[Changes in the type and amount of bone collagens in chronic suppurative otitis media]. / Izmenenie tipovogo i kolichestvennogo sootnosheniya kollagenov kostnoi tkani pri khronicheskom gnoinom srednem otite.

OBJECTIVE: Comparative assessment of the collagen-tissue interaction in the bone tissue of the middle ear structures in patients with chronic suppurative otitis media (CSOM). MATERIAL AND METHODS: A prospective study of 42 patients aged 16-60 years with CSOM admitted for reconstructive sanitizing surgery was performed. To study the collagen-tissue interaction, intraoperative samples of the bone tissue of the middle ear were used. A software calculation of vascular-stromal areas and ratios of various types of bone tissue collagen was carried out during histomorphological examination. RESULTS AND DISCUSSION: The quantitative and qualitative parameters of bone tissue collagen obtained intraoperatively in patients with CSOM were studied. The cavities of the middle ear are in the phase of a chronic purulent process, when the bone structures are morphologically disorganized according to the pathological type, and sclerosis with overgrowth of the cellular structure of the mastoid process is considered a favorable outcome for delimiting the focus of inflammation in the pyramid of the temporal bone. CONCLUSIONS: Changes in the processes of collagen remodeling of bone structures contribute to the maintenance of inflammation of the middle ear in all clinical forms of CSOM. Pathological osteogenesis can serve as an indicator of the progressive course of a purulent-destructive process in the cavities of the middle ear, which makes it possible to reliably determine the rate of bone tissue transformation to predict relapse after reconstructive and sanitizing surgery.

Metabolic Reprogramming of Trophoblast Cells in Response to Hypoxia.

Hypoxia of trophoblast cells is an important regulator of normal development of the placenta. However, some pathological states associated with hypoxia, e.g. preeclampsia, impair the functions of placental cells. Oxyquinoline derivative inhibits HIF-prolyl hydroxylase by stabilizing HIF-1 transcription complex, thus modeling cell response to hypoxia. In human choriocarcinoma cells BeWo b30 (trophoblast model), oxyquinoline increased the expression of a core hypoxia response genes along with up-regulation of NOS3, PDK1, and BNIP3 genes and down-regulation of the PPARGC1B gene. These changes in the expression profile attest to activation of the metabolic cell reprogramming mechanisms aimed at reducing oxygen consumption by enabling the switch from aerobic to anaerobic glucose metabolism and the respective decrease in number of mitochondria. The possibility of practical use of the therapeutic properties of oxyquinoline derivatives is discussed.

New Experimental Models of Retinal Degeneration for Screening Molecular Photochromic Ion Channel Blockers.

Application of molecular photochromic ion channel blockers to recover the visual function of a degenerated retina is one of the promising trends in photopharmacology. To this day, several photochromic azobenzene-based compounds have been proposed and their functionality has been demonstrated on cell lines and knockout mouse models. Further advance necessitates testing of the physiological activity of a great number of new compounds. The goal of this study is to propose animal models of photoreceptor degeneration that are easier to obtain than knockout mouse models but include the main features required for testing the physiological activity of molecular photoswitches. Two amphibian-based models were proposed. The first model was obtained by mechanical deletion of the photoreceptor outer segments. The second model was obtained by intraocular injection of tunicamycin to induce the degeneration of rods and cones. To test our models, we used 2-[(4-{(E)-[4-(acryloylaminophenyl]diazenyl}phenyl)amino]-N,N,N-triethyl-2-oxoethanammonium chloride (AAQ), one of the compounds that have been studied in other physiological models. The electroretinograms recorded from our models before and after AAQ treatment are in agreement with the results obtained on knockout mouse models and reported in other studies. Hence, the proposed models can be used for primary screening of molecular photochromic ion channel blockers.

[Role of dopamine as a regulator of vertebrate photoreceptors].

Numerous and profound cyclical changes in retina functioning during a 24-hour daily cycle are largely determined by the influence of two neuromodulators--melatonin and dopamine. Do- pamine and melatonin form a reciprocal pair by mutually inhibiting the synthesis of each other, and they release into extracellular space of the retina approximately in antiphase. Dopamine is cyclically synthesized by special populations of dopaminergic amacrine cells in the retina and its content increases during the day and decreases at night. Like melatonin, dopamine affects all the major cell types of the outer and inner retinal layers. Activation of dopamine D1- and D2-type receptors regulate the activity of protein kinase A and the intracellular concentration of cAMP, and may trigger other regulatory pathways, including activation of phospholipase C. In photorecep- tors, dopamine acting on D2-type receptors reduces cAMP concentration, suppresses melatonin synthesis and regulates the conduction of gap junctions between rods and cones, depending on the phase ofthe light cycle. By decreasing the concentration of cAMP, dopamine could also be a regu- lator of the phototransduction cascade and other cellular functions of the photoreceptor. Here we review some of these possibilities. Key words: dopamine, dopamine receptors, cAMP, retina, photoreceptor, circadian rhythms, protein kinase A.

[Comparative analysis of heat shock promoters efficiency in two diptera species].

Heat shock proteins (Hsp) provide cellular and whole body adaptation of animals to various adverse environmental conditions. Hsp70 is apparently the major player underlying biological adaptation in all organisms studied so far. In all animals the regulatory regions of studied heat shock genes include several conservative promoter elements HSEs (heat shock elements) that are necessary for binding of heat shock transcription factor (HSF). The promoter regions of hsp70 genes are extremely conserved and, hence, it was generally accepted that they are universal and can operate in species belonging to different phyla. In the present work we performed the comparative analysis which revealed characteristic differences in the hsp 70 promoters of two Diptera species: Drosophila melanogaster and highly thermotolerance soldier fly Stratiomys singularior. We measured promoters activity in D. melanogaster cell culture exploring in vitro luciferase reporter assay. The analysis demonstrated significantly higher strength ofD. melanogaster promoters in spite of the fact that comparable numbers of HSEs are present in both species. These drastic differences in the promoter strength are probably due to absence of GAF-binding sites, which are necessary for efficient functioning of D. melanogaster hsp70 promoters. In contrast, comparison of hsp83 promoters isolated from these two species does not show significant differences. Our results demonstrate existence of different evolutionary trends in the regulation of the hsp70 expression even within the same order (Diptera).

Novel arrangement and comparative analysis of hsp90 family genes in three thermotolerant species of Stratiomyidae (Diptera).

The heat shock proteins belonging to the Hsp90 family (Hsp83 in Diptera) play a crucial role in the protection of cells due to their chaperoning functions. We sequenced hsp90 genes from three species of the family Stratiomyidae (Diptera) living in thermally different habitats and characterized by extraordinarily high thermotolerance. The sequence variation and structure of the hsp90 family genes were compared with previously described features of hsp70 copies isolated from the same species. Two functional hsp83 genes were found in the species studied, that are arranged in tandem orientation at least in one of them. This organization was not previously described. Stratiomyidae hsp83 genes share a high level of identity with hsp83 of Drosophila, and the deduced protein possesses five conserved amino acid sequence motifs characteristic of the Hsp90 family as well as the C-terminus MEEVD sequence characteristic of the cytosolic isoform. A comparison of the hsp83 promoters of two Stratiomyidae species from thermally contrasting habitats demonstrated that while both species contain canonical heat shock elements in the same position, only one of the species contains functional GAF-binding elements. Our data indicate that in the same species, hsp83 family genes show a higher evolution rate than the hsp70 family.

Comparative morphology of laser lesion sites in parenchymal organs (liver, kidney, spleen).

The inflammatory and reparative processes in the parenchymal wounds after laser coagulation are characterized by predominance of proliferative reaction. Injury foci are always spatially separated from the intact tissue. Coagulation necrosis and thrombosis lead to suppression of the exudative component of inflammation in sites of laser exposures in the liver, kidneys, and spleen. Early macrophage response stimulates proliferation of fibroblasts and formation of the fine connective tissue scar within 14 days.

[cAMP as a regulator of the phototransduction cascade].

Until recently, it has generally been believed that cyclic AMP plays an important role in supporting circadian cycles in the vertebrate retina, but does not directly control the photoreceptors' phototransduction cascade. However, the cAMP levels in photoreceptors oscillate during the day/night cycle, and the cAMP turnover in photoreceptors may be light-dependent. Thus it is natural to suggest that the cAMP-dependent protein phosphorylation may be a mechanism of tuning phototransduction to lighting conditions. In the present review, we summarize available information on the structure and operation of the retinal pacemaker, role(s) of cAMP in its functioning, and identified intracellular targets that could be controlled by cAMP. We discuss our recent results that show that cAMP changes do regulate the phototransduction cascade. This regulation may substantially extend the range of photoreceptor's adaptation by increasing its sensitivity at night, and reducing the sensitivity in bright light.

[Experimental, morphological and clinical aspects of transmyocardial laser revascularization]. / Eksperimental'no-morfologicheskie i klinicheskie aspekty transmiokardial'noi lazernoi revaskuliarizatsii.

Experimental, pathomorphological and clinical data substantiating use of transmyocardial laser revascularisation in the treatment of coronary heart disease (CHD) are presented. It is shown that the objective criterion of clinical efficacy of transmyocardial laser revascularisation in 58 patients with CHD is an increase of myocardial perfusion due to neoangiogenesis. This leads to improvement of cardiac function and general state of the patients. Surgical intervention has no substantial influence on contractile function of left ventricular myocardium in patients with CHD.

[Clinico-morphologic results of laser myocardial revascularization in ischemic heart disease]. / Kliniko-morfologicheskie rezul'taty lazernoi revaskuliarizatsii miokarda pri ishemicheskoi bolezni serdtsa.

Transmyocardial laser revascularization was applied in 58 patients with ischemic heart disease. The objective criterion of the method efficiency was an increase in myocardium perfusion due to newly formed blood vessels under influence of laser irradiation. The laser treatment has improved cardiac function and general condition of the patients. The surgery did not exert considerable influence on the contractile capacity of the myocardium in the patients treated.

Chernobyl-related thyroid cancer in children of Belarus: a case-control study.

The accident at the Chernobyl nuclear power plant on April 26, 1986, released approximately 2 EBq of 131I and other radioiodine isotopes that heavily contaminated southern Belarus. An increase in thyroid cancer reported in 1992 and attributed to the Chernobyl accident was challenged as possibly the result of intensive screening. We began a case-control study to test the hypothesis that the Chernobyl accident caused the increase in thyroid cancer. Records of childhood thyroid cancer in the national therapy centers in Minsk in 1992 yielded 107 individuals with confirmed pathology diagnoses and available for interview. Pathways to diagnosis were (1) routine endocrinological screening in 63, (2) presentation with enlarged or nodular thyroid in 25 and (3) an incidental finding in 19. Two sets of controls were chosen, one matched on pathway to diagnosis, the other representing the area of heavy fallout, both matched on age, sex and rural/urban residence in 1986. The 131I dose to the thyroid was estimated from ground deposition of 137Cs, ground deposition of 131I, a data bank of 1986 thyroid radiation measurements, questionnaires and interviews. Highly significant differences were observed between cases and controls (both sets) with respect to dose. The differences persisted within pathway to diagnosis, gender, age and year of diagnosis, and level of iodine in the soil, and were most marked in the southern portion of the Gomel region. The case-control comparisons indicate a strong relationship between thyroid cancer and estimated radiation dose from the Chernobyl accident.

[The status of the body protective systems in children in atmospheric pollution by grain dust]. / Sostoianie zashchitnykh sistem organizma detei pri zagriaznenii atmosfernogo vozdukha zernovoi pyl'iu.

The use of noninvasive methods has revealed changes in the detoxification and immune systems in children exposed to grain dust-polluted ambient air. Impaired detoxification and immunity may be considered to be a manifestation of the common pathological mechanism responsible for reduced resistance to adverse factors and they lead to the increased risk of nonspecific infectious processes and allergy in the population.

[Experimental study of the effect of formaldehyde during embryogenesis on the activity of rat liver enzyme systems in ontogenesis]. / Eksperimental'noe izuchenie vozdeistviia formal'degida v period émbriogeneza na aktivnost' fermentnykh sistem pecheni krys v ontogeneze.

The pregnant rats were treated with formaldehyde (0.5 mg/kg daily per os) during whole period of pregnancy. The activity of cytochrome-c-oxidase, malate dehydrogenase, nucleotidase, glucose-6-phosphatase, beta-glucuronidase, N-acetyl-beta-glucosaminidase, beta-galactosidase, H(+)-ATPase, glutamate dehydrogenase, NAD- and NADP-isocitrate dehydrogenase, fructose-bisphosphate aldolase, glucose-6-phosphate dehydrogenase and content of protein in liver celts of offsprings (newborns, 2 weeks age and 2 months age) were studied. It was shown differences in development enzyme systems of control and experimental animals during ontogenesis.

Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident.

Since the Chernobyl nuclear reactor accident, a striking increase of thyroid carcinoma has been reported in children exposed to radiation in Belarus. Because of its unprecedented scale and its emotional implications, this finding has raised concern and called the attention of the scientific community to this major health problem. Although epidemiologically documented, a direct correlation between thyroid cancer and radiation exposure has not been definitely proven at the molecular level. On the assumption that ionizing radiation could cause specific and common cancer-associated genetic lesions, an analysis of oncogene activation and/or tumor suppressor gene inactivation would help to define radiation-induced thyroid carcinomas. Therefore, we have analyzed by different molecular approaches, including Southern blotting, DNA transfection assay on NIH-3T3 cells, and reverse transcription-PCR analysis, six papillary carcinomas from children living in the region of Belarus at the time of the Chernobyl nuclear accident to identify tumor-specific gene rearrangements of the proto-oncogenes RET and TRK, previously found activated in a tumor type-specific manner in papillary thyroid carcinoma. Using Southern blot analysis in four cases, we could detect specific rearranged bands indicating an oncogenic activation of RET that in three cases resulted in rearranged sequences provided by the same activating gene. Moreover, the DNA of the last three cases showed a biological activity in transforming NIH-3T3 cells after the DNA-mediated transfection assay, and the respective NIH-3T3 transfectants were found to express the oncogenic fusion transcripts. These results support the possibility that RET oncogenic activation could represent a major genetic lesion associated with thyroid carcinoma in children exposed to the Chernobyl nuclear accident.

Urinary iodine excretion in Belarus children.

Casual urine samples were collected to determine iodine excretion of 1680 Belarus children during 1990-1994. The subjects, 8-16 years old, were from nine different regions of Belarus; 60% were from the Gomel oblast, which has been associated with relatively high levels of radioiodine fallout and increased incidence of thyroid cancer. Most of the median values indicate borderline/low iodine intake or mild iodine deficiency. Ranges were wide but 163 children excreted < 20 micrograms I/l urine and they should be considered severely deficient in iodine.

[Evaluation of maximal permissible concentration of 2-allyl oxyethanol in the atmospheric air]. / Obosnovanie predelno dopustimoi kontsentratsii 2-alliloksiétanola v atmosfernom vozdukhe.

The threshold irritable concentration of 2-allyl oxyethanol (2-AOE) in ambient air was determined at the level of 0.68 mg/m3. The threshold of chronic effect of 2-AOE is 0.075 mg/m3. The mean daily permissible concentration of 2-AOE is suggested at the level of 0.01 mg/m3.