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"Child`s Health" 6 (49) 2013

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Dynamics of hgf, tnf-a liver in children with chronic cholecystocholangitis under the influence of combined treatment thiotriazoline and askorutin

Authors: V. Khodan, A. Volosyanko - Department of Pediatrics, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine

Categories: Family medicine/Therapy, Pediatrics/Neonatology

Sections: Clinical researches

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The liver is an important source of some growth factors and growth factor-binding proteins. Although hepatocytes synthesize the bulk of insulin-like growth factor I (IGF-I), also other types of nonparenchymal liver cells may produce this peptide [15, 20]. To the key mediators involved in the intercellular communication in the liver belong prostanoids, nitric oxide, endothelin-1, TNF-alpha, interleukins, and chemokines, many growth factors (TGF-beta, PDGF, IGF-I, HGF), and reactive oxygen species (ROS) [15, 20-23]. Paradoxically, the cooperation of liver cells is better understood under some pathological conditions (i.e., in experimental models of liver injury) than in normal liver due to the possibility of comparing cellular phenotype under in vivo and in vitro conditions with the functions of the injured organ [27, 30].

Hepatocyte growth factor (HGF), which was originally isolated as a liver generating factor, enhances hematopoiesis [21, 22]. HGF supports the differentiation of progenitors in megakaryocyte lineage, whereas SCF supports that in myeloid lineage. Also imply that HGF acts on HSCs/HPCs as a synergistic proliferative factor combined with SCF [23].

HGF plays a direct role in the control of proliferation and differentiation of erythroid progenitor cells, which can be a long-awaited mediators of paracrine interactions between stromal and hematopoietic cells in the hematopoietic microenvironment [23].

Scientists have proved that adequate liver regeneration requires adequate increase of portal venous pressure and flow design reflects elevated levels of HGF and VEGF [20, 21]. Hepatocyte growth factor could markedly recruit bone marrow-derived endothelial progenitor cells into blood circulation [26].


The aim of our study was to investigate the influence of drugs (ascorbic acid, rutin "Askorutin") and (Thiotriazoline) to state serum levels of HGF and TNF-in children with chronic cholecystocholangitis.

Materials and Methods

The study involved 120 children with chronic cholecystocholangitis. Patients were randomized into three clinical groups.

Verified the diagnosis after a detailed clinical and instrumental examination by order of the ministries of Health of Ukraine from 29.01.2013, № 59, unified clinical protocols of medical care for children with diseases of the digestive system.

During the investigation sick children will be divided into 3 groups: group 1 - children suffering from chronic cholecystocholangitis treated with standard therapy according to the protocol of the Ministry of Health of Ukraine (n = 40); group 2 - children with chronic cholecystocholangitis patients who received standard therapy with “Askorutin” active ingredient (Rutoside 50 mg, ascorbic acid 50 mg) 1 tablet 2 times a day, every 30 minutes after eating (n = 42); group 3 - children with chronic cholecystocholangitis patients who received standard therapy "Thiotriazolin" 100 mg 1 tablet 2 times a day (n = 38), as a comparison group to be examined 30 healthy children of the same age, which will be established normal values of laboratory and instrumental performance.

Research hepatocyte growth factor and tumor necrosis factor-alpha sets performed ELISA Kit, Finland. This test is based on the method of solid-phase enzyme immunoassay. Microplate is covered by specific monoclonal antibodies to hHGF and TNF-α. The results were subjected to levels of cytokines statistical analysis.

Verification of the diagnosis of chronic cholecystit, cholangitis was performed based on clinical syndromes of disease (pain, diarrhea, intoxication syndromes) data hepatobiliary ultrasound system (thickening of the gallbladder wall and bile duct more than 2 mm, packing bile ducts, the presence of sediment and rear duct infiltration).

Results and Discussion

The authentic trend towards normalization of hepatocyte growth factor concentration in serum in children who received the treatment in Askorutin. The level of HGF in children of group II before treatment was 948,94 ± 257,29 pmol / l, and after treatment askorutin 554,74 ± 53,20 pmol / l (p <0.05) (healthy vs. 458,57 ± 59 73 pmol / L (P> 0.05). children in group III that received thiotriasolin in a complex standard therapy also noted a positive trend to a decrease in HGF, but it was slower in nature. concentration of HGF in the serum of this group of children was higher and amounted to 1115,77 ± 320,27 pmol / L before treatment and 753,27 ± 47,85 pmol / L after treatment, respectively (p <0.05). according to the survey results, the concentration of HGF in children and groups who received only standard therapy, was significantly increased after treatment and was 833,88 ± 149,52 pmol / l compared to the treatment 1006,82 ± 78,68 pmol / l (p <0.05). compared with group healthy children, the figure was 458,57 ± 59,73 pmol / l was higher in half.

Index of TNF-and the treatment was 740,63 ± 179,30 pmol / ml, and after completion of therapy Thiotriazoline - 357,99 ± 92,02 pmol / ml (p <0.05), while the biased approach the relevant levels in healthy subjects (pn>0,05). The use of standard therapy with the inclusion askorutin also led to a decrease in TNF-a (p <0.05). These results are similar to exceed specified group comparisons in children (pn>0.01). Positive dynamics stabilization indicator TNF-a as a result of standard therapy was significantly (p <0.05), however was recorded slightly slower trend to reduce its level.

1. Reduced HGF in children 2 groups compared to groups 1 and 3 may indicate a further development of changes in the functional state of the liver and reduce the regenerative activity of hepatocytes.
2. Use in the treatment schemes Askorutin, Thiotriazoline and leads to eventual stabilization level value HGF, which, in our opinion, is due to cell protective and stabilizing effect on the endothelial cells of capillaries, hepatocytes of sinusoids.   

3. When used in the treatment of Thiotriazoline, there is a stabilization of TNF-a, due to its antioxidant and cytoprotective effects.

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