Modeling of Alzheimer's Disease to Study the Efficacy of Cell Therapy (Review).

We analyzed the main approaches to the modeling of Alzheimer's disease for studying the effectiveness of cell therapy. Recent advances in regenerative medicine in the field of neuroscience create prospects for the use of various cell preparations for the treatment of Alzheimer's disease. Experimental data on the use of neural stem/progenitor cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells in various models of Alzheimer's disease are presented. Of particular importance is the standardization of protocols. The use of a standardized protocol in modeling of Alzheimer's disease will allow a comparative analysis of the effectiveness and safety of treatment to identify the optimal cell preparation. The data obtained on experimental animals can form the basis for further preclinical and clinical studies of cell therapy for Alzheimer's disease.

Application of Behavioral Tests for Evaluation of an Experimental Model of Alzheimer's Disease in Female Rats.

Alzheimer's disease was modeled in female Wistar rats aged 4 months by stereotaxic bilateral injection of a synthetic peptide ß-amyloid (Aß1-42) into the hippocampus. Behavioral tests (open field, Y-maze, passive avoidance, and Morris water maze) revealed significant impairment of memory and spatial navigation 8 weeks after ß-amyloid administration. At this term, the cognitive impairments typical of Alzheimer's disease are reproduced. The experimental model of Alzheimer's disease proposed by us can be used in preclinical studies of drugs for the treatment of this pathology.

[Discussion of the immunomorphological role of interactions between mast cells and Helicobacter pylori in the gastric mucosa].

Helicobacter pylori induced gastritis accounts for 70% of cases in the structure of this pathology. Features of the long-term inflammatory reaction of the mucous membrane are directly related to the mechanisms of bacterial pathogenicity, and features of immunogenesis within narrow limits of the specific tissue microenvironment of organ structures. Mast cells appear to be one of the key players (promoters) in the regulation of the inflammatory mediator cascade and the formation of cytokine-induced expression. Possessing a wide arsenal of biologically active substances, mast cells are able to participate in the formation of the immune response and resistance of the gastric mucosa, modulating both pro- and anti-inflammatory effects. The antigen-presenting features of mast cells are of interest in terms of interaction with H. pylori and induction of mucosa bacterial colonization. The aim of study was to assess the mast cell tryptase profile of the gastric mucosa in the immunopathogenesis of H. pylori-associated inflammation. Material and methods. The study included 19 biopsies of the gastric mucosa with unknown status of H. pylori infection. Microslides were stained with hematoxylin and eosin, and Giemsa's dye for plain microscopy. H. pylori infection of the gastric mucosa was detected using the immunohistochemical method. Using double immunofluorescent labeling, localization of tryptase-positive mast cells and H. pylori strains was detected. Results. In patients infected with H. pylori (n=12), there was a significant increase in the number of tryptase-positive mast cells (177.99±30.55 vs 88.58±11.49; p<0.05) with activation of secretory pathways and release of protease into the extracellular matrix of the gastric mucosa. The quantitative parameters of mast cells in the group of patients with an undetected pathogen and signs of a chronic inflammation of the gastric mucosa were statistically significantly lower than in the group of infected patients. Co-localization of tryptase-positive mast cells and H. pylori strains (with the formation of areas of large free-lying granule accumulation around the glands with pronounced degree of H. pylori contamination) was detected in gastrobiopsy specimens, the fact evidencing their close involvement in the development of inflammatory reactions of the gastric mucosa. Conclusion. The study demonstrated the features of mast cells and H. pylori interaction revealing previously unknown aspects of gastritis pathophysiology. The data obtained contribute a valuable insight to choose a treatment strategy for H. pylori-associated gastritis.

Combined histochemical approach in assessing tryptase expression in the mast cell population.

To increase the efficiency of interpretation of mast cell's contribution to the state of a specific tissue microenvironment, it is necessary to detail the molecular composition of their secretome and analyze the pathways of degranulation. Developed method of combining immunomorphological and histochemical staining protocols contributes to the most objective detection of the integral level of tryptase expression in the intraorgan population of the skin mast cells. Novel technique for tryptase detection expands the possibilities of morphological analysis, provides researchers with additional data on the structure of the mast cell population and helps visualize the processing and cytological features and structural targets of tryptase during the development of adaptive and pathological reactions. Objective determination of the tryptase profile for organ-specific mast cell populations is in great demand in clinical practice for the interpretation of pathological processes, including inflammation and oncogenesis.

[The efficacy of radio-iodine-therapy in patients with differentiated form cancer of thyroid gland in various after thyroidectomy]. / Effektivnost' radioiodterapii bol'nykh s differentsirovannym rakom shchitovidnoi zhelezy v raznye sroki posle vypolneniia tireoidéktomii.

Results of treatment of 376 patients, ageing 18-76 yrs, were analyzed to investigate the radioiodine therapy (RITH) efficacy for the thyroid differentiated cancer depending on the term of its conduction after the operation. In patients with the thyroid gland residual tissue (THGRT) only the first course of RITH efficacy was 82.6-96.1%, the THGRT and metastases devitalization in regional lymph nodes and lungs was achieved in 72.7-81.6% of patients. The RITH courses number had constituted 2.5-6.3 at average and median summary activity for one patient--11-33.8 GBq. It was suggested that tendency for the courses number and summary activity enhancement in patients with regional and distant metastases was caused by the tumor tissue mass increase according to elongation the period of time between thyroidectomy and RITH conduction. It is necessary to determine the RITH conduction urgency, basing on the risk factors analysis.

[Analysis of efficacy of complex treatment of patients with differentiated forms of the thyroid gland cancer using distant radiation therapy]. / Analiz éffektivnosti kompleksnogo lecheniia bol'nykh s differentsirovannymi formami raka shchitovidnoi zhelezy s ispol'zovaniem distantsionnoi luchevoi terapii.

Retrospective analysis of efficacy of complex treatment, including surgical intervention, radioiodine therapy (RITH), suppressive hormonotherapy of differentiated forms of the thyroid gland cancer (DFTHGC) was done in 281 patients with positive effect of postoperative distant radiation therapy (PDRTH) application as a component of the treatment. Positive effect of therapy was estimated basing on the dynamic scintigraphy data with 131I and determination of thyroglobulin level in blood serum. The PDRTH conduction does not improve prognosis of the disease, does not lower the tumor metastasizing frequency to regional lymph nodes and remote organs and does not replace RITH. To achieve positive result in 12.8% of patients with PDRTH more than two courses of RITH were performed, enhancing so the total radiation dosage on the organism. To provide protracted nonrecurrent survival of patients with DFTHGC the radical approach is necessary, envisaging performance of thyroidectomy, the timely conduction of RITH with subsequent suppressive therapy using L-thyroxin.

[Treatment and monitoring of patients with differentiated cancer of thyroid gland]. / Lechenie i monitoring bol'nykh s differentsirovannym rakom shchitovidnoi zhelezy.

There were examined 200 patients aged from 19 to 77 years with differentiated cancer of the thyroid gland (TG). The combined treatment, which included performance of operation, radioiodine therapy and hormonotherapy, was conducted to all the patients. Total and maximum subtotal TG resection was performed in 90% patients, nonradical operation--in 10%, 23% patients were reoperated. Postoperative monitoring according to chart was done with application of dynamic scintigraphy and determination of the thyroglobuline level in the blood serum. The TG residual tissue (RT) was revealed in 61% patients and in 39%--the cancer metastases in the lymphatic nodes. RT of TG was eliminated in 86.8% patients after the first radioiodine therapy course conduction in middle remedial activity (2.79 +/- 0.11) GBq, the metastases devitalization--in 67.9% in middle remedial activity (4.07 +/- 0.12) GBq.

[Importance of scintigraphy in the evaluation of surgical treatment outcome in differentiated cancer of the thyroid gland]. / Znachenie stsintigrafii v otsenke iskhoda khirurgicheskogo lecheniia differentsirovannogo raka shchitovidnoi zhelezy.

Experience of radionuclide investigation in 493 patients with differentiated cancer of thyroid gland is summarized. The consequences due to incorrect conducting of patients with cancer after the operation were adduced on distinct examples. The program for conducting and observation of patients with thyroid gland cancer after the operation conduction was proposed directed on the early diagnosis of recurrencies and metastases, determination of indications for radioiodine therapy.

[The effect of environmental factors on the concentration of tumor markers in the blood serum and on the indices characterizing thyroid function]. / Vliianie nekotorykh faktorov okruzhaiushchwei sredy na kontsentratsiiu v syvorotke krovi opukholevykh markerov i pokazateli, kharakterizuiushchie sostoianie shchitovidnoi zhelezy.

Combined versus separate exposure of male organism to cesium-137 and chemical agents results in a more pronounced hyperferritinemia in the former case. In female chemists the ferritin level is dependent to a considerable extent on the menstrual cycle showing a tendency for the iron-containing protein level to decrease because of the action of a number of chemical agents. The rise of the level of cancer embryonic antigen is more readily seen in persons with high levels of cesium-137. Concentrations of carbohydrate antigen (CA-125) and mucin-like antigen are appreciably higher in female chemists incorporating cesium-137, and in those within the 30-km radius of the ChNPP. The level of thyroglobulin was raised in the chemists having a background incorporation of cesium, the liquidators of the aftermaths, and particularly in those happened to be in the 30-km zone. Each of the unfavourable factors taken separately (chemical agent or cesium-137) had lesser effect on the degree of elevation of TG content and hormone-forming function of the thyroid gland. An additional information has been obtained concerning the risk groups, which, however, serves as an indirect measure of carcinogenic effect various environmental factors exert on the organism.

[Changes in the beta 2-microglobulin levels of the blood serum in patients with benign and malignant neoplasms]. / Izmenenie urovnia beta 2-mikroglobulina v syvorotke krovi bol'nykh s dobrokachestvennymi i zlokachestvennymi novoobrazovaniiami.

Radioimmunological examination of beta 2-microglobulin in the blood serum of 525 patients revealed that increased protein levels were observed in patients with malignant tumours of the pancreas, duodenal papilla, ovaries, soft tissues, lymphomas. In benign diseases (pancreatitis, ovarian cysts) the beta 2-microglobulin concentration did not significantly exceed the discrimination value. Due to the low sensitivity and specificity this protein has dubious significance as a tumour marker. It is suggested that in some cases of malignant tumours changes of the beta 2-microglobulin level may be related to hepatorenal insufficiency, spread of the disease. These data may provide supplementary information on the prognosis and evolution of the tumour process after combined treatment.

[The importance of esophagoscintigraphy for assessing esophageal function in patients with digestive organ diseases]. / Znachenie ézofagostsintigrafii dlia otsenki funktsional'nogo sostoianiia pishchevoda u bol'nykh s zabolevaniiami organov pishchevareniia.

Dynamic esophagoscintigraphy is a physiological method of diagnosis of esophageal functional disorders but also for detection of gastroesophageal reflux. Esophagoscintigraphy allows to reveal functional disorders of the esophagus and inferior esophageal sphincter not only of diseases of the esophagus but also in different gastroenterological pathology and is also useful in detecting early motor disorders of the esophagus. Quantitative characteristics of the functional state of the esophagus and grade of gastroesophageal reflux permit to evaluate the efficacy and predict results of operative treatment.

[Methodologic approaches to assessing the noise level of health resorts and places of mass recreation of the population]. / Metodicheskie podkhody k otsenke shumogo rezhima kurortov i mest massovogo otdykha naseleniia.

Methodological approaches to the assessment of noise regime at health resorts and places of rest of the population were set forth when carrying out preventive and current sanitary surveillance. The sources governing the noise regime of health resorts and places of rest were identified, and the problems of zone arrangement of places of rest according to its type (long-term or short-term) analysed. Permissible noise levels were given for various functional zones and the measures for normalization of noise regime proposed.

[Scintigraphy of the normal esophagus and a tumor lesion]. / Stsintigrafiia pishchevoda v norme i pri ego opukholevom porazhenii.

Esophageal scintigraphy with labeled liquid and solid food (water solution of radioactive colloid and mixture of egg with radioactive colloid coagulated by heating) was performed in 34 patients without a history of esophageal diseases permitting qualitative and quantitative characterization of normal motor evacuatory function of the esophagus and the lower esophageal sphincter (LES). Altogether 46 patients with esophageal cancer and stomach cancer with esophageal involvement were investigated before therapy. In cancer of the esophagus its function failed with relation to a tumor site and was in direct proportion to a stage of tumor spreading. The method permitted the determination of the level of a pathological focus, a degree of esophageal permeability, quantification of a degree of esophageal dysfunction, the improvement of functional diagnosis of the esophagus and LES, and the determination of motor disorders at the earliest stages of tumor development.

[Scintigraphy in cancer of the esophagus]. / Stsintigrafiia pri rake pishchevoda.

Esophagoscintigraphy with labeled liquid and solid food was performed in 34 patients without subjective complaints and signs of disease of the esophagus in the patient history permitting the determination of quantitative and qualitative characteristics of normal motor-evacuatory function of the esophagus and lower esophageal sphincter (LES) under the most physiological conditions using mixtures of labeled natural food ingredients as compared to routine methods. In esophageal transit time (ETT) over 5 sec., a clearance value below 87.2% and passage rate below 21.6% for liquids, and ETT over 9 sec., a clearance value of 86.6% and passage rate less than 11.39% respectively for solid food disorders of esophageal and/or LES motor function were noted. Normal oropharyngeal time was 1.5-2 sec. A total of 46 patients with esophageal cancer and stomach cancer with the involvement of the esophagus before treatment were examined. In cancer of the esophagus its function depended on a tumor site and stage. In order to raise diagnostic sensitivity dynamic esophagoscintigraphy should be performed using liquid and solid food because during liquid passage a study with a hard bolus of patients with severe esophageal dysfunction showed that in 36.9% of the patients the quantitative and qualitative indices were within normal. Radionuclide methods permit the determination of the level of a pathological focus, a degree of esophageal permeability, quantitative characterization of a degree of disorder of esophageal function in order to raise the functional diagnosis of the esophagus and LES, and the determination of motor disorders at the earliest stages of tumor development.