Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models.

2,4,6-Trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C and stimulates apoptosis; however, in smooth muscle cells it may increase the perfusion pressure. The main aim of the present study was to evaluate the physiological effect of direct stimulation of phospholipase C on vascular smooth muscle reactivity using three contraction models. Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in the present model was measured by an increased level of perfusion pressure with a constant flow. Concentration-response curves (CRCs) obtained for phenylephrine, arg-vasopressin, mastoparan-7 and Bay K8644 presented a sigmoidal association. In comparison to the control curves, CRCs in the presence of m-3M3FBS were significantly shifted to the left except for Bay K8644. Analyses of calcium influx suggest that in the presence of m-3M3FBS the calcium influx from intra- and extracellular calcium stores was significantly higher. The results of the present experiments suggest that m-3M3FBS significantly increases the reactivity of vascular smooth muscle stimulated with metabotropic receptors or G-protein by an increase in calcium influx from intra- and extracellular calcium stores. The current knowledge regarding the apoptotic pathway shows the significance of calcium ions involved in this process, thus, m-3M3FBS may induce apoptosis by an increase of cytoplasmic calcium concentration; however, simultaneously, the use of this mechanism in therapy must be preceded by a molecular modification that eliminates a possible vasoconstriction effect.

Cyclosporine-A, but not tacrolimus significantly increases reactivity of vascular smooth muscle cells.

BACKGROUND: Application of cyclosporine-A (CsA) or tacrolimus is associated with numerous side effects. One of the main reasons for restricting usage of CsA is hypertension. In tacrolimus treated subjects the frequency of these phenomena is significantly lower. The known molecular mechanism of action of tacrolimus and cyclosporine-A seems to be the same, thus we decided to compare modulatory effect of drugs on vascular smooth muscle contractility. METHODS: Experiments were performed on isolated and perfused tail artery of Wistar rats. Contraction force was measured by increased degree of perfusion pressure with a constant flow rate. RESULTS: Concentration-response curves for agonist in the presence CsA were significantly shifted to the left with increase in maximal responses. This effect was due to increased calcium influx from extracellular calcium stores whereas there were no significant changes in calcium influx in the presence of tacrolimus; concentration-response curve was comparable to controls. CONCLUSION: Our results strongly support the idea that main difference between effects on smooth muscle contractility of calcineurin-dependent immunosuppressants: CsA and tacrolimus is related to the different level of extracellular calcium influx to the cytoplasm. The elucidation of these mechanisms may permit the identification of new therapeutic strategies against CsA-induced hypertension.

[Adverse reactions after vaccination against influenza in chronically ill people]. / Objawy niepozadane u przewlekle chorych po szczepieniu przeciwko grypie.

The objective was to assess the early and late adverse reactions after vaccination against influenza with the help of SmithKline Beecham's Fluarix vaccine in chronically ill people. 1010 people was selected to undergo vaccination. These included 621 woman aged average 44.2 and 389 men aged average 48.2. The vaccination was conducted simultaneously and the period of monitoring adverse reactions lasted 9 months. The vaccination was done in accordance with recommendations of manufacturer. All the vaccinated people suffered from circulatory system disorders, bone system disorders, mental disorders and endocrinological problems, during the vaccination they were in period of remission. The observed early symptoms fell into two categories: local and general. The late adverse reaction assessed with appearance of aggravation of main chronic disease or with appearance of the new chronic disease. The local symptoms included swelling, reddening and pain in the vaccinated area. 67 people (6.6%) reported swelling, 85 (8.4%) reported reddening, 12 people (1.2%) reported pain in the vaccinated area. The general symptoms included headache, bad mood and temperature over 37.5 degrees C. 19 people (1.9%) reported bad mood, 10 people (1%)--headache and 8 people (0.8%) reported temperature over 37.5 degrees C. Coexistence of two or three types of symptoms was present in 15 cases (1.5%). There were no late adverse reactions in the study group. The low percentage of early adverse reactions and no late adverse reactions encourages a wider use of vaccines against influenza in chronically ill people.