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1. MODERATION OF QUANTITATIVE CHANGES OF REGENERATING ERYTHROPOIETIC CELLS BY EXTRACELLULAR UBIQUITIN

Author

R, Sujashvili, I, Ioramashvili, K, Mazmishvili, S, Tsitsilashvili, and M, Gamkrelidze

Subjects
Mice, Radiation Injuries, Experimental, Cesium Radioisotopes, Ubiquitin, Cell Cycle, Animals, Regeneration, Bone Marrow Cells, Hematopoiesis
Abstract

Hematological disorders caused by radiation remain the most challenging problem of the last decades. Environmental radiation, as well as medical application of radiation causes serious problems especially from the point of view of blood formation and passage of blood functional cells. Bone marrow emptying followed by the rise of immature cells in the bloodstream is the main pathology that must be eliminated. The importance of the issue is well recognized by all investigators. Opening of agents for regulation of spontaneous regeneration of hematopoietic cell lines is of prime importance in cancer treatment. Ubiquitin is a globular protein of eukaryotic cells. It is involved in regulation of cell cycle. Recently we studied the influence of extracellular ubiquitin on regeneration of leukopoiesis. Interestingly what is its effect on erythropoietic cell lines? Erythrocytes are more resistant to irradiation, than nucleic cells. Their depletion-elevation picks during blood regeneration clearly reveal low sharpness. Nevertheless, depletion of erythropoietic cells if not treated, may cause short- and long-term side effects. We studied the influence of intraperitoneally injected ubiquitin on the process of spontaneous regeneration of erythropoietic cell lines of bone marrow (BM) and peripheral blood (PB) after irradiation in mice. The source of radiation was 137Cs with dose rate 1Gy/min., the duration of exposure 3 min and 5 min. Nonlinear white mice of 22±2 gr. were used for experiment. Animals were divided into five groups (6 animals in each group): the first control group of intact mice; the second test group of mice irradiated by the sublethal dose of 3Gy; the third test group of mice irradiated by 3Gy intraperitoneally injected by ubiquitin by the dose of 100µg/ml at the 72 hour point after irradiation; the fourth test group of mice irradiated by the dose of LD50 5Gy; the fifth test group of mice irradiated by 5Gy intraperitoneally injected by ubiquitin at the 72 hour point after irradiation. PB and BM samples from the control group and the test groups of mice have been taken every 24 hours after irradiation during 7 days. Microscopy and statistical methods have been implicated for calculation of cell count of PB and BM. Analyzing the results we concluded that Ubiquitin prevents depletion-elevation picks of erythrocytes and erythroblasts regardless of the severity of damage caused by different doses of radiation indicating normalization of the regeneration process after irradiation. The study is important for opening new therapeutic agents for normalization of regeneration hematopoiesis after irradiation.

Published
2019

2. Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)(Clin Transl Allergy (2016) 6 (29) DOI: 10.1186/s13601-016-0116-9)

Author

Bousquet, J. Farrell, J. Crooks, G. Hellings, P. Bel, E.H. Bewick, M. Chavannes, N.H. De Sousa, J.C. Cruz, A.A. Haahtela, T. Joos, G. Khaltaev, N. Malva, J. Muraro, A. Nogues, M. Palkonen, S. Pedersen, S. Robalo-Cordeiro, C. Samolinski, B. Strandberg, T. Valiulis, A. Yorgancioglu, A. Zuberbier, T. Bedbrook, A. Aberer, W. Adachi, M. Agusti, A. Akdis, C.A. Akdis, M. Ankri, J. Alonso, A. Annesi-Maesano, I. Ansotegui, I.J. Anto, J.M. Arnavielhe, S. Arshad, H. Bai, C. Baiardini, I. Bachert, C. Baigenzhin, A.K. Barbara, C. Bateman, E.D. Beghé, B. Kheder, A.B. Bennoor, K.S. Benson, M. Bergmann, K.C. Bieber, T. Bindslev-Jensen, C. Bjermer, L. Blain, H. Blasi, F. Boner, A.L. Bonini, M. Bonini, S. Bosnic-Anticevitch, S. Boulet, L.P. Bourret, R. Bousquet, P.J. Braido, F. Briggs, A.H. Brightling, C.E. Brozek, J. Buhl, R. Burney, P.G. Bush, A. Caballero-Fonseca, F. Caimmi, D. Calderon, M.A. Calverley, P.M. Camargos, P.A.M. Canonica, G.W. Camuzat, T. Carlsen, K.H. Carr, W. Carriazo, A. Casale, T. Cepeda Sarabia, A.M. Chatzi, L. Chen, Y.Z. Chiron, R. Chkhartishvili, E. Chuchalin, A.G. Chung, K.F. Ciprandi, G. Cirule, I. Cox, L. Costa, D.J. Custovic, A. Dahl, R. Dahlen, S.E. Darsow, U. De Carlo, G. De Blay, F. Dedeu, T. Deleanu, D. De Manuel Keenoy, E. Demoly, P. Denburg, J.A. Devillier, P. Didier, A. Dinh-Xuan, A.T. Djukanovic, R. Dokic, D. Douagui, H. Dray, G. Dubakiene, R. Durham, S.R. Dykewicz, M.S. El-Gamal, Y. Emuzyte, R. Fabbri, L.M. Fletcher, M. Fiocchi, A. Fink Wagner, A. Fonseca, J. Fokkens, W.J. Forastiere, F. Frith, P. Gaga, M. Gamkrelidze, A. Garces, J. Garcia-Aymerich, J. Gemicioǧlu, B. Gereda, J.E. González Diaz, S. Gotua, M. Grisle, I. Grouse, L. Gutter, Z. Guzmán, M.A. Heaney, L.G. Hellquist-Dahl, B. Henderson, D. Hendry, A. Heinrich, J. Heve, D. Horak, F. Hourihane, J.O.B. Howarth, P. Humbert, M. Hyland, M.E. Illario, M. Ivancevich, J.C. Jardim, J.R. Jares, E.J. Jeandel, C. Jenkins, C. Johnston, S.L. Jonquet, O. Julge, K. Jung, K.S. Just, J. Kaidashev, I.P. Khaitov, M.R. Kalayci, O. Kalyoncu, A.F. Keil, T. Keith, P.K. Klimek, L. Koffi N'Goran, B. Kolek, V. Koppelman, G.H. Kowalski, M.L. Kull, I. Kuna, P. Kvedariene, V. Lambrecht, B. Lau, S. Larenas-Linnemann, D. Laune, D. Le, L.T.T. Lieberman, P. Lipworth, B. Li, J. Lodrup Carlsen, K. Louis, R. MacNee, W. Magard, Y. Magnan, A. Mahboub, B. Mair, A. Majer, I. Makela, M.J. Manning, P. Mara, S. Marshall, G.D. Masjedi, M.R. Matignon, P. Maurer, M. Mavale-Manuel, S. Melén, E. Melo-Gomes, E. Meltzer, E.O. Menzies-Gow, A. Merk, H. Michel, J.P. Miculinic, N. Mihaltan, F. Milenkovic, B. Mohammad, G.M.Y. Molimard, M. Momas, I. Montilla-Santana, A. Morais-Almeida, M. Morgan, M. Mösges, R. Mullol, J. Nafti, S. Namazova-Baranova, L. Naclerio, R. Neou, A. Neffen, H. Nekam, K. Niggemann, B. Ninot, G. Nyembue, T.D. O'Hehir, R.E. Ohta, K. Okamoto, Y. Okubo, K. Ouedraogo, S. Paggiaro, P. Pali-Schöll, I. Panzner, P. Papadopoulos, N. Papi, A. Park, H.S. Passalacqua, G. Pavord, I. Pawankar, R. Pengelly, R. Pfaar, O. Picard, R. Pigearias, B. Pin, I. Plavec, D. Poethig, D. Pohl, W. Popov, T.A. Portejoie, F. Potter, P. Postma, D. Price, D. Rabe, K.F. Raciborski, F. Radier Pontal, F. Repka-Ramirez, S. Reitamo, S. Rennard, S. Rodenas, F. Roberts, J. Roca, J. Rodriguez Mañas, L. Rolland, C. Roman Rodriguez, M. Romano, A. Rosado-Pinto, J. Rosario, N. Rosenwasser, L. Rottem, M. Ryan, D. Sanchez-Borges, M. Scadding, G.K. Schunemann, H.J. Serrano, E. Schmid-Grendelmeier, P. Schulz, H. Sheikh, A. Shields, M. Siafakas, N. Sibille, Y. Similowski, T. Simons, F.E.R. Sisul, J.C. Skrindo, I. Smit, H.A. Solé, D. Sooronbaev, T. Spranger, O. Stelmach, R. Sterk, P.J. Sunyer, J. Thijs, C. To, T. Todo-Bom, A. Triggiani, M. Valenta, R. Valero, A.L. Valia, E. Valovirta, E. Van Ganse, E. Van Hage, M. Vandenplas, O. Vasankari, T. Vellas, B. Vestbo, J. Vezzani, G. Vichyanond, P. Viegi, G. Vogelmeier, C. Vontetsianos, T. Wagenmann, M. Wallaert, B. Walker, S. Wang, D.Y. Wahn, U. Wickman, M. Williams, D.M. Williams, S. Wright, J. Yawn, B.P. Yiallouros, P.K. Yusuf, O.M. Zaidi, A. Zar, H.J. Zernotti, M.E. Zhang, L. Zhong, N. Zidarn, M. Mercier, J.

Published
2017

3. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

Author

Bousquet, J. Hellings, P.W. Agache, I. Bedbrook, A. Bachert, C. Bergmann, K.C. Bewick, M. Bindslev-Jensen, C. Bosnic-Anticevitch, S. Bucca, C. Caimmi, D.P. Camargos, P.A.M. Canonica, G.W. Casale, T. Chavannes, N.H. Cruz, A.A. De Carlo, G. Dahl, R. Demoly, P. Devillier, P. Fonseca, J. Fokkens, W.J. Guldemond, N.A. Haahtela, T. Illario, M. Just, J. Keil, T. Klimek, L. Kuna, P. Larenas-Linnemann, D. Morais-Almeida, M. Mullol, J. Murray, R. Naclerio, R. O'Hehir, R.E. Papadopoulos, N.G. Pawankar, R. Potter, P. Ryan, D. Samolinski, B. Schunemann, H.J. Sheikh, A. Simons, F.E.R. Stellato, C. Todo-Bom, A. Tomazic, P.V. Valiulis, A. Valovirta, E. Ventura, M.T. Wickman, M. Young, I. Yorgancioglu, A. Zuberbier, T. Aberer, W. Akdis, C.A. Akdis, M. Annesi-Maesano, I. Ankri, J. Ansotegui, I.J. Anto, J.M. Arnavielhe, S. Asarnoj, A. Arshad, H. Avolio, F. Baiardini, I. Barbara, C. Barbagallo, M. Bateman, E.D. Beghé, B. Bel, E.H. Bennoor, K.S. Benson, M. Białoszewski, A.Z. Bieber, T. Bjermer, L. Blain, H. Blasi, F. Boner, A.L. Bonini, M. Bonini, S. Bosse, I. Bouchard, J. Boulet, L.P. Bourret, R. Bousquet, P.J. Braido, F. Briggs, A.H. Brightling, C.E. Brozek, J. Buhl, R. Bunu, C. Burte, E. Bush, A. Caballero-Fonseca, F. Calderon, M.A. Camuzat, T. Cardona, V. Carreiro-Martins, P. Carriazo, A.M. Carlsen, K.H. Carr, W. Cepeda Sarabia, A.M. Cesari, M. Chatzi, L. Chiron, R. Chivato, T. Chkhartishvili, E. Chuchalin, A.G. Chung, K.F. Ciprandi, G. De Sousa, J.C. Cox, L. Crooks, G. Custovic, A. Dahlen, S.E. Darsow, U. Dedeu, T. Deleanu, D. Denburg, J.A. De Vries, G. Didier, A. Dinh-Xuan, A.T. Dokic, D. Douagui, H. Dray, G. Dubakiene, R. Durham, S.R. Du Toit, G. Dykewicz, M.S. Eklund, P. El-Gamal, Y. Ellers, E. Emuzyte, R. Farrell, J. Fink Wagner, A. Fiocchi, A. Fletcher, M. Forastiere, F. Gaga, M. Gamkrelidze, A. Gemicioǧlu, B. Gereda, J.E. Van Wick, R.G. González Diaz, S. Grisle, I. Grouse, L. Gutter, Z. Guzmán, M.A. Hellquist-Dahl, B. Heinrich, J. Horak, F. Hourihane, J.O.B. Humbert, M. Hyland, M. Iaccarino, G. Jares, E.J. Jeandel, C. Johnston, S.L. Joos, G. Jonquet, O. Jung, K.S. Jutel, M. Kaidashev, I.P. Khaitov, M. Kalayci, O. Kalyoncu, A.F. Kardas, P. Keith, P.K. Kerkhof, M. Kerstjens, H.A.M. Khaltaev, N. Kogevinas, M. Kolek, V. Koppelman, G.H. Kowalski, M.L. Kuitunen, M. Kull, I. Kvedariene, V. Lambrecht, B. Lau, S. Laune, D. Le, L.T.T. Lieberman, P. Lipworth, B. Li, J. Lodrup Carlsen, K.C. Louis, R. Lupinek, C. MacNee, W. Magar, Y. Magnan, A. Mahboub, B. Maier, D. Majer, I. Malva, J. Manning, P. De Manuel Keenoy, E. Marshall, G.D. Masjedi, M.R. Mathieu-Dupas, E. Maurer, M. Mavale-Manuel, S. Melén, E. Melo-Gomes, E. Meltzer, E.O. Mercier, J. Merk, H. Miculinic, N. Mihaltan, F. Milenkovic, B. Millot-Keurinck, J. Mohammad, Y. Momas, I. Mösges, R. Muraro, A. Namazova-Baranova, L. Nadif, R. Neffen, H. Nekam, K. Nieto, A. Niggemann, B. Nogueira-Silva, L. Nogues, M. Nyembue, T.D. Ohta, K. Okamoto, Y. Okubo, K. Olive-Elias, M. Ouedraogo, S. Paggiaro, P. Pali-Schöll, I. Palkonen, S. Panzner, P. Papi, A. Park, H.S. Passalacqua, G. Pedersen, S. Pereira, A.M. Pfaar, O. Picard, R. Pigearias, B. Pin, I. Plavec, D. Pohl, W. Popov, T.A. Portejoie, F. Postma, D. Poulsen, L.K. Price, D. Rabe, K.F. Raciborski, F. Roberts, G. Robalo-Cordeiro, C. Rodenas, F. Rodriguez-Mañas, L. Rolland, C. Roman Rodriguez, M. Romano, A. Rosado-Pinto, J. Rosario, N. Rottem, M. Sanchez-Borges, M. Sastre-Dominguez, J. Scadding, G.K. Scichilone, N. Schmid-Grendelmeier, P. Serrano, E. Shields, M. Siroux, V. Sisul, J.C. Skrindo, I. Smit, H.A. Solé, D. Sooronbaev, T. Spranger, O. Stelmach, R. Sterk, P.J. Strandberg, T. Sunyer, J. Thijs, C. Triggiani, M. Valenta, R. Valero, A. Van Eerd, M. Van Ganse, E. Van Hague, M. Vandenplas, O. Varona, L.L. Vellas, B. Vezzani, G. Vazankari, T. Viegi, G. Vontetsianos, T. Wagenmann, M. Walker, S. Wang, D.Y. Wahn, U. Werfel, T. Whalley, B. Williams, D.M. Williams, S. Wilson, N. Wright, J. Yawn, B.P. Yiallouros, P.K. Yusuf, O.M. Zaidi, A. Zar, H.J. Zernotti, M.E. Zhang, L. Zhong, N. Zidarn, M.

Abstract

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease. © 2016 The Author(s).

Published
2016

4. The regulation of defect concentrations by means of separation layer in wide-band II-VI compounds

Author

T G Khulordava, E E Kekelidze, M M Sharvashidze, N M Gamkrelidze, T V Butkhuzi, Kh V Gelovani, and N. Kekelidze

Subjects
Photoluminescence, Materials science, Chemical substance, Photoconductivity, Inorganic chemistry, Analytical chemistry, Conductivity, Condensed Matter Physics, Electronic, Optical and Magnetic Materials, Transition metal, Materials Chemistry, Electrical and Electronic Engineering, Science, technology and society, Ohmic contact, Stoichiometry
Abstract

The inversion of conductivity in II-VI binary compounds is possible by separating layers (gold and semiconducting layers). P-type (ZnS) and high ohmic n-type (ZnO) samples are obtained by using a gold separating layer. By using a semiconducting ZnO layer as the separating layer it is possible to regulate the relative concentration of components in the base crystal of newly grown layers. This made it possible to obtain stoichiometric n-type and also p-type ZnO and ZnS monocrystal layers.

Published
2001
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5. Plastid DNA sequence diversity in a worldwide set of grapevine cultivars (Vitis vinifera L. subsp. vinifera)

Author

Mari Gogniashvili, V. Tabidze, S. C. Hsu, Barbara A. Schaal, James B. Beck, M. Glonti, P. This, Tengiz Beridze, M. Gamkrelidze, I. Pipia, V. Gotsiridze, R. Bacilieri, Agricultural University of Georgia, Ilia State University [Tbilisi], Washington University in Saint Louis (WUSTL), Diversité et adaptation des plantes cultivées (UMR DIAPC), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Research Institute of Horticulture, Viticulture and Oenology, Durmishidze Institute of Biochemistry and Biotechnology, University of Washington, Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
0106 biological sciences, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, grape DNA, Horticulture, Biology, 01 natural sciences, DNA sequencing, rp116 intron, diversity, domestication, 03 medical and health sciences, vitis vinifera, Genetic variation, Botany, PCR amplification, séquençage, Food and Nutrition, Cultivar, Plastid, Domestication, caucase, 030304 developmental biology, grapes, diversité, 0303 health sciences, Genetic diversity, mer Noire, Haplotype, fungi, food and beverages, sequencing, fruit, viticulture, géorgie, Agricultural sciences, grapevine, raisin, Alimentation et Nutrition, trnH-psbA intergenic spacer, Key (lock), europe, vigne, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Sciences agricoles, 010606 plant biology & botany
Abstract

UMR AGAP Equipe Diversité, adaptation et amélioration de la vigne (DAAV); DNA sequence diversity was investigated at two plastid regions (the trnH-psbA intergenic spacer and the rpl16 intron) in a geographically diverse group of 113 cultivated grape samples. This group included 40 samples from the Republic of Georgia, home to over 500 grape cultivars and the earliest archaeological evidence of grape domestication. The greater Caucasus region in which Georgia lies is widely believed to be the area in which grape domestication began, and the study of genetic diversity in this region is viewed as key to understanding grape domestication in general. Four plastid haplotypes are evident in the 113 samples, and are designated by their character-states at each of the 3 polymorphic positions: (AAA)–23 samples, (ATT)–29 samples, (GTA)–34 samples, and (ATA)–27 samples. The AAA haplotype was only observed in Georgian samples, and these 23 “Rkatsiteli” group cultivars originate mostly from eastern Georgia. Contrast this group with the nine Georgian cultivars (23%) of the “Chkhaveri-Pinot noir” group (GTA), most of which are cultivated in western Georgia near the Black Sea coast. The observation that the Georgian cultivars exhibited both unique plastid DNA variation (the AAA haplotype) and all other observed plastid haplotypes is consistent with previous studies that have observed both unique and high levels of genetic variation in wild grape (V. vinifera subsp. sylvestris) in the greater Caucasus region.

Published
2010
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6. [Mechanisms of gamma-inducible death of Jurkat cells line]

Author

M M, Gamkrelidze, N D, Bezhitashvili, A T, Pavliashvili, T V, Mchedlishvili, and T V, Sanikidze

Subjects
Jurkat Cells, Gamma Rays, Humans, Apoptosis, Dose-Response Relationship, Radiation, Radiation Injuries
Abstract

Mechanisms of radio-inducible death of Jurkat cells were investigated. Human lymphoblastoid T-cell line Jurkat is widely established model for studying apoptosis mechanisms. The cell was radiated by "Teragam" (Czech Republic) by dose 2 g during 1 minute. After radiation cells were incubated at standard conditions during 24 hours. After gamma radiation in cell population amount of cells in gaplois (apoptotic G 0) stage was increased 8,2 folds, in diplois (G 0/G1) stage - by 17%, in synthetic (S) stage decreased by 35% and tetraploid (G2/M) stage by 73% in comparison to control group. It was revealed intensive production of free radicals of oxygen and nitric oxide and decreasing activity of antioxidant enzymes (superoxidismutasa, catalasa and glutathione peroxidase). Revealed dependence between intensification of apoptosis and radiation-induced arrest of cell cycle G2/M phase may be determined by excess amount of free oxygen and nitrogen radicals generated in Jurkat cells as a result of nondirect effects of low doses of gamma radiation.

Published
2008

7. MODERATION OF QUANTITATIVE CHANGES OF REGENERATING ERYTHROPOIETIC CELLS BY EXTRACELLULAR UBIQUITIN.

Author

Sujashvili R, Ioramashvili I, Mazmishvili K, Tsitsilashvili S, and Gamkrelidze M

Subjects
Animals, Cell Cycle radiation effects, Mice, Ubiquitin administration & dosage, Bone Marrow Cells drug effects, Cesium Radioisotopes, Hematopoiesis drug effects, Radiation Injuries, Experimental, Regeneration drug effects, Ubiquitin pharmacology
Abstract

Hematological disorders caused by radiation remain the most challenging problem of the last decades. Environmental radiation, as well as medical application of radiation causes serious problems especially from the point of view of blood formation and passage of blood functional cells. Bone marrow emptying followed by the rise of immature cells in the bloodstream is the main pathology that must be eliminated. The importance of the issue is well recognized by all investigators. Opening of agents for regulation of spontaneous regeneration of hematopoietic cell lines is of prime importance in cancer treatment. Ubiquitin is a globular protein of eukaryotic cells. It is involved in regulation of cell cycle. Recently we studied the influence of extracellular ubiquitin on regeneration of leukopoiesis. Interestingly what is its effect on erythropoietic cell lines? Erythrocytes are more resistant to irradiation, than nucleic cells. Their depletion-elevation picks during blood regeneration clearly reveal low sharpness. Nevertheless, depletion of erythropoietic cells if not treated, may cause short- and long-term side effects. We studied the influence of intraperitoneally injected ubiquitin on the process of spontaneous regeneration of erythropoietic cell lines of bone marrow (BM) and peripheral blood (PB) after irradiation in mice. The source of radiation was 137Cs with dose rate 1Gy/min., the duration of exposure 3 min and 5 min. Nonlinear white mice of 22±2 gr. were used for experiment. Animals were divided into five groups (6 animals in each group): the first control group of intact mice; the second test group of mice irradiated by the sublethal dose of 3Gy; the third test group of mice irradiated by 3Gy intraperitoneally injected by ubiquitin by the dose of 100µg/ml at the 72 hour point after irradiation; the fourth test group of mice irradiated by the dose of LD50 5Gy; the fifth test group of mice irradiated by 5Gy intraperitoneally injected by ubiquitin at the 72 hour point after irradiation. PB and BM samples from the control group and the test groups of mice have been taken every 24 hours after irradiation during 7 days. Microscopy and statistical methods have been implicated for calculation of cell count of PB and BM. Analyzing the results we concluded that Ubiquitin prevents depletion-elevation picks of erythrocytes and erythroblasts regardless of the severity of damage caused by different doses of radiation indicating normalization of the regeneration process after irradiation. The study is important for opening new therapeutic agents for normalization of regeneration hematopoiesis after irradiation.

Published
2019

8. ALTERED MICROCIRCULATION IN SEPTIC SHOCK.

Author

Ratiani L, Gamkrelidze M, Khuchua E, Khutsishvili T, Intskirveli N, and Vardosanidze K

Subjects
Hemodynamics, Humans, Nitric Oxide metabolism, Microcirculation, Sepsis physiopathology, Shock, Septic physiopathology, Vascular Endothelial Growth Factor A metabolism
Abstract

Retrospective data analysis of microcirculation in septic shock was conducted. Sepsis is characterized by a severe microvascular dysfunction that persists despite fluid resuscitation and leads to multi-organ failure even after normalization of hemodynamics in response to fluid resuscitation, vasopressors and the treatment of infection. Several clinical studies suggest that microcirculatory alterations in severe sepsis are stronger predictors of outcome than global hemodynamic variables. Microvascular dysfunction under septic shock is related to: increased capillary permeability that manifests as a breakdown of the microvascular endothelial barrier (factors which may contribute to capillary leak syndrome include endogenous proinflammatory cytokines, angiopoietin 2, vascular endothelial growth factor); arteriolar hyporesponsiveness to vasoconstrictors and vasodilators, the loss of adrenergic sensitivity and tone of smooth muscle cells lining the arterioles; loss of the anti-adhesive function of endothelial surfaces; decreased density of perfused capillaries (due to several contributing factors: decreased deformability of erythrocytes and neutrophils; activation of the clotting cascade with fibrin deposition and the formation of microthrombi; dysfunction of vascular autoregulatory mechanisms by nitric oxide; enhanced functional arteriovenous shunting of the microcirculation).

Published
2015

9. Myocardial dysfunction during septic shock (review).

Author

Gamkrelidze M, Intskirveli N, Vardosanidze K, Goliadze L, Chikhladze Kh, and Ratiani L

Subjects
Calcium metabolism, Humans, Interferon-gamma metabolism, Interleukin-1 metabolism, Interleukin-2 metabolism, Interleukin-6 metabolism, Myocardium metabolism, Nitric Oxide metabolism, Shock, Septic complications, Shock, Septic metabolism, Tumor Necrosis Factor-alpha metabolism, Ventricular Dysfunction, Left complications, Ventricular Dysfunction, Left metabolism, Myocardium pathology, Nitric Oxide Synthase Type I metabolism, Shock, Septic pathology, Ventricular Dysfunction, Left pathology
Abstract

Patients with septic shock frequently develop myocardial dysfunction evidenced by severely depressed ejection fraction with ventricular dilatation, as measured by an increase in mean systolic and end diastolic ventricular volumes. The pathophysiology of myocardial dysfunction is complex and involves a multitude of factors. The current review describes individual contributing factors and mechanisms such as upregulation of proinflammatory cytokines (IL-1, TNFα, IL-2, IL-6, IFN-γ), reduced myocardial responsiveness to ß-adrenergic stimulation, elevated circulating endothelin levels, Impaired calcium uptake and release from calcium sarcoplasmic reticulum storage, and decreased calcium channel sensitivity, overexpression of inducible NOS and increased production of Nitric oxide. We also discuss possible reasons for apparently detrimental effect of NO inhibition on cardiovascular function in large clinical trials with sepsis patients.

Published
2014

10. Promoting E2F1-mediated apoptosis in oestrogen receptor-α-negative breast cancer cells.

Author

Montenegro MF, Collado-González Mdel M, Fernández-Pérez MP, Hammouda MB, Tolordava L, Gamkrelidze M, and Rodríguez-López JN

Subjects
Apoptosis drug effects, Breast Neoplasms metabolism, Catechin analogs & derivatives, Catechin pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Dipyridamole pharmacology, Drug Resistance, Neoplasm drug effects, Drug Synergism, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, MCF-7 Cells, Tamoxifen pharmacology, Breast Neoplasms pathology, E2F1 Transcription Factor metabolism, Estrogen Receptor alpha metabolism, Tamoxifen analogs & derivatives
Abstract

Background: Because oestrogen receptor α (ERα) regulates E2F1 expression to mediate tamoxifen resistance in ERα-positive breast cancer cells, we aimed to define the possible roles of ERα and E2F1 in promoting the resistance of ERα-negative breast cancer cells to 4-hydroxy-tamoxifen (4OHT)., Methods: This study utilised conventional techniques to demonstrate the effects of 4OHT on the expression of ERα and E2F1 and also examined the individual and combined effects of 4OHT with dipyridamole (DIPY) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) on the oestrogen-negative MDA-MB-231 breast cancer cell line using viability assays, Hoechst staining, MALDI-TOF mass spectroscopy, and confocal microscopy., Results: Despite the ERα-negative status of the MDA-MB-231 cells, we observed that 4OHT efficiently up-regulated ERα in these cells and that this upregulation promoted E2F1-mediated cell growth. Because E2F1 plays a dual role in cell growth/apoptosis, we designed a therapy incorporating TMCG/DIPY to take advantage of the elevated E2F1 expression in these 4OHT-treated cells. 4OHT enhances the toxicity of TMCG/DIPY in these ERα-negative breast cancer cells., Conclusions: Because TMCG/DIPY treatment modulates the methylation status/stability of E2F1, the results demonstrate that therapies targeting the epigenetic machinery of cancer cells in the presence of overexpressed E2F1 may result in efficient E2F1-mediated cell death.

Published
2014
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11. T4 bacteriophage as a phage display platform.

Author

Gamkrelidze M and Dąbrowska K

Subjects
Bacteriophage T4 chemistry, Capsid chemistry, Capsid immunology, Capsid metabolism, Escherichia coli genetics, Escherichia coli metabolism, Escherichia coli virology, Peptide Library, Vaccines, Bacteriophage T4 genetics, Bacteriophage T4 metabolism, Cell Surface Display Techniques
Abstract

Analysis of molecular events in T4-infected Escherichia coli has revealed some of the most important principles of biology, including relationships between structures of genes and their products, virus-induced acquisition of metabolic function, and morphogenesis of complex structures through sequential gene product interaction rather than sequential gene activation. T4 bacteriophages and related strains were applied in the first formulations of many fundamental biological concepts. These include the unambiguous recognition of nucleic acids as the genetic material, the definition of the gene by fine-structure mutation, recombinational and functional analyses, the demonstration that the genetic code is triplet, the discovery of mRNA, the importance of recombination and DNA replications, light-dependent and light-independent DNA repair mechanisms, restriction and modification of DNA, self-splicing of intron/exon arrangement in prokaryotes, translation bypassing and others. Bacteriophage T4 possesses unique features that make it a good tool for a multicomponent vaccine platform. Hoc/Soc-fused antigens can be assembled on the T4 capsid in vitro and in vivo. T4-based phage display combined with affinity chromatography can be applied as a new method for bacteriophage purification. The T4 phage display system can also be used as an attractive approach for cancer therapy. The data show the efficient display of both single and multiple HIV antigens on the phage T4 capsid and offer insights for designing novel particulate HIV or other vaccines that have not been demonstrated by other vector systems.

Published
2014
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12. Role of oxidative stress in pathogenesis of atherosclerosis.

Author

Gamkrelidze M, Mamamtavrishvili N, Bejitashvili N, Sanikidze T, and Ratiani L

Subjects
Cholesterol, LDL metabolism, Coronary Artery Disease metabolism, Humans, Lipid Peroxidation, Coronary Artery Disease physiopathology, Oxidative Stress physiology
Abstract

Atherosclerotic disease remains a major cause of death. Documented cases of atherosclerosis in Georgia (Caucasus) have increased by up to 40% and, moreover, the disease is occurring with increased frequency and greater severity in younger adults. Prevention of atherosclerosis as well as detection at early stages of the disease is reviewed. The authors argue that known indicators (serum cholesterol and triglycerides, blood pressure, life style factors) show up too late in the disease when damage is already extensive, still controllable to some extent, but irreversible. Imbalances in the redox status in which excess oxidation occurs or reducing power cannot be maintained (e.g. in inflammation, age, smoking, high lipid content and oxidation) creates a state in which molecular and tissue modifications progress rapidly, leading to development of lesions and full-blown atherogenesis. Oxidative stress do not replace the recognized role of lipids and cholesterol in atherosclerosis, but rather underline that role. Indeed, quantifying redox processes may well elucidate some molecular mechanisms by which lipids mediate atherogenesis.

Published
2008

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