Effect of exercise on plasma atrial natriuretic factor and cardiac function in men and women

In order to provide an integrated view of the physiology of atrial natriuretic factor (ANF) during exercise, we studied changes of its plasma concentrations in 13 normal subjects (seven males, six females) during three graded exercise levels and two periods of recovery (5 and 30 min), concomitantly with an assessment of cardiac function and ventricular volumes by multigated radionuclide angiography. Mean ANF levels (+/- SEM) increased in all patients at the second (P less than 0.002) and third (P less than 0.002) exercise levels, and after 5-min recovery (P less than 0.01): in males from 16 +/- 7 to 30 +/- 11 pg ml-1 at the third level, in females from 27 +/- 12 to 61 +/- 33 pg ml-1. Normal values were observed after 30-min recovery. Even if mean ANF levels were all higher in females, this difference did not reach statistical significance (P = 0.06). Significant decreases of ventricular volumes, as well as increases of ejection fraction and rate pressure product, were noted during exercise and were similar in both sexes. The kinetics of plasma ANF concentrations, compared with the increase of rate pressure product, was characterized by a latency and a remanence in recovery. This remanence, also present in the changes of ventricular volumes, supports the hypothesis that other factor(s) like catecholamines might still exert their influence after the exercise stops.     

A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin

Although the chemical structures of the antidepressants mirtazapine and mianserin are closely related there are considerable differences in their biological properties. To find an explanation of this, various physicochemical properties of mirtazapine and mianserin were measured or calculated. Isosteric replacement of CH in mianserin by N in mirtazapine has profound effects on physicochemical properties. The charge distributions as indicated by NMR and calculated by semi-empirical quantum mechanics differ, not only for the changed aromatic A-ring (as expected), but also in other regions of the molecule. The N5 atom in particular, which is conjugated to the changed aromatic ring, is less negatively charged in mirtazapine than in mianserin. Consequently the oxidation potential of mirtazapine is significantly higher than that of mianserin. Another result of this difference in charge distribution is that the (calculated) dipole-moment vectors of the compounds are oriented roughly perpendicular to each other. The dipole moment of mirtazapine is, moreover, three times larger than that of mianserin; mirtazapine is, therefore, more polar than mianserin and this is reflected in a lower retention index. Finally, the basicity of mirtazapine, expressed as the pK_a value, is slightly but significantly lower than that of mianserin. The observed differences between the physicochemical properties of mirtazapine and mianserin result in different interactions of these two antidepressants with macromolecules, such as receptors, transporters and metabolizing enzymes; this might explain the differences observed in pharmacological activity and metabolic and kinetic behaviour, that is, the reduced affinity for the α₁-adrenoceptor and negligible noradrenaline reuptake of mirtazapine compared with mianserin.     

Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC)

Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28^? phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8⁺ CD28^? T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8⁺ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8⁺ CD28⁺ and CD8⁺ CD28^? T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8⁺ CD28^? cells became enriched after co-culturing T cells with iEC cell lines and primary iEC. Induction of the CD8⁺ CD28^? phenotype in cord blood and adult T cells was observed in co-cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down-modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined results suggest that CD8⁺ CD28^? T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8⁺ CD28^? T cells in the iIEL compartment.     

Immunomodulation by hydatid cyst fluid toxin (Echinococcus granulosus)

Since the experimental infection by hydatid cysts ( Echinococcus granulosus ) in mice causes immunomodulation of the host, the effects of hydatid fluid (HF) and fractions of HF were compared in vitro and in vivo . Fractions of HF were obtained using ammonium sulphate precipitation, chloroform/methanol extraction and thin-layer chromatography (TLC). HF proved to be toxic to murine peritoneal macrophages in vitro , and when macrophages were incubated with the different fractions of HF, most toxicity was found in a single TLC-purified fraction with an adjuvant-like effect on the production of specific antibodies against bovine albumin and human red blood cells in mice. Treatment of mice with the toxin caused a drop in the percentage of peripheral blood lymphocytes. Flow-cytometric analysis showed that T-cells from toxin-treated mice had lower membrane-CD3, CD4 and CD8 density, and had higher percentages of CD8⁺ splenocytes and CD4⁺ thymocytes expressing CD25. The toxin caused a down-regulation of CD4 and CD8 expression on thymocytes in vitro , that was dependent on the presence of macrophages. The results may attribute to these toxins a role in the host-parasite relationship of hydatidosis.     

The decay of house dust mite allergens, Der p I and Der p II, under natural conditions

Background: Fluctuations in the level of mite allergens in domestic house dust are the result of changes in the balance between synthesis, removal and decay. Purely physical forces as well as enzymatic degradation, mediated by house dust inhabiting microbes, may contribute to the decay of allergens in domestic dust. Knowledge about the speed of decay is essential for an understanding of the dynamics of allergen levels. Objective: The present study is a quantitative assessment of the speed of decay at nine combinations of temperature (15°C, 20°C and 25°C) and relative humidity (33%, 55% and 75%). Methods: Samples of mite infested material of an old rug were stored at these temperature/relative humidity-combinations for 6, 12 or 18 months, after the mites were killed by cither a freezing treatment or an acaricide (lindane). The microbes living in the rug presumably survive these treatments. Concentrations of Der p I and Der p II + Der f II. in extracts of the rug material, were measured by a radio immunoassay. Results: No significant changes in the levels of Der p I and Der p II +Der f II, could be detected even after 1¹/₂ year at a high temperature and humidity. Conclusion: These findings incidate that mite allergens can be extremely stable under normal domestic circumstances.     

Influence of Electromagnetic Fields on Function of Automated External Defibrillators

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false‐positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus. Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence‐randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure. Results: Of 760 tests run, 18 (2.37%) cases of false‐positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields. Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.