[Stem cell transplantation: new method of treatment].
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Biomedical subjects
Publications and source records attributed to Leszek Paczek.
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UNLABELLED: Hepatocellular carcinoma is one of the most common malignancies worldwide. Invasiveness of this tumour seems to be related to degradation of extracellular matrix. Such proteolytic enzymes as: cathepsin B and L, plasmin, collagenase and trypsin are thought to play a pivotal role in this process. Enzymatic activity depends on balance between enzymes and their inhibitors and--moreover--on interactions among these enzymes. The purpose of our study was to evaluate enzymatic activity of cathepsin B, cathepsin B and L, plasmin, collagenase and trypsin in patients with hepatocellular carcinoma in liver tissue and in peripheral blood. Then correlations between activity of enzymes (mentioned above) and clinical status, pathological findings and laboratory tests were assessed. Our study was conducted on 14 patients who underwent surgery because of hepatocellular carcinoma. Tissue samples were obtained during surgery from neoplastic area and from non-neoplastic area. Peripheral blood was withdrawn before surgery and within early post-operative period. Proteolytic activity of these enzymes was determined with use of fluorometric assay. Enzymatic activity in tissue samples was referred to protein concentration (BCA assay) and to DNA concentration (fluorometric assay). RESULTS: Proteolytic activity of plasmin and trypsin in neoplastic tissue were significantly lower as compared to non-neoplastic area of these patients (p = 0.0356; p = 0.0412, respectively). Activity of the remaining enzymes: cathepsin B, cathepsin B and L and collagenase did not differ significantly. No difference was demonstrated between activity of enzymes in peripheral blood withdrawn before surgery and in postoperative period. There was a statistically significant inverse correlation between serum AFP level and enzymatic activity of cathepsin B, cathepsin B and L and collagenase in tumor tissue. Lower activity of all investigated enzymes was observed in tumor tissue of HBV related hepatocellular carcinoma in comparison with the remaining tissue samples. Correlation between patients age and activity of enzymes was not statistically significant. CONCLUSION: Although the evaluation of presented enzymatic profile did not allow for the assessment of associations between investigated enzymes, our results demonstrated correlations between proteolytic activity of enzymes and serum AFP level, viral status, but it requires further investigations.
Type 2 diabetes mellitus is a social and civilization-related disease that leads to various micro- and macroangiopathic complications, including diabetic nephropathy. At present, the most sensitive and non-invasive indicator of the progression of diabetic nephropathy is microalbuminuria. Morphological features such as accumulation of extracellular matrix proteins, thickening of glomerules' basement membranes are prior to microalbuminuria. The aim of our clinical study was to establish whether urine and serum TGF beta 1 levels may be significant in prognosing and evaluating a risk for developing diabetic nephropathy. The trial was carried out in 68 patients with type 2 diabetes mellitus and a group of 10 healthy subjects served as control. Urine and serum TGF beta 1 concentrations were evaluated, as well as basic laboratory parameters. After one-year-observation serum creatinine level and microalbuminuria value were investigated in 60 patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus both urine and serum TGF beta 1 concentration were elevated. After one-year-observation of patients with type 2 diabetes mellitus it was established that the increase of serum creatinine concentration and that of microalbuminuria value were higher in those patients, whose initial TGF beta 1 levels exceeded normal values. A positive correlation between urine TGF beta 1 level and the progression of renal failure measured by the increase of serum creatinine level was observed. In conclusion, our findings indicate that urine TGF beta 1 level may be a good prognostic factor of the development of diabetic nephropathy in the course of diabetes mellitus.
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Diabetes mellitus (DM) is the most common metabolic disease, an independent risk factor of coronary disease, and shortens lifetime in all populations of patients, including kidney transplant recipients. Patients after kidney transplantation are exceptionally predisposed to develop or to exacerbate the preexisting DM. Age, DM in family, CMV infections, genetic factor (HLA A26 and B27), immunosuppressive treatment with steroids or calcineurin inhibitors belong to the major risk factors of diabetes. We analyzed 1300 renal transplant recipients in our center. Out of them 153 suffered from DM. DM de novo revealed 80 pts. Mean age in type I pts was 44.88 years and in type II pts was 57.27 years. De novo diabetics were 56.41 years old in average. CMV infection, potentially pathogenic in development of DM de novo, coexisted in 7.5% of these cases as frequently as in whole TPN population. Most frequently detected HLA antigens were: A2, B8 and DR5. Use of cyclosporine and tacrolimus promoted incidence of DM. We conclude, that low percentage of de novo DM in patients after renal transplantation may result from flexibility in administration of immunosuppressive regimens. Cyclosporine and tacrolimus treatment was switched to sirolimus or mycophenolate mofetil when the glucose intolerance was detected to prevent development of DM.
Progression to end-stage renal failure is the final common pathway of many forms of glomerular diseases, independent of the type of initial insult. Tubulointerstitial fibrosis is tis near invariable finding and significant prognostic feature. We have reviewed immunological (cytokines, inflammatory cells) and nonimmunological factors (extracellular matrix proteins and proteolytic enzymes), being involved in mechanisms leading from glomerular disease to tubulointerstitial scarring, from the point of view of potential clinical usefulness of measuring its urine activities and levels to noninvasive diagnostic of kidney diseases.
Diabetic nephropathy is major long-term complication of diabetes mellitus a social and civilization-related disease. At present, the most sensitive and non-invasive indicator of the progression of diabetic nephropathy is microalbuminuria. Morphological features such as accumulation of extracellular matrix proteins, thickening of glomerules' basement membranes are prior to microalbuminuria. The aim of our clinical study was to establish whether urine and serum TGF-beta 1 and IL-6 levels may be significant in prognosing and evaluating a risk for developing diabetic nephropathy. The trial was carried out in 68 patients with type II diabetes mellitus and a group of 10 healthy subjects served as control. Urine and serum TGF-beta 1 concentrations were evaluated, as well as, basic laboratory parameters. After one-year-observation serum creatinine level and microalbuminuria value were investigated in 60 patients with type II diabetes mellitus. In patients with type II diabetes mellitus both urine and serum TGF-beta 1 and IL-6 were elevated. After one-year-observation of patients with type II diabetes mellitus it was established that the increase of serum creatinine concentrations values were higher in those patients, whose initial TGF-beta 1 levels exceeded normal values. A positive correlation between urine TGF-beta 1 level and the progression of renal failure measured by the increase of serum creatinine level was observed. In conclusion, our findings indicate that urine TGF-beta 1 and IL-6 levels may be a good prognostic factor of the development of diabetic nephropathy in the course of diabetes mellitus.
The vascular hallmark of chronic rejection (CR), as well as of atherosclerosis, is initial hyperplasia. It results from migration and proliferation of vascular smooth muscle cell and increased deposition of extracellular matrix proteins. A possible mechanism responsible for formation of neointima is the release of growth factors and cytokines, such as: transforming growth factor beta (TGF-beta), tumour necrosis factor alfa (TNF-alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6). The expression of these factors in the renal artery wall of chronically rejected allografts was quantified. The renal artery samples were obtained from patients with chronic renal allograft rejection, undergoing graftectomy (n = 11) and patients with autosomal dominant polycystic kidney disease (ADPKD), undergoing nephrectomy (n = 4). Total RNA was isolated and the expression of mRNA for TGF-beta, TNF-alpha, IL-1 and IL-6 was measured using a real time PCR. In patients with CR the expression levels of TGF-beta, TNF-alpha and IL-1 mRNA were higher than in control group. No difference between groups was detected for IL-6. In both groups a correlation was detected between age and TGF-beta expression. The increased expression of TGF-beta, TNF-alpha and IL-1 may be a key factor in the neointimal formation and pathogenesis of CR. The increase in the TGF-b expression with age might be a protective mechanism in atherosclerosis.
Prevalence of arterial hypertension suddenly rose in patients after renal transplantation since cyclosporine A was introduced. Arterial hypertension is now diagnosed in 67-90% of patients after renal transplantation. It has not only negative effect on cardiovascular system but also shortens survival of renal graft. Ambulatory blood pressure monitoring (ABPM) enables evaluation of diumal profile of BP and efficacy of treatment. This diagnostic tool is very useful in the management of these patients. Nocturnal hypertension was 2.5 times more frequent than daytime elevation of BP in the group of 58 consecutive renal transplant patients treated with calcineurin inhibitors who were assessed by ABPM at our department. Lack of nocturnal dip of BP was observed in most of the patients. Conversion from calcineurin inhibitors (cyclosporine A, tacrolimus) to sirolimus or mycophenolate mofetil may improve BP profile in this group of patients.
Chronic antiinflammatory treatment is required in autoimmunologic dermatoses. Tacrolimus ointment (Protopic) an inhibitor of calcineurin, is the first topical nonsteroidal immunosuppressant for the last 50 years. Pimecrolimus (ASM 981), a newer calcineurin inhibitor developed for atopic dermatitis treatment has the same mode of action and altered skin penetration profile as takrolimus. Their structure, mechanism of immunosuppressive action, efficacy and safety in atopic dermatitis and other inflammatory dermatitides was described in this article. The attention was paid to systemic and in topical treatment, their intact and injured skin penetration profile, optimal doses, costs and perspectives of broad use of these drugs in dermatology were described.