Evaluating the Developed Model of Experimental Rhinitis in Laboratory Rats: Pre-Clinical Experimental Randomized Study

Background. Among the damaging factors affecting the mucociliary system of the nasal cavity, surgical wound is of particular relevance in the practice of an otorhinolaryngologist. The clinical assessment of regeneration of the mucociliary system is associated with certain diffi culties, since the intravital morphological examination of the nasal mucosa in patients is traumatic. Therefore, the development of animal models of experimental rhinitis is considered to be highly relevant in order to study the dynamics of mucociliary pathomorphological changes and assess the epithelium regeneration.Objectives. To evaluate the developed model of experimental rhinitis in laboratory rats by studying clinical, morphological and biochemical changes in the infl ammatory process.Methods. The experimental rhinitis model was developed and tested on 60 mature male Wistar rats. All animals were randomized into two groups: experimental group #1 (n = 30) — rats in which experimental rhinitis modeling was performed and group #2 (n = 30) — control, intact animals. In the course of the experiment, the authors examined the content of CRP in blood, evaluated the differential blood cell count, and studied a morphology of the nasal septum mucosa in 2, 5, 10 days after the injury to assess the dynamics of the infl ammatory process in rats of both groups. Statistical analysis of the study results was carried out by means of Statistica 8.0 (StatSoft Inc., USA).Results. After injury, the rats from group #1 developed acute rhinitis, which was clinically manifested by the release of mucous or mucopurulent secretion from the nostrils, sneezing and scratching the nose. An increase in CRP, band and segmented neutrophils, and a decrease in lymphocytes were observed in blood of the rats from group #1 in comparison with the control group. Microscopic analysis of changes in the nasal septum mucosa showed that the acute phase of exudative infl ammation developed on the second day: vascular congestion, edema, neutrophilic infl ammatory infi ltration of the submucosal membrane were observed against the background of foci of epithelial necrosis. The proportion of lymphocytes and macrophages in the infl ammatory infi ltrate increased by the fi fth day, initial signs of restoration of epithelial tissue — the formation of an undifferentiated regenerating epithelium — appeared by the tenth day.Conclusion. The results of the study show that an adequate experimental model of acute rhinitis in laboratory animals have been obtained. An acute infl ammatory process is characterized by clinical manifestations and changes in blood parameters. Particular destructive and reparative-proliferative changes develop in the mucous membrane of the nasal septum of experimental animals as a result of a surgical wound

Синдром Такоцубо у пациентки со злокачественным новообразованием почки

RELEVANCE. The increasing availability of invasive methods for assessing the coronary vessels contributes to the growth in the diagnosis of myocardial damage in intact coronary arteries. One of the least studied diseases that mimic the course of myocardial infarction is Takotsubo syndrome, which quite often remains undiagnosed in real clinical practice. The medical and economic significance of this disease is determined by the high risk of developing life-threatening complications and the need to provide emergency specialized medical care.AIM OF STUDY. The paper presents an analytical review of scientific medical literature from the perspective of illustrating modern concepts of the most common risk factors, etiopathogenesis, diagnosis and treatment of Takotsubo syndrome. A clinical observation of a patient with verified secondary Takotsubo syndrome against a malignant neoplasm of the kidney is also presented.CONCLUSIONS. For a detailed understanding of the potential mechanisms for the development of Takotsubo syndrome, determining the most informative methods for its diagnosis, developing effective strategies for providing medical care and criteria for long-term prognosis, further large-scale studies are needed. Raising the level of awareness of doctors about Takotsubo syndrome, in turn, will allow timely detection of this disease, which will improve the prognosis for patients and minimize the economic costs of treatment. The exclusion of the possibility of overdiagnosis will also help determine the true prevalence of this disease.АКТУАЛЬНОСТЬ. Возрастающая доступность инвазивных методик оценки коронарного русла способствует увеличению случаев диагностики повреждений миокарда при интактных коронарных артериях. Одним из наименее изученных заболеваний, имитирующих течение инфаркта миокарда, является синдром Такоцубо (СТ), который в реальной клинической практике довольно часто остается недиагностированным. Медико-экономическое значение данного заболевания определяется высоким риском развития жизнеугрожающих осложнений и необходимостью оказания экстренной специализированной медицинской помощи.ЦЕЛЬ ИССЛЕДОВАНИЯ. В работе представлен аналитический обзор научной медицинской литературы с позиций иллюстрации современных представлений о наиболее распространенных факторах риска, этиопатогенезе, диагностике и лечении СТ. Также приведено клиническое наблюдение пациентки с верифицированным вторичным СТ на фоне злокачественного новообразования почки.ВЫВОДЫ. Для детального понимания потенциальных механизмов развития СТ, определения наиболее информативных методов его диагностики, разработки эффективных стратегий оказания медицинской помощи и критериев отдаленного прогноза необходимы дальнейшие масштабные исследования. Повышение уровня информированности врачей о СТ, в свою очередь, позволит своевременно выявлять данное заболевание, что улучшит прогноз для пациентов и позволит минимизировать экономические затраты на лечение. Исключение возможности гипердиагностики также будет способствовать определению истинной распространенности данного заболевания

Harnessing a High Cargo-Capacity Transposon for Genetic Applications in Vertebrates

Viruses and transposons are efficient tools for permanently delivering foreign DNA into vertebrate genomes but exhibit diminished activity when cargo exceeds 8 kilobases (kb). This size restriction limits their molecular genetic and biotechnological utility, such as numerous therapeutically relevant genes that exceed 8 kb in size. Furthermore, a greater payload capacity vector would accommodate more sophisticated cis cargo designs to modulate the expression and mutagenic risk of these molecular therapeutics. We show that the Tol2 transposon can efficiently integrate DNA sequences larger than 10 kb into human cells. We characterize minimal sequences necessary for transposition (miniTol2) in vivo in zebrafish and in vitro in human cells. Both the 8.5-kb Tol2 transposon and 5.8-kb miniTol2 engineered elements readily function to revert the deficiency of fumarylacetoacetate hydrolase in an animal model of hereditary tyrosinemia type 1. Together, Tol2 provides a novel nonviral vector for the delivery of large genetic payloads for gene therapy and other transgenic applications

Genetic Rearrangements Can Modify Chromatin Features at Epialleles

Analogous to genetically distinct alleles, epialleles represent heritable states of different gene expression from sequence-identical genes. Alleles and epialleles both contribute to phenotypic heterogeneity. While alleles originate from mutation and recombination, the source of epialleles is less well understood. We analyze active and inactive epialleles that were found at a transgenic insert with a selectable marker gene in Arabidopsis. Both converse expression states are stably transmitted to progeny. The silent epiallele was previously shown to change its state upon loss-of-function of trans-acting regulators and drug treatments. We analyzed the composition of the epialleles, their chromatin features, their nuclear localization, transcripts, and homologous small RNA. After mutagenesis by T-DNA transformation of plants carrying the silent epiallele, we found new active alleles. These switches were associated with different, larger or smaller, and non-overlapping deletions or rearrangements in the 3′ regions of the epiallele. These cis-mutations caused different degrees of gene expression stability depending on the nature of the sequence alteration, the consequences for transcription and transcripts, and the resulting chromatin organization upstream. This illustrates a tight dependence of epigenetic regulation on local structures and indicates that sequence alterations can cause epigenetic changes at some distance in regions not directly affected by the mutation. Similar effects may also be involved in gene expression and chromatin changes in the vicinity of transposon insertions or excisions, recombination events, or DNA repair processes and could contribute to the origin of new epialleles

In vivo Analysis of Choroid Plexus Morphogenesis in Zebrafish

BACKGROUND: The choroid plexus (ChP), a component of the blood-brain barrier (BBB), produces the cerebrospinal fluid (CSF) and as a result plays a role in (i) protecting and nurturing the brain as well as (ii) in coordinating neuronal migration during neurodevelopment. Until now ChP development was not analyzed in living vertebrates due to technical problems. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the formation of the fourth ventricle ChP of zebrafish in the GFP-tagged enhancer trap transgenic line SqET33-E20 (Gateways) by a combination of in vivo imaging, histology and mutant analysis. This process includes the formation of the tela choroidea (TC), the recruitment of cells from rhombic lips and, finally, the coalescence of TC resulting in formation of ChP. In Notch-deficient mib mutants the first phase of this process is affected with premature GFP expression, deficient cell recruitment into TC and abnormal patterning of ChP. In Hedgehog-deficient smu mutants the second phase of the ChP morphogenesis lacks cell recruitment and TC cells undergo apoptosis. CONCLUSIONS/SIGNIFICANCE: This study is the first to demonstrate the formation of ChP in vivo revealing a role of Notch and Hedgehog signalling pathways during different developmental phases of this process

Phoenix Is Required for Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line

In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. This second cell population has been described as having stem cell-like properties, allowing efficient hair cell replacement during embryonic and larval/fetal development of all vertebrates. However, mammals lose their regenerative capacity in most inner ear neuroepithelia in postnatal life. Remarkably, reptiles, birds, amphibians, and fish are different in that they can regenerate hair cells throughout their lifespan. The lateral line in amphibians and in fish is an additional sensory organ, which is used to detect water movements and is comprised of neuroepithelial patches, called neuromasts. These are similar in ultra-structure to the inner ear's neuroepithelia and they share the expression of various molecular markers. We examined the regeneration process in hair cells of the lateral line of zebrafish larvae carrying a retroviral integration in a previously uncharacterized gene, phoenix (pho). Phoenix mutant larvae develop normally and display a morphologically intact lateral line. However, after ablation of hair cells with copper or neomycin, their regeneration in pho mutants is severely impaired. We show that proliferation in the supporting cells is strongly decreased after damage to hair cells and correlates with the reduction of newly formed hair cells in the regenerating phoenix mutant neuromasts. The retroviral integration linked to the phenotype is in a novel gene with no known homologs showing high expression in neuromast supporting cells. Whereas its role during early development of the lateral line remains to be addressed, in later larval stages phoenix defines a new class of proteins implicated in hair cell regeneration

Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance

Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant defense responses. In this review, we summarize the latest findings on plant factors that are activated by pathogen effectors to suppress plant immunity. By looking from a different point of view into host and nonhost resistance, we propose a novel breeding strategy: disabling plant disease susceptibility genes (S-genes) to achieve durable and broad-spectrum resistance

Investigation of Integral and Differential Characteristics of Variatropic Structure Heavy Concretes by Ultrasonic Methods

The article develops methods and methodology for experimental studies of centrifuged and vibro-centrifuged concrete products of annular cross-section. They assess the real variatropy of the structure and confirm the correctness of the accepted research. An original technique for experimental studies of the variatropy of the cross-sections of vibrated, centrifuged and vibro-centrifuged concretes is proposed to determine their integral (common) and differential (differing in layers) strength and strain characteristics and deformation diagrams. It has been proved that with vibro-centrifugation it becomes possible to obtain concretes with improved structure and higher characteristics compared with centrifugation and vibration techniques. Experimental studies of the differential characteristics of centrifuged and vibro-centrifuged concretes under compression and tension revealed that the outer layer of concrete had the best characteristics after centrifugation and vibro-centrifugation, and the inner layer had the worst ones. The three-layer model of the variatropic structure for centrifuged and vibro-centrifuged concrete has been experimentally confirmed. The concrete of the outer layers had the highest strength and modulus of elasticity and the least deformability; the concrete of the inner layers had the lowest strength and modulus of elasticity and the highest deformability; and the concrete of the middle layers had average characteristics. The deformation diagrams of centrifuged and vibro-centrifuged concretes were also differentiated by layers, confirming the variatropy of the structure of such concretes. The deformation diagrams for the outer concrete layer demonstrated the highest strength; the diagrams for the inner concrete layer showed the lowest strength; and the diagrams for the middle concrete layer corresponded to mean characteristics