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R Borota

Publications and source records attributed to R Borota.

At least 55 records · Page 3Linked to original sources
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[Clinical use of thrombopoietin (c-Mpl Ligand)].

INTRODUCTION: Results in clinical use of thrombopoietin have been published later than of other hematopoietic growth factors, because until recently the research was the least understood aspect of blood cell development. Reasons for this time gap were numerous, from inconvenient methods for measurement of thrombopoietin activity, to difficulties of its chemical purification. It is claimed recently that the understanding of platelet production has been profoundly advanced by the recombinant-gene synthesis and characterization of c-Mpl ligand (Megakaryocyte Growth and Development Factor), a substance which strongly enhances the proliferation of megakaryocytic line and the production of platelets. In this paper, some historical facts and biology of thrombopoietin are briefly discussed as well as the recent of the clinical use of thrombopoietin. THE HISTORY OF RESEARCH AND PRODUCTION OF THROMBOPOIETIN: The concept that the platelet production is underlying humoral regulation was first promoted by a group of Hungarian authors and they also named that humoral regulator--thrombopoietin. Further research followed in several countries including our own, and the initial studies proved that the serum of thrombocytopenic animals induced proliferation and maturation of megakaryocytic cell line and thrombocytosis in the peripheral blood of recipient animals. Later, when in vitro techniques were developed, it was shown that this humoral regulator has also a colony stimulating activity on megakaryocytic precursors. During the following two decades, studies of megakarycytopoiesis supported the hypothesis that two types of factors are involved in platelet production: early acting--megakaryocyte colony stimulating factors (Meg-CSF), and late acting--megakaryocyte potentiators, first of all thrombopoietin (TPO). However, extensive attempts on the purification of substances that either stimulate megakaryocyte development or augment platelet production failed to yield a homogeneous protein adequate for protein sequencing and cDNA cloning, the usual route which led to the production of other hematopoietic growth factors. Furthermore, a large number of other cytokines were described that possessed activity in various assays of megakaryocyte development. In spite of great number of accumulated data, it seemed in early 1990s that the production of a distinct, clinically useful lineage specific thrombopoietin will not be soon possible to achieve. The breakthrough occurred in 1994, when four groups of investigators published simultaneously their successful results on production of c-Mpl ligand, a substance which specifically binds to the Mpl receptors on megakaryocytes and has a very potent thrombocytopoietic effect. This production is based on genetic engineering and two companies (Kirin and Amgen) are already able to produce recombinant human thrombopoietin in large amounts, for clinical use. Although this substance is not commercially available yet, it passed the preclinical and clinical trials whose results are presented here. RESULTS OF THE PRECLINICAL TRIALS OF RECOMBINANT THROMBOPOIETIN: The chemical structure of human recombinant thrombopoietin (rTPO) is well defined, it is a glycoprotein consisting of 353 amino acids and molecular weight of 30 kD. The biologic actions of this molecule are in vitro: stimulation of megakaryocyte colony forming, endoreduplication of chromosomes and megakaryocyte maturation, and in vivo: increase of the number of progenitors and of megakaryocytes in the bone marrow, and an extensive elevation of platelet count in the peripheral blood 4-7 days after its application. Also, in synergism with other pluripotent cytokines, it can stimulate the proliferation of other progenitors including CD34+ stem cells. Based on these data it is considered that c-Mpl ligand is the main physiological humoral regulator of thrombocytopoiesis, having the biological actions both of MegCSF and TPO.

Animals↗
PubMedDate not supplied

[From a scientific idea to clinical use].

INTRODUCTION: In the nineteenth century, medicine, a former empiric skill, obtained its scientific basis owing to the development of physics, chemistry, biology, physiology, histology, biochemistry and other natural sciences. Fast progress in medicine was thus possible, but at the same time made the introduction of new scientific ideas into clinical use very difficult and therefore majority of them never reach satisfactory clinical application. Two examples from the author's own experience are presented here. FROM RADIOACTIVITY TO NUCLEAR MEDICINE: Soon after the discovery of radioactivity, George Hevesy gave a scientific basis for its use as a diagnostic and therapeutic tool in medicine. The first nuclear medicine laboratory was established in Vojvodina in 1963 and during the following twenty years, clinical application of radioactive tracers was developed very successfully in this area. But in the subsequent years the use of nuclear medicine methods declined dramatically for many reasons, mainly because of unsatisfactory cost/benefit ratio. FROM EXPERIMENTAL BLEEDING TO ERYTHROPOIETIN: The scientific idea of humoral regulation of hematopoiesis was proposed by Carnot at the beginning of the twentieth century, but it was introduced for clinical application only a hundred years later. It became possible by pharmaceutical production of recombinant hematopoietic growth factors by genetic engineering, and some of them, erythropoietin and granulocyte CSF, are available at high prices. They were used successfully for anemia in renal failure and some cases of neutropenic syndrome respectively, but compared to the initial expectations and quantity of research invested this is an unsatisfactory result. INSTEAD OF CONCLUSION: The introduction of these two presented scientific ideas into clinical application failed because of inadequate organization of medical scientific research and lack of financial support.

Diffusion of Innovation↗
PubMedDate not supplied

[Use of radionuclide quantitative analysis in routine diagnosis of metabolic bone diseases].

Global and regional quantity indexes of metabolic bone activities are determined on the basis of given scintigraphic dose for skeleton examination. The calculation of all analyzed indexes was carried out in all cases of the control group and patients with established disturbance of bone tissue metabolism. When choosing the method used in the routine work, apart from diagnostic value of analysis numerous criteria have been respected. The analyzed global quantity indexes of metabolic bone activity adapted to conditions of routine work have similar diagnostic value, while the best regional index relating bone soft tissue is the one concerned with the upper leg. As the examined quantity indexes enable more reliable interpretation of the scintigraphic findings, in everyday work the scintigraphic examination should be filled in by determination of corrected retention of activity in the whole body and calculation of radiosotope analysis significantly depend one the kidney function and urine elimination.

Bone Diseases, Metabolic↗
PubMedDate not supplied

[The work of the Serbian Medical Society--the Medical Society of Vojvodina under present conditions].

The content of work of medical society in Vojvodina has always been primarily set by the founder with its main goal: the physicians professional and scientific specialization. In recent years there have been many socio-political, moral and social changes which have had great influence on the work of medical organizations. The poverty of the whole society, especially of the health service, has completely disabled organization of big professional meeting so that the professional activity meant mostly one-day meetings in health institutions. Although there was a threatening possibility to stop publishing the professional journal "Medical Review" after 47 years of appearing in print, today problem is solved by financial help by the government. Apart from professional work, other activities of physicians organizations are becoming important today. An appropriate attitude toward war generally speaking was declared in 1992 as an "Appeal for Peace". A request was made to distinguish profession and politics in the work of physicians so that the society acted only as a professional organization without political involvement and there is an initiative to found a medical association. Physicians gave their best in this hard situation to maintain work of the health service, but as it was not possible any more at one moment, an extra congress of physicians of Serbia was organized verifying serious consequences of war considering the health of the whole population. Society has been extremely engaged in solving numerous problems of ethics which have appeared due to war such as lack of medicines and health care materials as well as abuse of the private medical practice.

Periodicals as Topic↗