The aim of the studies was to ascertain if adenosine is able to co-operate with selected hematopoietic growth factors and cytokines, namely with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), interleukin-3 (IL-3), and interleukin-11 (IL-11), in inducing the growth of colonies from hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) from normal bone marrow cells in vitro. Adenosine was found not to produce any colonies when present in the cultures as the only potential stimulator. All the tested cytokines and growth factors were observed to induce the growth of distinct numbers of GM-CFC colonies, with the exception of IL-11. When suboptimal concentrations of the evaluated cytokines and growth factors were tested in the cultures in which various concentrations of adenosine were concomitantly present, mutually potentiating effects were found in the case of IL-3 and SCF. These results confirm the role of adenosine in regulation of granulopoiesis and predict IL-3 and SCF as candidates for further in vivo studies of their combined administration with adenosine.
Endothelin-1 (ET-1) acts on ETA and ETB receptors and has been implicated in hemorrhagic shock (shock). We determined effect of shock and resuscitation by hypertonic saline (saline) or centhaquin on ETA and ETB receptor expression. Rats were anesthetized, a pressure catheter was placed in the left femoral artery; blood was withdrawn from the right femoral artery to bring mean arterial pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min later sacrificed to collect samples for biochemical estimations. Resuscitation with centhaquin decreased blood lactate and increased MAP. Protein levels of ETA or ETB receptor were unaltered in the brain, heart, lung and liver following shock or resuscitation. In the abdominal aorta, shock produced an increase (140 %) in ETA expression which was attenuated by saline and centhaquin; ETB expression was unaltered following shock but was increased (79 %) by centhaquin. In renal medulla, ETA expression was unaltered following shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %) in ETB expression which was completely attenuated by centhaquin and not saline. Shock induced changes in ETA and ETB receptors in the aorta and renal medulla are reversed by centhaquin and may be contributing to its efficacy., S. Briyal, R. Gandhakwala, M. Khan, M. S. Lavhale, A. Gulati., and Seznam literatury
The objective of the present report was to clarify the postoperative stress response of some inflammatory markers, namely of proinflammatory cytokines and leptin levels during uncomplicated postoperative periods. The results were compared with the dynamics of these parameters during intraabdominal sepsis. We followed 20 patients after a planned resection of colorectal cancer in stage Ib-IV with uncomplicated healing and 13 obese men after laparoscopic non-
adjustable gastric banding. These were compared to 12 patients with proven postoperative sepsis. The control group consisted of 18 healthy men. The observed parameters included serum levels of cytokines, tumor necrosis factor-α(TNFα), interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, soluble receptor of interleukin-2 (sIL-2R) and leptin. It was found that during the first 24 h after resection there was a significant increase in the serum concentration of IL-6 up to 1125±240 ng/l, which declined within the next 48-72 h. Serum concentration of TNF α was
highest 18-24 h after resection (205±22 ng/l) and after banding (184±77 ng/l). IL-1β had a stable serum concentration without significant elevation. Serum concentration of IL-8 after resection rose to 520±200 ng/l after 36-48 h. Maximal cytokine levels after gastric banding were quantitatively lower (IL-6 414±240 ng/l, TNFα 184±77 ng/l) than after resection. We found significant elevation of plasma leptin concentration (32±10 ng/ml) 24 h after banding compared with preoperative values (18±5 ng/ml, p<0.05). Leptin levels 48 and 72 h after banding rapidly returned to the level before operation. During abdominal surgery leptin shows to be an acute phase reactant. Proinflammatory cytokines can be main regulatory factors of leptin during this period. Significant correlation between leptin and TNFα (similarly
demonstrated by other authors in models of bacterial inflammation) indicates that TNFα can be the crucial regulator of leptin generation in the early postoperative period. On the basis of our results we recommend to observe IL-6 and IL-8 at 24-72 h after the surgery in patients with a high risk of early postoperative septic complications.