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M Durlik

Publications and source records attributed to M Durlik.

At least 73 records · Page 4Linked to original sources

Surgical trauma evokes a rise in the frequency of hematopoietic progenitor cells and cytokine levels in blood circulation.

Alterations in the mononuclear cell populations in the blood circulation are among the most characteristic changes after surgical trauma. They reflect changes in the hematopoietic compartment which develop following surgery. The process of mobilization and differentiation of the hematopoietic population is regulated by cytokines known as growth factors for stem and progenitor cells (SCF, IL-1, IL-3, IL-6, IL-1L, TNF, CSFs). Our question was whether operative trauma resulted in the release of the hematopoietic progenitor cells to the blood circulation and an increase in the blood level of cytokines participating in hematopoiesis. The studies were carried out in patients with chronic cholelithiasis, undergoing elective open cholecystectomy under general anesthesia. An increase in the frequency of circulating CD34+ hematopoietic progenitor cells was seen between days 3 and 7 after surgery. Moreover, a significant increase in the percentage of immature cells of myeloid lineage (CD13+, CD14+, CD33+) was seen on the 1st and 3rd postoperative days. This could be the result of an expansion of the total bone marrow cell number after surgery and a subsequent release of these cells into the blood circulation. The changes in blood cell populations were accompanied by an increase in IL-6 on days 1, 3, and 7 following surgery, in IL-6sR on days 10 and 14 and in IL-8 on days 1 and 3. No significant changes in IL-1alpha, IL-1beta, IL-3 and IL-11 were noted. A small rise in GM-CSF was noted in few patients on the 3rd and 7th postoperative days. It is known that IL6 is involved in hematopoiesis, that the IL6-IL-6sR complex may induce both proliferation and differentiation of hematopoietic progenitor cells and that IL8 possesses progenitor cell mobilization properties. The appearance of hematopoietic progenitor cells in the blood following surgery may represent a process for the expansion of the immune cell pool after trauma and maintaining of the reserves at a certain level.

Adult↗

Lymphocyte interactions with extracellular matrix proteins and endothelium in renal allograft recipients.

Recent data indicate that extracellular matrix (ECM) proteins can provide costimulatory signals during the process of T cell activation. Those proteins accumulate in situ during allograft rejection; therefore, it may be expected that local ECM: T cell interactions may be relevant in the immunopathology of rejection. T cell adhesion from allograft of recipients with stable renal function (RAR-S) and patients with biopsy-proven chronic rejection (RAR-CH) to ECM proteins (collagen type IV, fibronectin, elastin) was measured. Furthermore, T cell: endothelial interactions in vitro were studied. Adhesion of PHA-activated T cells from both groups of allograft recipients to fibronectin, collagen type IV and elastin was significantly lower than in healthy blood donors. Moreover, similar pattern of activity was observed when T cell attachment to resting and activated endothelium was studied. There were no significant differences in the number of circulating CD45RO and CD4 positive T cells. We observed a higher (although not significantly) adhesion of the T cells to resting human dermal microvascular endothelial cells (HMEC) in the chronic stages of rejection, which can suggest that the immunosuppressive protocol used in the treatment of chronic rejection is insufficient to control immunopathologic phenomena occurring in that process. Therefore, it may be argued that too low immunosuppression can be one of the factors responsible for the development of this complication.

Cell Adhesion↗

Body distribution of syngeneic and allogeneic cells from vascularized bone marrow graft.

In the previous studies we showed that vascularized bone marrow graft (VBMtx) in transplanted rat hind limb brings about complete repopulation of syngeneic recipient BM cavities and lymphoid organs within 10 days. Transplantation of an equivalent number of bone marrow cells (BMC) in suspension did not produce repopulation until day 30. In this study we present data on transplantation of allogeneic VBM and compare them with those obtained in a syngeneic combination. In the LEW or BN to LEW combination BM cells were labelled with 51Cr, injected i.v., 24 h later the hind limb was amputated and transplanted to a LEW rat. BM cells emigrated from the transplanted limb to the recipient and distributed in BM cavities and lymphoid tissues. In the LEW to LEW combination the level of radioactivity in recipient tibia was after 24 h 0.85, in spleen 2.43, in mesenteric lymph node 0.52%/g of tissue, whereas in the BN to LEW model it was 0.11, 1.83 and 0.15%, respectively. The calculated numbers of BM cells which populated recipient tissues were 8-10-times lower in the allogeneic compared with syngeneic combination. This was probably due to the nonspecific elimination of some subsets of BM cells (allogeneic BMC cytotoxicity). Administration of anti-asialo GMI antiserum to the recipient abrogated the cytotoxic effect. Taken together, major differences in kinetics of seeding and repopulation of BMC from VBMTx were found. Elimination of recipient NK cells with AAGMI antiserum attenuated the nonspecific cytotoxic effect. This protocol allows protection of the grafted BMC and increases the efficacy of the transplant.

Animals↗

Microchimerism following allogeneic vascularized bone marrow transplantation--its possible role in induction of posttransplantation tolerance.

We have noticed that bone marrow transplanted in a vascularized limb graft providing a continuous supply of donor BMC may prolong the survival time of skin graft from the same donor. The question arises whether the raised microchimerism plays a role in the prolonged survival of skin allograft. The aim of the study was to follow the development of microchimerism after allogeneic vascularized bone marrow transplantation (VBMTx) concomitantly with the rejection processes of transplanted skin. The BN rats served as donors and LEW rats as recipients of VBMTx and free skin flap allograft. Hind limb was transplanted followed by a full-thickness skin graft on the dorsum. Cellular microchimerism was investigated in recipients of VBMTx and skin grafts in blood, spleen, mesenteric lymph node and bone marrow with monoclonal antibody OX27 directed against MHC class I polymorthic RTI on BN cells and quantitatively analysed in FACStar. In VBMTx group free skin flap survived 70 days after weaning of CsA. Intravenous infusion of BMC in suspension equivalent to that grafted in hind limb did not prolong skin graft survival after cessation of CsA therapy. Donor-derived cells could be detected in VBMTx recipients as long 70 days after wearing of CsA but not in recipients of i.v. suspension BMC grafting.

Animals↗

[The effect of hypolipidemia treatment on the function of kidney transplanted from cadavers].

The high prevalence of hypercholesterolemia (HCh) in kidney transplant recipients probably contributes to the high cardiovascular mortality of these patients. Additionally, HCh is a contributing factor to the progression of renal failure. We conducted a prospective, randomised study with low dose Lovastatin in 42 kidney transplant recipients during 32 weeks, focusing on side effect and kidney function 42 consecutive patients with kidney transplanted in our Institute, with stable renal function (creatinine level < 160 mmol/l) treated with ciclosporine, azathioprine, prednisone were enrolled for the study (regardless of the initial cholesterol level). Every second patient was given Lovastatin 20 mg/night. In the Lovastatin group total cholesterol (TC) and LDL concentration were significantly lower after 6 months of treatment (TC was reduced from 242.5 +/- 12.8 to 220 +/- 15.4 mg/dl, p < 0.05) in Lovastatin group whereas in control group it increased nonsignificantly. Similarly LDL in Lovastatin group decreased from 140.0 +/- 7.0 to 121.3 +/- 10.8 mg/dl, p < 0.02 whereas in control group it increased from 143.6 +/- 5.4 to 169.9 +/- 10.3 mg/dl, p < 0.01. HDL and trigliceride concentrations were unchanged. The Lovastatin treatment did not results in more adverse events than the placebo treatment. Notably, the tendency to increase creatinine level in Lovastatin group was observed from 1.59 +/- 0.17 to 1.74 +/- 0.22 in Lovastatin group versus 1.89 +/- 0.22 to 2.21 +/- 0.35 mg/dl (NS). Low dose Lovastatin treatment seems to be safe and efficient cholesterol-lowering procedure. However we did not observe beneficial effect on kidney graft function.

Adult↗

Comparative analysis of immunological reconstitution induced by vascularized bone marrow versus bone marrow cell transplantation.

We have reported previously that vascularized bone marrow transplantation (VBMT) in an orthotopic hind limb graft brings about complete repopulation of bone marrow cavities in lethally irradiated syngeneic recipients within 10 days. Intravenous infusion of an equivalent volume of bone marrow cell suspension was evidently less effective. The purpose of this study was to investigate the reconstitution of immunocompetent compartments of lethally irradiated syngeneic rats after VBMT. Lewis rat hind limbs were transplanted orthotopically into irradiated recipients. Ten days after irradiation and bone marrow transplantation, bone marrow, mesenteric lymph nodes, and sera from rats were harvested. Mesenteric lymph node lymphocytes were analyzed. The responsiveness for mesenteric lymph node lymphocytes (MLNL) to mitogens and cell proliferation in the presence of sera and bone marrow cell (BMC) culture supernatants were measured. Our studies have shown that vascularized bone marrow transplantation brings about rapid replenishment of lymphoid organs of lethally irradiated syngeneic recipients. The repopulating subsets are fully responsive to mitogens. Sera from reconstituting rats had no effect on the proliferation of mature lymphocytes. Intravenous infusion of a number of BMC in suspension equivalent to that grafted in hind limb transplant was less efficient in reconstitution of lymphoid tissue.

Animals↗

Blood cytokine levels rise even after minor surgical trauma.

The exact changes in cytokine production and clinical implications of the increased cytokine levels following operative trauma remain unclear. In this study, systemic production of a spectrum of cytokines, including IL1 alpha, IL1 beta, IL6, IL8, IL10, and IFN gamma, was examined in patients undergoing minor elective operative trauma. The levels of IL1 receptor antagonist (ra) and IL6 soluble receptor (sR) were also determined. Although there were no changes in IL1 alpha and IL1 beta plasma levels during the entire observation period, there was a significant rise in IL1 ra level in all patients between postoperative day 1 and postoperative day 14. A significant increase in the IL6 plasma level was seen on days 1, 3, and 7 after surgery and an increase in the IL6 sR level was observed on postoperative days 10 and 14. Interestingly, the IL8 plasma values had risen significantly on days 1 and 3 following the operation. In some patients, an elevation in IL10 plasma level was noted on days 1 and 3 postsurgery. Results demonstrated that even a minor surgical procedure such as cholecystectomy with uneventful wound healing was followed by an appearance in the blood circulation of significant levels of cytokines between day 1 and day 14 after surgery. These observations point to the necessity of searching for methods of down-regulating the systemic cytokine effects after surgical trauma for the routine postoperative management.

Adult↗

Predictor of transplanted kidney deterioration following pregnancy--daily urine protein loss or serum creatinine concentration?

Increasing number of female kidney recipients deciding to born a baby makes us to investigate the impact of pregnancy on graft survival. The aim of study was to find the parameter that would have the predictive value for graft function following delivery. Scr and P in 33 pregnant renal allograft recipients (mean age 27.1 +/- 6.1 yrs) treated with pred + aza + CsA were studied for 6 mo before, during and 6 mo following delivery. As measured only by Scr graft function was stable in all pts (1.4 +/- 0.05 mg/dl). Significant rise in Scr following pregnancy was found in 6 of 33 pts. This "unstable" group was compared with 27 patients with "stable" despite pregnancy graft function. Proteinuria, but not Scr differentiated groups prior to pregnancy. The estimation of P prior to conception seems to be more potent parameter to predict kidney graft deterioration following pregnancy than Scr alone. Increase in P during and following pregnancy in "unstable" pts may reflect the acceleration of subclinical (not yet manifested with rise of Scr) chronic graft rejection due to pregnancy-induced hiperfiltration.

Adolescent↗