Morfofunctional and Molecular Changes in Placenta and Peripheral Blood in Preeclampsia and Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications with similar risk factors. Although GDM is associated with PE, the exact mechanism underlying the association is unclear. The objective of this work was to study the morphofunctional and molecular changes in the placenta and peripheral blood in PE and GDM. Local and systemic changes in the production of several placental proteins were assessed along with markers of inflammation and metabolic disorders. Expression of placental lactogen, trophoblastic ß1-glycoprotein, placental alpha-1-microglobulin, and proteinase 3 in villi was found to change in complicated pregnancy groups. Similarity of underlying pathogenic mechanisms was demonstrated for PE and GDM.

[Clinical and morphological characteristics of the atypical placentation spectrum in the uterus]. / Kliniko-morfologicheskaya kharakteristika spektra atipichnoi platsentatsii v matke.

BACKGROUND: The concern of the global community of gynecologists and obstetricians (FIGO) regarding the increase in the number of caesarean sections has resulted in the creation of a new classification, Placenta Accreta Spectrum (PAS), which presents degrees of villus invasion into the uterine wall. OBJECTIVE: Compare the main types of atypical placentation (AP) with the stages of PAS, to supplement and unify the clinical and morphological criteria AP. MATERIAL AND METHODS: Surgical material was examined from 73 women after metroplasty (n=61) and hysterectomies (n=12) from the regions of Russia, Moscow and the Moscow region for ingrown villi and from 10 women with a typical placenta location during the first cesarean section. A targeted cutting of material from the uteroplacental region was used, at least 10-12 pieces, with further H&E and Mallory staining. RESULTS: In the classification of AP, the terms «placenta accreta¼, «increta¼, «percreta¼ should be retained. It is necessary to single out pl. previa as a separate type. Attention is focused on the need to assess the depth of villi invasion accompanied by a layer of fibrinoid, the volume of scar tissue and the degree of disorganization of the myometrial bundles, the state of the vessels in the serous membrane. A new type of AP has been proposed - a sharp thinning of the lower segment of the uterus, due to the scar failure and the pressure of the growing amniotic sac, leading to atrophy and necrosis of the myometrium. CONCLUSION: An integrated approach should be used to classify atypical placentation, taking into account not only the depth of villus invasion, but also anatomical and pathogenic factors in order to develop targeted methods of surgical treatment.

Indicators of Hypoxia Tolerance as Determined by Cellular Elements of Rat Blood.

Although hypoxia tolerance is mainly determined genetically, it is important to study individual variability of animal organisms in order to identify the factors that underlie their tolerance to hypoxic exposure. We investigated blood cell counts and coagulograms in Wistar rats as predictors allowing the animal population to be split into hypoxia-tolerant and hypoxia-intolerant individuals. The validity of the specific predictors' choice was proved by a coincidence between the population split in accordance with the detected individual parameters and the results of testing animals in a decompression chamber at a rarefaction corresponding to the "rise to an altitude" of 11500 m above sea level. Circulating blood cells were quantitatively assessed by eighteen indicators before and after hypoxic exposure. The differences between animals low-tolerant (LT), high-tolerant (HT), and medium-tolerant (MT) to hypoxia were determined by five indicators: white blood cell count (WBC), granulocyte count (Gran#), red blood cell count (RBC), reticulocyte count/percent (RTC), and mean corpuscular hemoglobin (MCH). The RBC, RTC, and MCH values in HT rats were significantly higher than in LT animals (by 1.4, 1.9, and 1.1 times, respectively). The WBC and Gran# values in HT rats were lower than in LT individuals. The hypoxia tolerance indices (HTI) were calculated using the original formula. It was established that in LT rats, the HTI ≤ 0.203, in HT rats ≥ 0.335, and in MT rats < 0.335 but > 0.203. After testing in a decompression chamber, the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) decreased, but the fibrinogen level increased. LT rats were characterized by the lowest APTT, TT, and PT values and the highest values of the fibrinogen level. Our results indicate that one of the most important mechanisms underlying a high hypoxia tolerance in rats consists in sustaining reciprocal relationships between the complex of RBC indicators, which tend to increase under hypoxia, and Gran# indicators, which tend to decrease after hypoxic exposure.

Analysis of Healing of Rat Uterine Wall After Full-Thickness Surgical Incision.

We studied the dynamics of morphological changes in the operated segment of the uterine horn of Sprague-Dawley rats during the first 2 weeks of the wound-healing process after a full-thickness surgical incision with regard to the estrous cycle phase. Morphometric parameters of injured uterine right horn were compared with those in the intact left horn of the same animal as a control of changes determined by the hormonal background. It was found that the uterine epithelium in the focus of injury was restored as soon as on day 2 after surgery under the influence of estrous cycle hormones. By day 4, the wound space was completely filled with the endometrial tissue on the side of the uterine lumen and coved by the attached adipose tissue of the mesentery on the side of the abdominal cavity. The thickness of the uterine wall and the uterine lumen differed most strongly between the operated and intact uterine horns during the first 3 days and on day 6 after surgery. The size of the healing area increased during the first three days and reached the peak value by day 3, but then decreased to minimum by day 6.

Increased Blood Concentration of IgG Degradation Products in Prostate Cancer.

For elucidation of the mechanisms of IgG binding with human plasminogen in prostate cancer patients, we propose an original ELISA on polystyrene plates with immobilized heavy and light plasminogen chains. The level of IgG bound to plasminogen heavy chain in the serum of prostate cancer patients significantly exceeded that in healthy volunteers. IgG treated with plasmin more actively (by more than 2 times) bound plasminogen heavy chain than intact IgG. These findings indicate the involvement of lysine-binding sites of plasminogen heavy chain in the interaction with the C-terminal lysine of IgG and their fragments. ROC analysis of ELISA data showed significant differences between serum samples from patients with prostate cancer and benign prostatic hyperplasia. It is hypothesized that IgG in the tumor region undergo proteolysis and their products appear in the circulation.

PO-17 - Identification of IgG bound to plasminogen in oncologic diseases.

INTRODUCTION: The binding of plasminogen (Pg) to cell receptors and extracellular ligands facilitates its activation to plasmin, which stimulates the extracellular matrix degradation, neoangiogenesis and tumor invasion. Plasmin can also degrade IgG thereby exposing C-terminal lysine residues. Previously, we have found IgG specifically bounded to Pg in the plasma of patients with malignant tumors. AIM: To identify IgG degraded by plasmin in the plasma of cancer patients. MATERIALS AND METHODS: Methods of ELISA were used for comparative research of levels of IgG bound to Pg in plasma of patients with the prostate cancer (PC, n=25) and lung cancer (LC, n=17). Plasma of healthy donors (n=29) was used as control. All patients signed informed consent for participation in this study. Affinity chromatography on Pg-sepharose was used for the quantification of IgG. Carboxypeptidase was used for remove of C-terminal lysine residues of the IgG. The program ATTESTAT was used for nonparametric analysis. RESULTS: The frequency of occurence of elevated levels of IgG to Pg in plasma was detected in 68% of patients with PC, 59% of patients with LC and only 12% of healthy women and 10% of healthy men. The quantification of antibodies in plasma samples showed that the quantity of IgG to Pg in patients with PC was 27% from the total amount of IgG and in healthy men - 9%. Treatment of diluted plasma samples with carboxypeptidase B abolished the elevated levels of IgG to Pg, as well as the specific activity of the purified IgG to Pg-sepharose. CONCLUSIONS: C-terminal lysine residues which are formed as a result of degradation of native IgG with plasmin can bind to lysine binding sites on the kringle domains of Pg. Increased levels of these degraded IgG can be marker at cancer.

Seasonal Changes in Blood Cells and Biochemical Parameters in the Mongolian Hamster (Allocricetulus curtatus).

It was shown previously that the Mongolian hamster (Allocricetulus curtatus) is a mammalian species with irregular short hibernation. The purpose of the present study was to determine how this status affects seasonal changes in the biochemical and hematological parameters in A. curtatus males under a natural temperature and light regime. It was found that a reduction in circulating white blood cells, specifically lymphocytes, neutrophils, eosinophils, basophils, and monocytes, occurred in-winter. and bilirubin levels increased in spring. These characteristics make Mongolian hamsters closer to the true hibernating species. At the same time, the character of seasonal changes in the number of red blood cells, glucose, total protein, creatinine, and albumin is closer to species with torpor.

Autoantibodies to plasminogen and their role in tumor diseases.

Plasma level of IgG autoantibodies to plasminogen was measured by ELISA in patients with benign prostatic hyperplasia (n=25), prostatic cancer (n=17), lung cancer (n=15), and healthy volunteers (n=44). High levels of IgG to plasminogen were found in 2 (12%) of 17 healthy women, in 1 (3.6%) of 27 specimens in a healthy man, in 17 (68%) of 25 specimens in prostatic cancer, in 10 (59%) of 17 specimens in lung cancer, and in 5 (30%) of 15 specimens in benign prostatic hyperplasia. Comparison of plasma levels of anti-plasminogen IgG by affinity chromatography showed 3-fold higher levels in patients with prostatic cancer vs. healthy men.