in patients with or at risk of coronary disease and submitted to surgery. This action of mivazerol depends on a well documented centrally mediated reduction in sympathetic nerve activity, but a direct peripheral decrease in sympathetic neurotransmitter release induced by activation of prejunctional α₂-adrenoceptors located on sympathetic nerve endings could also contribute. To investigate this issue, the effects of mivazerol on the pressor, systemic and regional hemodynamic (pulsed Doppler technique) as well as on the cardiac responses to electrical stimulation of the spinal cord (SCS) were measured in pithed rats in the absence and in the presence of mivazerol. Mivazerol exerted strong sympathoinhibitory effects: SCS-induced increases in blood pressure, total peripheral resistance and heart rate were dose-dependently reduced by mivazerol, but among the regional vascular beds investigated, only the hindlimb vasoconstrictor responses were significantly drug-affected. All these sympathoinhibitory effects of mivazerol were abolished by prior yohimbine administration. Simultaneously, mivazerol did not induce any postjunctional adrenoceptor blockade as it did not affect noradrenaline cardiac and hemodynamic effects. On the contrary, through postjunctional α₂-adrenoceptor stimulation, mivazerol, in this pithed preparation, dose-dependently increased blood pressure, total peripheral and hindlimb vascular resistances, but heart rate was not affected. We conclude that, in the pithed rat, mivazerol exerts strong peripheral sympathoinhibitory effects. The mechanism involved is prejunctional α₂-adrenoceptor activation as i) mivazerol does not display any postsynaptic α-adrenoceptor blocking effect — it even behaves as a postsynaptic α₂-adrenoceptor agonist — and ii) yohimbine abolishes mivazerol's sympathoinhibitory effects. Thus, direct peripheral together with central mechanisms contribute to mivazerol's sympathoinhibitory effects and ultimately to its cardioprotective action.     

Erythrocytes-mediated metabolic activation of cyclophosphamide in yeast mutagenicity test

The degree of conversion of cyclophosphamide (CP) into mutagenic intermediates was studied using mouse erythrocytes as the metabolic activation system. The amount of mutagenic intermediates produced was measured indirectly in terms of induced frequencies of mitotic recombination, mitotic gene conversion, and reverse mutation in the diploid D7 strain of Saccharomyces cerevisiae. In the absence of S9 microsomal fraction or erythrocytes, CP did not induce any genetic response. In the presence of erythrocytes, on the other hand, CP clearly induced increases in the three genetic endpoints. The responses, however, were lower than those observed with the S9 activation system. The activating principle seems to be the oxyhemoglobin. In fact, neither p-nitroanisole O-demethylase activity nor genotoxic responses performed with red-blood cells from uninduced and PB-induced mice indicate that (possible) water-soluble forms of cytochrome P-450 were responsible for the activation of CP by erythrocytes.