Influence of quercetin on morphological changes in rats testes after 180 days during central deprivation of luteinizing hormone

A relevant and popular area of research is the protective effect of the bioflavonoid quercetin, which makes it possible to use it to correct testicular dysfunction of various origins. The aim of the study was to determine the effect of quercetin on the microscopic organization of rat testicles, nitric oxide production and the intensity of oxidative stress in rat testicles on the 180th day of the experiment, during experimental central deprivation of luteinizing hormone synthesis caused by triptorelin solution. The experiment was performed on 20 adult male white rats. Rats were divided into 2 groups of 10 animals in each group: control group (I), group with central deprivation of LH synthesis + quercetin (II). Animals from the group with central deprivation of LH synthesis were injected subcutaneously with triptorelin acetate at a dose of 0.3 mg of active substance per kg and quercetin 100 mg per kg of body weight 3 times a week, while the control group was injected with saline. Ultrathin sections made by ultramicrotome were contrasted with 1 % aqueous uranyl acetate and lead citrate according to the Reynolds method and examined by electron microscopy. According to standard methods, the material was poured into paraffin blocks, from which sections with a thickness of 4 μm were made and stained with hematoxylin and eosin. Histological specimens were examined using a Вiorex 3 light microscope with a digital microfilter with software adapted for these studies. All biochemical studies were performed in 10 % of testicular tissue homogenate using a Ulab 101 spectrophotometer. Statistical processing of the study results was performed using Microsoft Office Excel software and Real Statistics 2019 extension. The nonparametric Mann-Whitney test was used to determine the statistical significance of differences between groups. Our study of the interstitial space in the testes of white rats showed the heterogeneity of populations of endocrinocytes and macrophages and the variability of structural and functional parameters. In the tissues of the testes in conditions of prolonged central deprivation of testosterone synthesis develops oxidative stress, which on the 180th day of the experiment leads to the development of edema of the interstitial space, followed by tissue fibrosis. Changes in the polarization of macrophages in our opinion may cause oxidative stress in the testes, as evidenced by increased iNOS activity and decreased arginase activity, but use of quercetin protects rat testicular tissue from oxidative damage caused by triptorelin by increasing direct antioxidant system and effects on the lipoxygenase pathway of arachidonic acid metabolism.

DEVELOPMENT OF A MATHEMATICAL MODEL OF LIVER FILTRATION

Клетки печени занимают центральное место в реакциях промежуточного метаболизма. Печень принимает участие в метаболизме почти всех классов веществ. Основной структурной единицей печени является печеночная долька, которая представляет собой призму размером 1,5-2 мм с плоскими основанием и вершиной. По всей дольке также распределены лимфатические сосуды, которые активно поглощают интерстициальную жидкость и выводят ее с регулируемой скоростью, однако зависимость скорости поглощения от интерстициального давления и других параметров известна не полностью. В работе представлена математическая модель для оценки кровотока в печеночной дольке. Рассмотренная клеточная модель включает в себя производство и прохождение лимфы по двум основным путям: поглощение лимфатическими сосудами и выход из печени через поверхность дольки в интерстициальное пространство. Приведены геометрические и механические допущения модели и ее недостатки. В биологической модели исследовано влияние изменений кровяного давления в печени на выработку лимфы и оценивается скорость поглощения лимфы и поток жидкости (как лимфы, так и крови) по всей поверхности печени. В математической модели показана классификация: статическая (не зависящая от времени), пространственная, детерминированная, нелинейная, непрерывная. Результаты исследования показали, что предлагаемая клеточная модель микроциркуляции печени включает в себя производство и прохождение лимфы по двум основным путям: поглощение лимфатическими сосудами и выход из печени через поверхность дольки в интерстициальное пространство. Выявлены основные недостатки разрабатываемой модели Liver cells are central to intermediate metabolic reactions. The liver is involved in the metabolism of almost all classes of substances. The main structural unit of the liver is the hepatic lobule, which is a prism 1.5-2 mm in size with a flat base and apex. Lymphatic vessels are also distributed throughout the lobule, which actively absorb interstitial fluid and remove it at a controlled rate, however, the dependence of the rate of absorption on interstitial pressure and other parameters is not fully known. The paper presents a mathematical model for assessing blood flow in the hepatic lobule. The considered cellular model includes the production and passage of lymph through two main pathways: absorption by the lymphatic vessels and exit from the liver through the surface of the lobule into the interstitial space. Geometric and mechanical assumptions of the model and its disadvantages are presented. A biological model investigates the effect of changes in liver blood pressure on lymph production and estimates the rate of lymph absorption and fluid flow (both lymph and blood) over the entire surface of the liver. The mathematical model shows the classification: static (independent of time), spatial, deterministic, nonlinear, continuous. The results of the study showed that the proposed cellular model of liver microcirculation includes the production and passage of lymph through two main pathways: absorption by the lymphatic vessels and exit from the liver through the surface of the lobule into the interstitial space. The main shortcomings of the developed model are revealed

Quantitative analysis of macroscopic solute transport in the murine brain

Background Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE-MRI) experiments have long reported solute transport in the brain that appears to be faster than diffusion alone, but this transport rate has not been quantified to a physically relevant value that can be compared to known diffusive rates of tracers. Methods In this work, DCE-MRI experimental data is analyzed using subject-specific finite-element models to quantify transport in different anatomical regions across the whole mouse brain. The set of regional effective diffusivities ($$D_{eff}$$ D eff ), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity ($$D_{app}$$ D app ), the known rate of diffusion through brain tissue, to draw conclusions about dominant transport mechanisms in each region. Results In the perivascular regions of major arteries, $$D_{eff}$$ D eff for gadoteridol (550 Da) was over 10,000 times greater than $$D_{app}$$ D app . In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, $$D_{eff}$$ D eff was 10–25 times greater than $$D_{app}$$ D app . Conclusions The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 1000) and significant to large molecules (> 1 kDa) in the combined interstitial space and perivascular space of smaller vessels (not resolved by DCE-MRI). Importantly, this work supports perivascular convection along penetrating blood vessels.

Management of patients with fibrosing interstitial lung diseases

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone. Summary The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature—infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis–associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, pulmonary vasodilators) lack efficacy or cause harm. Conclusion With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients.

Myogenic contractions of a somatic muscle powers rhythmic flow of hemolymph through Drosophila antennae and generates brain pulsations

Hemolymph is driven through the antennae of Drosophila melanogaster by the rhythmic contraction of muscle 16 (m16), which runs through the brain. Contraction of m16 results in the expansion of an elastic ampulla, opening ostia and filling the ampulla. Relaxation of the ampullary membrane forces hemolymph through vessels into the antennae. We show that m16 is an auto-active rhythmic somatic muscle. The activity of m16 leads to the rapid perfusion of the antenna by hemolymph. In addition, it leads to the rhythmic agitation of the brain, which could be important for clearing the interstitial space.

Quantitative Analysis of Macroscopic Solute Transport in the Murine Brain

Background: Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE) MRI offers a whole-brain view of transport and the potential for quantitative analysis to determine fundamental transport parameters. However, few DCE-MRI studies have utilized this potential, instead reporting parameters with arbitrary units disconnected from fundamental transport processes. Methods: In this work, DCE-MRI experimental data is combined with subject-specific finite-element models to quantify transport parameters in different anatomical regions across the whole mouse brain. Effective diffusivity ( ), a transport parameter combining all mechanisms of transport, is determined for each region by minimizing the root mean square error between simulations and data. The resulting sets are compared to apparent diffusivity ( ) to draw conclusions about dominant transport mechanisms in each region. Results: In the perivascular regions of major arteries, was over 10,000 times greater than . In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, was 10-25 times greater than .Conclusions: The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 10,000) and significant to large molecules (>1 kDa) in the combined interstitial space and perivascular space of smaller arteries (not resolved by DCE-MRI). Importantly, this work supports periarterial convection along penetrating and smaller arteries.

Comparison of The Variability of Small Extracellular Vesicles Derived From Human Liver Cancer Tissues And Cultured From The Tissue Explants Based On A Simple Enrichment Method: Yield, Purity And Molecular Markers

A potential of using small extracellular vesicle (sEV) for diagnostic and therapeutic purposes has attracted great interest. Some sEVs, directly derived from various tissues, can reflect the physiological and pathological state of the organism. Currently, there are two sources for obtaining tissue-derived sEV: the interstitial space of tissues and cultivation of tissue explants. The former was obtained from tissues that were digested with enzymes and the latter was released by tissue explants. In the present study, we established a new method for the isolation and purification of sEVs from the interstitial space of human liver cancer tissue. Tissues-derived sEVs (TdsEVs) isolated by this method and cultured explants-derived sEVs (cedsEVs) were both characterized by nano-flow cytometry (NanoFCM) for concentration, size distribution and purity. These vesicles were identified and compared by transmission electron microscopy and western blot. TdsEVs have a larger particle size, higher particle concentration and purity than cedsEVs. This study establishes a simple sEV isolation and purification protocol and provides a basis for selection and reference for researches of tdsEVs and cedsEVs.

INFLAMMATION OF INTERSTITIAL CONNECTIVE TISSUE SPACE INDUCED BY LEAD ACETATE AND AMELIORATIVE AFTERMATH OF FICUSCARICAON RAT TESTIS

Objective: To observe inflammation of interstitial connective tissue space caused by Lead acetate in rat testis and ameliorative after math caused by Ficuscarica. Study Design: Laboratory based experimental study. Place and Duration of Study: Anatomy Department, Army Medical College Rawalpindi together with NIH (National Institute of Health) Islamabad, from Mar to Nov 2017. Methodology: Sprague Dawley male rats, 30 in quantity were chosen and 10 animals each partited into 3 groups. Treatments were given for 8 weeks, once daily. Group A was control group. Group B was treated with dosage of 30 mg/kg of Lead acetate. Group C was given dosage of 30 mg/kg of Lead acetate as well as 80 mg/kg of Ficuscarica. Twenty four hours after the concluding dose, animals were vivisected. For histological study, testis were fixed and stained with Haematoxylin and eosin. Interstitial connective tissue space thickness was morphometrically and assessed by SPSS version 22. A p-value <0.05 was considered significant in results. Results: Interstitial space thickness was significantly increased due to inflammation (>3 times normal) in group B in comparison to groups A and C. Thickness of space was slightly increased (<2 times normal) in group C in comparison to groups A due to reduction in inflammation. Conclusion: There was increased thickness of interstitium due to inflammation, cellular congestion and lymphocytic infiltration in rat’s testis because of lead acetate but concomitant dose of Ficuscarica protects against inflammation, venous congestion of interstitial space.

The Interstitial in Structural System in Architecture

Previous knowledge has shown a concept revealing different boundaries and relations of building spaces with its outer shell; which represent the boundaries of these spaces. This concept is called interstitial space which is based on creating an interlocution and communication within this space giving a new understanding of meaning and a new approach in archi-tectural formation. This concept of knowledge description has varied as it is linked once to its nature or again to the built environment levels whether it's architectural or urban diverged within the academic and social context, as well as the blur-ring relationship nature of this space with the structural system of the building. Therefore, the problem state of this research, which goal focuses on, is highlighted as "the urge to investigate the concept of interstitial structure characteristics". Yet the methodology of the research is based on the descriptive and analytical approach consisting of three phases; phases one is to build a theoretical framework about the characteristics of the interstitial space in architecture; second is to conduct a practical study and identify several samples of buildings vary in their structural systems (traditional, structural and space); then analyze data and identify the conclusions of which the interstitial space grows and expands physically and expres-sively with the presence of the recent constructive systems and the lack of presence of the Interstitial spaced has led to spatial differentiation and closed toward inside especially those designed parametrically and reflect it in the other tradi-tional and structural constructive systems.