Barbara Tejza

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.

Phenotype of NK Cells Determined on the Basis of Selected Immunological Parameters in Children Treated due to Acute Lymphoblastic Leukemia.

AbstractAcute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. The chemotherapy for ALL is associated with a profound secondary immune deficiency.We evaluated the number and phenotype of natural killer (NK) cells at diagnosis, after the intensive chemotherapy and following the completion of the entire treatment for patients with ALL. The fraction, absolute number, and percentage of NK cells expressing interferon-&ggr; were determined in full blood samples. The fraction of NK cells expressing CD158a, CD158b, perforin, A, B, and K granzymes was examined in isolated NK cells.We have shown that patients assessed at ALL diagnosis showed significantly lower values of the fraction of NK cells and percentage of NK cells with the granzyme A expression. Additionally, the absolute number of NK cells, the expression of CD158a, CD158b, perforin, and granzyme A were significantly lower in patients who completed intensive chemotherapy. Also, there was a significantly higher fraction of NK cells expressing granzyme K in patients who completed the therapy.Abnormalities of NK cells were found at all stages of the treatment; however, the most pronounced changes were found at the end of intensive chemotherapy.

2,4,6‑Trimethyl‑N‑[3‑(trifluoromethyl)phenyl]benzenesulfonamide increases calcium influx in lipopolisaccharide-pre-treated arteries

It has been demonstrated that 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C (PLC) and stimulates apoptosis in smooth muscle cells, which may increase vascular reactivity. The primary aim of the present study was to evaluate the physiological effects of the direct stimulation of PLC by m-3M3FBS on vascular smooth muscle reactivity in arteries pre-treated with lipopolysaccharides (LPS) as a model of septic shock. Experiments were performed on isolated and perfused tail arteries of Wistar rats. The contraction force in the model was measured by assessing increases in perfusion pressure at a constant flow. Parameters describing the concentration-response curves (CRCs) obtained for phenylephrine and arginine-vasopressin in the presence of LPS confirmed a decrease in vessels reactivity. In comparison with the controls, m-3M3FBS treatment caused a significant increase in LPS-untreated as well as pre-treated arteries. Furthermore, in the presence of m-3M3FBS, calcium influx from intra- as well as extracellular calcium stores was significantly higher for LPS-untreated and pre-treated arteries. The results of the present study suggested that m-3M3FBS significantly increased the reactivity of vascular smooth muscle cells pre-treated with LPS by increasing the calcium influx from intra- and extracellular calcium stores. Further studies investigating this mechanism are required to evaluate whether this pathway may be a potential therapeutic strategy to treat sepsis.

EFFECT OF PHOSPHOLIPASE C INHIBITION ON VASCULAR SMOOTH MUSCLE CONTRACTION

Phospholipase C is the key enzyme responsible for the hydrolysis of membrane phospholipids phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to two intracellular transmitters - diacylglycerol (DAG) and inositol triphosphate (IP 3 ). PLC activation of smooth muscle leads to an increase in the concentration of IP 3 and DAG which initiates the increase in the concentration of calcium ions into the cytoplasm as a result of the flow from the intracellular and then from extracellular pool. Main aim of this study was to evaluate the effect of PLC inhibitor U-73122 on vascular smooth muscle contraction stimulated pharmacologically with phenylephrine (PHE, α 1 -adrenoceptor agonist) and arg-vasopressin (AVP, vasopressin receptor agonist). Material and methods. Experiments were performed on isolated and perfused tail artery of Wistar rats. Contraction force in our model was measured by increased level of perfusion pressure with a constant flow. Results. Reactivity of vascular smooth muscle cells to PHE (10 -9 - 10 -3 M/L), and AVP (10 -10 – 10 -4 M/L), in the control group and in the presence of U-73122 – phospholipase C inhibitor at concentrations 1, 3 and 10 μM/l was analyzed. EC 50 values calculated for PHE and AVP were 7.52 (±0.97) x10 -8 M/L and 1.84 (±0.6) x10 -8 M/L, respectively. The concentration-response curves obtained for PHE and AVP in the presence of U-73122 were shifted to the rightward with a decrease in maximal responses. In the presence of U-73122 the significant and dose dependent reduction in perfusion pressure was found for both agonists for calcium influx from intracellular calcium stores and from extracellular space. Conclusion. Results of our experiments suggest that in the presence of phospholipase C inhibitors, contraction induced by G-protein coupled receptors activation may by effectively inhibited by reduction in calcium influx from intra and extracellular calcium stores.

Niedożywienie u dzieci z chorobą nowotworową

Streszczenie Zaburzenia odzywienia nalezą do czestych objawow choroby nowotworowej. Rozwoj niedozywienia w przewleklej chorobie jest wynikiem zaburzonej rownowagi energetycznej ustroju, w ktorym zwiekszone zapotrzebowanie na skladniki odzywcze nie jest pokrywane z powodu mniejszej podazy i zwiekszonej utraty. Mechanizm rozwoju niedozywienia jest zlozony i nie do konca poznany, zalezy od czynnikow produkowanych przez tkanke nowotworową, jak i uklad immunologiczny gospodarza. Zastosowanie nowoczesnego, skojarzonego leczenia onkologicznego daje wyzsze wskaźniki wyleczen, ale wiąze sie z wiekszym ryzykiem wystąpienia skutkow ubocznych, w tym zaburzen stanu odzywienia. Dzieci z chorobą nowotworową nalezą do grupy wysokiego ryzyka utraty masy ciala i postepującego niedozywienia w toku leczenia onkologicznego. Jest wiele doniesien o gorszej tolerancji chemioterapii, wzroście powiklan infekcyjnych i wiekszej śmiertelności u pacjentow z niedozywieniem. Badanie stanu odzywienia powinno nalezec do standardu badania podmiotowego i przedmiotowego. Badania przesiewowe opierają sie na wywiadzie, pomiarach antropometrycznych i badaniach laboratoryjnych, a ich celem jest określenie stopnia niedozywienia i w razie konieczności wlączenie leczenia zywieniowego. W pracy tej przedstawiono kryteria sluzące do oceny stanu odzywienia i momentu wlączenia leczenia zywieniowego oraz zakres niezbednych badan laboratoryjnych. Wedlug tych zalecen, jak i innych doniesien z literatury, preferuje sie stosowanie zywienia dojelitowego wszedzie tam, gdzie jest to mozliwe, jako bardziej fizjologicznego i dającego mniej powiklan.

Trudności diagnostyczne w przypadku gruźliczego zapalenia otrzewnej – opis przypadku

Przedstawiono opis przypadku gruźlicy jamy brzusznej u 11-letniego chlopca, u ktorego rozpoznanie zostalo ustalone na podstawie badania histopatologicznego materialu pobranego podczas laparoskopii.