ARID1A, Prostaglandin E2, and Its Receptor as Possible Predictors of Malignant Transformation of the Endometrium in Endometriosis.

We studied the expression of ARID1A, prostaglandin E2 synthase, and prostaglandin E2 receptor in the endometrium and ovarian, peritoneal, and intestinal endometrioid heterotopies in women with endometriosis of young and middle reproductive age. ARID1A protein is a tumor suppressor, its expression reduced in different types of cancer. Prostaglandin E2 synthase and prostaglandin E2 receptor are involved in the signaling cascade of inflammatory reactions presumably underlying the development of endometriosis. In endometrioid heterotopies, expression of ARID1A was reduced in 1.2-4.0 times, the expression of prostaglandin E2 synthase and prostaglandin E2 receptor was reduced in 2.9-5.2 times These findings suggest that ARID1A, prostaglandin E2 synthase, and prostaglandin E2 receptor can be used as predictors of malignant transformation of endometrioid heterotopies in women with endometriosis.

Skin Fibroblasts as the Object for Clinical Diagnosis of Parkinson's Disease in Persons of Different Ages.

We compared the expression of Aß42 peptide, τ-protein, and α-synuclein in the substantia nigra and skin fibroblasts of elderly and senile patients with Parkinson's disease and subjects without neuropathology. Expression of markers in the studied tissues was assessed by immunohistochemical and immunocytochemical methods. The expression of Aß42 peptide, τ-protein, and α-synuclein in the substantia nigra of elderly and senile patients with Parkinson's disease was higher by 11-31 times than in subjects without neuropathology. In skin fibroblasts of patients with Parkinson's disease, the expression of Aß42 peptide and α-synuclein was 3-14 times higher than in subjects without neuropathology, and expression of τ-protein did not significantly differ in the studied groups. Thus, immunocytochemical analysis of the expression Aß42 peptide and α-synuclein in skin fibroblasts can be a simple method of early diagnosis of Parkinson's disease in elderly persons.

Role of LIF Cytokine and CD34 Angiogenesis Marker in Non-Developing Pregnancy.

The expression of cytokine LIF (leukemia inhibiting factor) in the endometrium of women of young reproductive age with non-developing pregnancy of unknown genesis is higher than in older women and women with infection-related miscarriages by 1.26 and 1.43 times, respectively. The expression of angiogenesis marker CD34 in the endometrium of young women with non-developing pregnancy of unknown origin is 1.59 times higher and in case of endometrial inflammation 1.31 times higher than in women of the older reproductive age with the same disease. Correlation between the endometrial expression of LIF and CD34 is detected in women of the younger reproductive age with non-developing pregnancy of unknown etiology. The expression of LIF and CD34 can be used for endometrial function evaluation in women of different age with first trimester non-developing pregnancy.

Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 µg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

Effects of Lys-Glu-Trp peptide on cell-cell interactions and vascular endothelium proliferation under normal conditions and during atherosclerosis.

The molecular mechanism of atherosclerosis is based on decreased expression of signal molecules connexin (Cx37 and Cx40), vascular endothelial growth factor (VEGF), and proliferative protein Ki-67, which characterize the processes of cell-cell interactions and proliferation of vascular endotheliocytes. Lys-Glu-Trp peptide in doses of 4 and 40 µg/ml promoted recovery of Cx37, Cx40, and VEGF expression in cultured endotheliocytes from the aorta of patients with atherosclerosis, which attests to vasoprotective effects of this agent.

Peptides regulate expression of signaling molecules in kidney cell cultures during in vitro aging.

We studied the effect of polypeptide complex isolated from calf kidney and short peptides T-31 (AED) and T-35 (EDL) on the expression of signaling molecules, markers of cell renewal (Ki-67, p53), remodeling of the extracellular matrix (MMP-14), and immune response (IL-8) in primary kidney cell cultures during aging. The complex of renal polypeptides and T-31 peptide activate cell renewal processes during aging of the renal epithelium, while gelatinase MMP-14 is the target of T-35 peptide.

[Tripeptides slow down aging process in renal cell culture].

The mechanism of geroprotective effect of peptides AED and EDL was studied in ageing renal cell culture. Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence. On the basis of experimental data models of interaction of peptides with various sites of DNA were constructed. Both peptides form most energetically favorable complexes with d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of peptides AED and EDL with DNA is the cause of gene expression, encoded marker of ageing in renal cells.

[The role of gastric APUD system in progression of chronic Helicobacter gastritis].

The study included 60 patients with chronic Halicobacter gastritis (30 with chronic non-atrophic and 30 with atrophic Halicobacter gastritis (CNAHG and CAHG)). The control group was comprised of 15 practically healthy subjects. The aim of the work was to elucidate the role of Helicobacter infection, disturbances of regeneration, endothelin-1 and melatonin-secreting neuroendocrine cells of gastric antrum in progression of chronic Helicobacter gastritis (CHG). It was shown that CHG is due to H. pylori persistence and that patients with CNAHG undergo grade III microbial contamination while in CAHG patients atrophic changes are accompanied by metaplasia of gastric mucosa (GM) and inflammation of different severity. Patients with CNAHG has an increased number of melatonin-positive gastric cells and enhanced apoptotic activity of GM epitheliocytes. Patients with CAHG experience a reduction of melatonin-positive cells correlated with enhanced apoptotic activity of GM epitheliocytes. The number of endothelin-1 positive cells in patients with CNAHG and CAHG was similar to that in controls. Adequate eradication promoted normalization of the number of gastric endothelin-1 and melatonin-secreting neuroendocrine cells in patients with CHG. The apoptotic index reached the control value within 1 month after eradication in CNAHG patients but remained relatively high in CAHG patients.

Peptidergic regulation of expression of genes encoding antioxidant and anti-inflammatory proteins.

Geroprotective peptide T-34 regulates the expression of mRNA for various genes. The development of gastric ulcer is associated with morphological and molecular changes resulting from modulation of the synthesis of antioxidant and anti-inflammatory proteins. Peptide T-34 normalizes the synthesis of these proteins by regulating the expression of the corresponding genes.

[Morphological features of placenta and expression of collagen-6, MMP-1 and TIMP-1 in placental membranes of women with premature rupture of membranes].

Morphological and immunohistochemical investigation of the women's afterbirth with premature rupture of membranes (PROM) and well-time ruptures of placental membranes has been carried out. Inflammatory infiltration of membranes and placental deficiency were higher at patients with PROM. The absence of inflammatory changes in placental tissue during growth of anhydrous gap was demonstrated. The optical density and square of MMP-1 expression were higher and TIMP-1 was lower in membranes of PROM-group than in the control one. No significant changes were found in expression of collagen-6.

[Neuroimmunoendocrine effects of ethanol in the development of pathology of internal organs].

Neuroimmunoendocrinology is a new science studying the interplay between major regulatory systems (nervous, endocrine, and immune) mediated through regulatory (signal) molecules. Its applied aspects concern elucidation of the influence of various exogenous factors on the organism manifested as alteration of signal molecule homeostasis. Effects of ethanol on organ systems are considered from the standpoint of neuroimmunoendocrinology.

[The role of epitheliocytes secreting vascular endothelial growth factor, pancreatic polypeptide and glucagon in the development of oncological diseases of the stomach].

The present study included 104 patients with gastric disorders associated with Helicobacter pylori infection. Thirty of them presented with chronic atrophic gastritis (CAG), 30 with gastric ulcer (GU), 20 with adenomatous gastric polyps (AGP), and 24 with gastric cancer (GC). The control group was comprised of 12 practically healthy subjects. We elucidated the role of vascular endothelial growth factor (VEGF) and endocrine cells of gastric mucosa producing glucagon (GC) and pancreatic polypeptide (PPP) in the patients with GAG, GU, AGP and GC prior to and after the surgical intervention and following eradication therapy. It was shown that GAG, AGP, and GC were associated with the persistence of Helicobacter pylori infection and accompanied by hyperplasia of GC and PPP-secreting endocrine cells of gastric mucosa. GU was characterized by hypolasia of VEGF-secreting epithelial cells of the stomach and GC and PPP-secreting endocrine cells of gastric mucosa. The levels of VEGF, GC and PPP that directly or indirectly realize their pathological properties through H. pylori, Bcl-2, and proapoptotic protein BAX proved to be of high prognostic value as regards the evolvement and clinical course of gastric disorders associated with Helicobacter pylori infection. The study demonstrated that adequate eradication therapy in patients with H. pylori-associated diseases of the stomach significantly reduces the number of gastric cells secreting VEGF and has practically no effect on the amount of GC and PPP-producing endocrine cells of gastric mucosa.

[The influence of melatonin included in the combined treatment of antichelicobaterial therapy on immunohistochemical characteristics of gastric epitheliocytes from patients with duodenal ulcer].

The study included 100 patients with duodenal ulcer (DU), 30 with chronic non-atrophic gastritis (CNAG), 30 with chronic atrophic gastritis (CAG) and 12 practically healthy subjects. All patients with DU and CNAG had morphologically confirmed H. pylori infection. The patients with DU were divided into 2 groups each including age-matched subjects with endoscopically, morphologically, immunohistochemically identical characteristics. Those of group 1 underwent eradication of H. pylori by a traditional 7-day procedure including the use of omeprazole (20 mg BID), claritromycin (500 mg BID) and amoxicillin (1000 mg BID). In group 2 this scheme was supplemented by melatonin (3 mg before bedtime). Patients of group 1 continued to use omeprazole and those in group 2 omeprazole + melatonin till the end of the second month. Healthy subjects and patients with CAG served as controls. All patients underwent FGDS on weeks 2 and 4, immunohistochemical study was conducted to detect endothelin-1 and melatonin-positive cells, apoptotic activity of mucosal epitheliocytes from gastric antrum was determined before and 6 weeks after the onset of therapy. It was shown that introduction of melatonin in the scheme of eradication therapy increases efficacy of H. pylori elimination and accelerates DU cicatrization. Two-month therapy with omeprazole + melatonin more effectively normalizes immunohistochemical parameters (endothelin-1 and melatonin-positive cells) and epitheliocyte apoptotic activity, than omeprazole alone.

[Hepatic encephalopathy and colon pathology in liver cirrhosis].

RESEARCH OBJECTIVE: to define a role of structural and functional changes of a colon, expression indicators of epithelial cells of mucous coat of colon that produce serotonin and hromogranin-A at in encephalopathy development at liver cirrhoses. We have examined 146 patients with liver cirrhosis of various classes using the clinical, endoscopic, morphologic and immunohistochemical methods. It is established that with increase of a class of a cirrhosis frequency of revealing of a hepatic encephalopathy, structural changes, degree dysbacteriosis of a colon. Progressing of a hepatic encephalopathy at liver cirrhoses associates with development destructive and atrophic changes of a mucous membrane of a colon and a dysbacteriosis. The increase in the morphometric rates of epithelial cells of mucous coat of colon that produce serotonin and hromogranin-A at liver cirrhoses plays a part in development of a manifesting of a hepatic encephalopathy.

[Ovary: ontogenesis and aging].

The neuroendocrine mechanisms of development and aging of ovary as the main reproductive organ are considered in the review. There are the analysed data of new investigation which is connected with the role of immune cells of ovary at involutive processes in reproductive system.

[Single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging].

The expression of matrix metalloproteinase 2 and 9 in thymus and pineal gland has been verified. These data demonstrate single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging.

[Remodelling extracellular matrix in pineal gland at aging].

Matrix metalloproteinases (MMP) 2 and 9 has been verified in pineal gland, where MMP take part in remodelling extracellular matrix. Descrease of number MMP2 and 9 has been verified in pineal gland of old age and long liver people in comparison with middle age people. Pinealocytes and/or immune cells of pineal gland can synthesize matrix metalloproteinases.

[Changes of thymocyte differentiation, proliferation and apoptosis induced by syntetic peptides].

The changes in the processes of differentiation, proliferation and apoptosis were studied in the culture of human cortical thymocytes after cell exposure to T-32 and T-38 bioregulator peptides. T-32 and T-38 peptides were shown to enhance the differentiation of immature cortical thymocytes (CD4+CD8+) into T-regulatory cells by increasing their proliferate activity and decreasing the level of apoptosis. Moreover, these peptides were found to stimulate the proliferative and antiapoptotic activity of mature T-regulatory (CD4+CD25+) cells.

[The role of matrix metalloproteinases in human thymus aging].

The use of immunohistochemical method enabled to obtain for the first time expression ferments of extracellular matrix MMP2 and MMP9 in human thymus. Expression of matrix metalloproteinases is discreased in thymus of old age people in comparison with middle age people. These data testify to the important role of metalloproteinases 2 and 9 in extracellular interaction and proliferation activity in thymus aging.

[Characteristics of the pineal gland and thymus relationship in aging].

The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.