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Khadjibaev Abdukhakim Muminovich, Phd, ScD, Professor, Director General, Republic Research Center of Emergency Medicine, Tashkent, Uzbekistan, E-mail: [email protected] Baybekov Iskander Mukhamedovich, PhD, ScD, Professor, Republic Specialized Centre of Surgery named after acad. V. Vakhidov, Head of Pathologic Anatomy Laboratory, Tashkent E-mail: [email protected] Pulatov Dilmurod Tuhtabaevich, Senior scientific researcher, Republic Research Center of Emergency Medicine, Tashkent, Uzbekistan, E-mail: [email protected]
Barrier-protective complexes of duodenum and their role in initiation and persistence of duodenal ulcers
Abstract: Aggression factors provoking epithelial level barrier complex disorder make possible the micro-organisms penetration and infiltration in deep layers of aggression factors components. It leads to development of pathologic reactions, inflammatory injuries of tissues and formation of micro-collectors which makes possible deeper penetration to stratum of duodenum and stomach wall. All above mentioned leads to appearance of peculiar circulus vituosus which is a structural base of persisting and chronization of gastroduodenal ulcers, development of their complications.
Keywords: gastroduodenal ulcers, barrier-protective complexes, Aggression factors, stomach, duodenum.
One the most important functions of gastrointestinal tract's (GIT) mucous membrane is barrier-protective one which is an important chain of unique process directed to saving of internal environment's constance [2-7; 11; 12].
W. A. Walker [12] divides GIT protective factors into non-im-munological (local intestinal flora, secretions, gastric barrier, gastric motor activity), liver filtrational capacity, antibacterial substances: lysozyme, bile acids and others) and immunological or local immune system.
B. T. Ivashkin et al. [7] define two protection lines: the first is mucous layer produced by cells and the second one — the cells themselves.
Droy et al. [11] divide protective lines into pre-epithelial, epithelial and post-epithelial. They note that mucus, immunoglobulins, saprophytic micro-flora are the components of pre-epithelial protection (including lysozyme, lactoferrin, bacteriostatin and other substances). Saprophytes locating on the enterocytes surface protect them from dehydration, adsorb macromolecules, neutralize physical and chemical aggressines, promote protection from pathogenic microorganisms and their toxins. Epithelial line, by their data, abdicates from glycocalix, epithelial membranes and connective complexes.
The authors pointed that blood flow in mucous membrane besides trophic function provides the post- epithelial protection as well.
The scheme of protective barrier reported by M. T. Droy et al. [11] from morphologic point of view does not include many components providing barrier-protective function.
Investigations underwent on extensive clinical and experimental material covering a broad range of digestive tract different pathologies allowed to characterize in detail the structures of barrier-protective functions in correlation with each other [2-6].
There were defined three levels of protection: luminal, epithelial and connective-tissue [3-6].
Luminal level. From morphologic point ofview it is presented by components of over-epithelial mucous layer having strict structural organization. It is made up from special cells secretions (mucus, pepsin, biologically active substances and others), from migrated epithelial and connective-tissue cells and from parietal micro-flora. Luminal level has an ability of self-regulation but it mostly depends on epithelial layer's conditions.
Epithelial level has been formed by epithelial lining structures. Epithelial cells with their intercellular connective complexes and intercellular spaces, intraepithelial lymphocytes, immunocompetent
Barrier-protective complexes of duodenum and their role in initiation and persistence of duodenal ulcers
cells and basic membrane refer to them. Condition of this level depends mainly on secretory activity of epithelial cell, lytic ability of their intercellular structures and the level of plasmatic membranes development. The role of intraepithelial immunocompetent cells has been described in details [1, 12]. Basic membrane besides of trophic and supporting functions has selectivity to let through various substances and micro-organisms.
Connective-tissue level consists of: basic intercellular substance; fibers and fibroblasts (non-specific passive phase); cells synthesizing non-specific protective factors — bioactive (eosinophil, mast cells); cells responsible for phagocytosis (micro- and macrophages); cells synthesizing specific protective facrors — antibodies (plasmatic cells); micro-vessels walls structures (pericytes, basic layers, endothelial cells).
Change of cells morphologic conditions reflects the condition of protective barrier [3-6].
Any disturbance of structures' continuity and in the first place, epithelial lining providing the most important level of barrier-protective function is the base of aggressines penetration into deeper complexes and development of pathologic process. The role of he-licobacters in appearing and persisting of gastroduodenal ulcers is the most bright example [5].
A. M. Khadjibaev et al. showed the presence of so called micro-collectors in the depth of gastroduodenal ulcers which are the base of their chronization and persisting [10]. This phenomenon has been registered as discovery — "Appearance of gastric juice through ulcerous defect in the stomach wall and in duodenum in patients with ulcerous disease" - № OT -12119, priority of discovery 06.02.1991.
Trigger of appearance and development of ulcerous defect and forming micro-collectors is a disorder ofbarrier complexes of stomach and duodenum mucous membrane. In the first place it refers to epithelial lining integrity disorder. It is conditioned by activation in luminal and parietal levels of aggression factors. These factors are made up as well from the presence of pathogenic micro-organisms in the lumen as activation of producing pepsinogen and hydrochloric acid [5].
But the bases of these initial injuries of epithelial lining at persisting, especially complicated by bleeding or perforation of duodenal ulcers have not been studied.
Goal: to estimate the integrity of duodenum epithelial lining at duodenal ulcers and their complications - perforations and bleedings.
Materials and methods
Biopsy materials received from dissected duodenal ulcers during surgeries and endoscopic investigations. There were 12 long-acting persisting not complicated ulcers, 18 complicated perforations and 22 with ulcerous bleedings and also control group (10 without pathologies of digestive tract) among them.
For light microscopy the samples were fixed in 10-12 % solution of neutral formalin. After appropriate processing the pieces were poured into paraffin cuts by 5-7 mcm. thickness were prepared. General morphologic picture has been studied on cuts colored by hematoxylin and eosin.
For transmission microscopy biopsy materials immediately after excision were fixed in 2.5 % solution of glutar aldehyde on phosphate buffer during 2-12 hours, washed in phosphate buffer, fixed in 1 % solution of osmium tetroxide and after dehydration in alcohol-acetone, poured into mix of epon and araldit.
Ultra slim cuts were prepared from received blocks on Ultracut (Reichert Yong) ultramicrotome which were contracted by solutions of uranylacetate and lead citrate (Ultrastainer LKB micro-processor) and were investigated on Hitachi-H-600 electronic microscope.
Investigation and photographing ofpreparations have been done with the help of Axioscope (Carl Zeiss) microscope with ProgRess, CapturePro 2.6 digital camera connective with Pentium IV PC.
Results and discussions
Undergone investigations showed integrity of mucous membrane, its epithelial lining in all investigated samples of the control group (fig. 1 2).
Fig. 1. Fringe with uninjured epithelial lining. Control G-E 10 x 10
Fig. 2. Uninjured epithelial lining of fringe.
Control G-E 10 x 40
At complicated ulcers (both perforated and bleeding) there is a disorder of epithelial lining integrity disorder with increasing mucus layer on its surface. Connective tissue cells and micro-organisms migrated from epithelial lining have been detected in mucus (fig. 3-5).
Fig. 3. Epithelial lining integrity disorder of fringe. Bleeding in stroma. Periulcerous zone of bleeding ulcer. G-E 10 x 40
Fig. 4. Epithelial lining integrity disorder of fringe. A big quantity of connective tissue cells on surface. Bleeding in stroma. Periulcerous zone of bleeding ulcer. G-E 10 x 40
Fig. 5. Mucus layer thickening with micro-organisms over epithelial lining with damaged integrity near border of perforated duodenal ulcer. Phagocytosis by neutrophil of microorganisms. G-E 10 x 40
Epithelial lining integrity disorder leads to cells of connective tissue migration increase into lumen including neutrophilic leukocytes and an ability of phagocytosis in luminal level of barrier-protecting complex. From the other side, epithelial level integrity disorder leads to a possibility of penetration different aggression factors deep into mucous membrane including pepsin, the other components of gastric juice and stomach content including microorganisms. These factors action leads to disintegration of intercellular contacts and junctions. Connective complexes are broken, intercellular fissures are dilated (fig. 6).
Fig. 6. Border of perforated duodenal ulcer. Dilatation of intercellular spaces, mitosis. TEM x 5000
Contact of various micro-organisms including fungi with cells surface leads to alteration which aggravates epithelial level integrity disorder (fig. 7, 8). Different micro-organisms including those ones which are similar to helicobacters penetrates intercellular spaces (fig. 8).
Aggression factors provoking epithelial level barrier complex disorder make possible the micro-organisms penetration and infiltration in deep layers of aggression factors components. It leads to development of pathologic reactions, inflammatory injuries
of tissues and formation of micro-collectors which makes possible deeper penetration to stratum of duodenum and stomach wall. All above mentioned leads to appearance of peculiar circulus vituosus which is a structural base of persisting and chronization of gastro-duodenal ulcers, development of their complications.
Fig. 7. Fungi like Candid on surface of epithelial cells of bleeding duodenal ulcer. TEM x 5000
Fig. 8. Micro-organisms on surface of epithelial cells, border and of intercellular spaces of bleeding duodenal ulcers. TEMx15000
Conclusion
According to data received at present study it is possible to offer an algorithm of appearing, development and persisting of ulcers:
1.
2.
3.
Aggression factors provoke epithelial level barrier complex disorder and it make possible penetration and infiltration of micro-organisms into deep layers of the other components of aggression factors.
Epithelial level barrier complex disorder leads to development of pathologic reactions inflammatory injuries of tissues and formation of micro-collectors. It makes possible deeper penetration to stratum of duodenum and stomach wall. All above mentioned leads to appearance of peculiar circulus vituosus which is a structural base ofpersisting and chronization ofgastroduodenal ulcers.
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Baybekov I. M., Mavlyan-Khodjaev R. Sh., Irsaliev Kh. I. Interaction of endogenous parietal micro-organisms of mucous membrane of digestive tract//Arch Pathol. - 1992. - 5: 18-24.
Baybekov I. M., Mavlyan-Khodjaev R. Sh. Interaction of Campylobacter pyloridis the other membrane micro-flora and stomach epithelial cells at gastroduodenal ulcers and vagotomy//Arch Pathol. - 1998. - 12: 51-54.
Baybekov I. M.,.Butaev A. Kh. Changes of barrier-protective complex structures of digestive tract at pathologic conditions. Materials of the 16th Russian gastroenterologic week. - Moscow, 2010.
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The contribution of polymorphism C634 n of gene VEGFA in development of cerebral vascular pathology in the patients...
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Khalimova Khanifa Mukhsinovna, Professor of the department neurology of Tashkent medical academy, MD, professor Rakhmatullaeva Gulnora Kutbitdinovna, PhD, Independent competitor of the department neurology
of Tashkent medical academy
Karimov Khamid Yakubovich, Professor of the department neurology of Tashkent medical academy, MD, professor
Boboev Kadir Tuxtabaevich, Professor of the department neurology of Tashkent medical academy, MD, professor E-mail: [email protected]
The contribution of polymorphism 0634 G of gene VEGFА in development of cerebral vascular pathology in the patients with cephalalgic syndrome
Abstract:
Objective. The purpose of research is to study the importance of allele variants of polymorphism C634G of gene VEGF A in the development of the cerebro-vascular pathology.
Materials and methods of research. Materials and methods of research: There were studied 178 patients who form the main group receiving out-patient and stationary treatment in the Republican Clinical Hospital № 1. The control group consisted of 172 conditionally healthy persons of the Uzbek nationality.
Results. during the comparative analysis of frequency of distribution of the alleles and genotypes of polymorphism of gene VEGF A C634G.
Conclusion. Besides the frequency of unfavourable state was defined by homozygotic genotype G/G. Keywords: cerebral vascular pathology, cephalalgic syndrome, polymorphism C634G of gene VEGFA.
The headache being multidisciplinary problem, reduce the quality of life of patients and result in significant burden to the economy of many countries in the world. Many factors have a great importance in the development of headaches, among them the special place is occupied by the pathology of the cerebral vessels. The more researchers have become interested in studying of this pathology over the last time. The molecular-genetic mechanisms of the development of the cerebral vessels underlie this pathology. Thus, one of the factor regulating the processes of the angiogenesis appeared to be vasculoendothelial grows factor (VEGF), which, first of all, has ability to induce angiogenesis and vasculogenesis. VEGF was isolated in 1989 by French doctor N. Ferrara, who was the first taking attention on its contradictory and dual role in the human body [1; 2; 3; 4]. Now it is shown, that VEGF, playing the important role in maintenance of endothelial stability and physiological neoangiogenesis, simultaneously take an active part in processes of neovascularization in the pathological situations, particularly, in the grow of atherosclerotic patch and neoplastic processes at oncogenesis [3; 7; 8; 9; 10]. The further study of VEGF role is considered perspective in relation to development of cardio-vascular diseases in the basis of which the processes of circulation disorders and ischemia lay (ischemic heart disease, disturbances of peripheral blood circulation, disorders of cerebral, retinal blood flow. The main ways of angiogenesis stimulation include stimulation of the proliferation
of endothelial cells; increase in permeability ofvessels and regulation of the production of matrix metalloproteinase [1; 2; 3; 4; 5; 6; 11].
Among several allele variants of this gene the variant VEGFA C634G gains the special importance, because the replacement of nucleotide citozine by guanine in the position 634 occurs if it is available.
The purpose of research is to study the importance of allele variants ofpolymorphism C634G of gene VEGFA in the development of the cerebro-vascular pathology.
Materials and methods of research: There were studied 178 patients who form the main group receiving out-patient and stationary treatment in the Republican Clinical Hospital № 1.
The diagnosis in the patients was made on the basis of clinical-neurologic, neurovisualized examinations: CT of the brain with angiography or MRI of the brain with angioregimen, Molecular-genetic investigation of polymorphism C634G of gene VEGFA (rs 2010963) was also carried out.
The control group consisted of 172 conditionally healthy persons of the Uzbek nationality.
Genom DNA from the samples of peripheral blood (Vacu-tainerBectonDickinsonlnternationalc EDTA) was isolated with use of kits "QIAamp DNA BloodMiniKit", Qiagen (Germany), according to the instruction. Concentration and cleanliness of DNA were estimated on the spectrophotometer NanoDrop 2000
