The Unmet Needs for Studying Chronic Pelvic/Visceral Pain Using Animal Models

The different definitions of chronic pelvic/visceral pain used by international societies have changed over the years. These differences have a great impact on the way researchers study chronic pelvic/visceral pain. Recently, the role of systemic changes, including the role of the central nervous system, in the perpetuation and chronification of pelvic/visceral pain has gained weight. Consequently, researchers are using animal models that resemble those systemic changes rather than using models that are organ- or tissue-specific. In this review, we discuss the advantages and disadvantages of using bladder-centric and systemic models, enumerating some of the central nervous system changes and pain-related behaviors occurring in each model. We also present some drawbacks when using animal models and pain-related behavior tests and raise questions about possible, yet to be demonstrated, investigator-related bias. We also suggest new approaches to study chronic pelvic/visceral pain by refining existing animal models or using new ones.</jats:p

Mechanisms underlying bone loss associated with gut inflammation

Patients with gastrointestinal diseases frequently suffer from skeletal abnormality, characterized by reduced bone mineral density, increased fracture risk, and/or joint inflammation. This pathological process is characterized by altered immune cell activity and elevated inflammatory cytokines in the bone marrow microenvironment due to disrupted gut immune response. Gastrointestinal disease is recognized as an immune malfunction driven by multiple factors, including cytokines and signaling molecules. However, the mechanism by which intestinal inflammation magnified by gut-residing actors stimulates bone loss remains to be elucidated. In this article, we discuss the main risk factors potentially contributing to intestinal disease-associated bone loss, and summarize current animal models, illustrating gut-bone axis to bridge the gap between intestinal inflammation and skeletal disease

A Cross-Disciplinary Examination of Institutional Diversity: How University Programs Advance a Diverse Workforce

Diversity in higher education is encouraged and celebrated throughout many predominant universities across the United States. Institutions of higher learning benefit from diversity in all aspects of campus life; from classes, organizations, or extracurricular activities. Institutional theory is applied to this study to examine how diversity programs are implemented in various university types (national research, private, and state) as well as different settings (educational opportunities, leadership, and accessibility) to develop a qualified and diverse workforce. To achieve this objective, we suggest universities implement a multifaceted approach focusing on initiatives at the university, faculty, and student level

ПОРІВНЯЛЬНИЙ АНАЛІЗ ДВОХ ВИДІВ КОНТРОЛЮ ПРИ ФОРМУВАННІ ЕКСПЕРИМЕНТАЛЬНОЇ МОДЕЛІ ХРОНІЧНОГО ВИРАЗКОВОГО КОЛІТУ

SUMMARY. The article presents a comparative analysis of two types of control in the remodeling of chronic ulcerative colitis with 2,4-Dinitrobenzenesulfonic acid (DNBS) in 50&nbsp;% ethanol solution, based on which the authors do not recommend the use of animals with intrarectal ethanol administration as the only control to prevent misinterpretation of the results. The aim – to сompare two types of control in the reproduction of an experimental model of chronic ulcerative colitis to prevent misinterpretation of the results. Material and Methods. The analysis of the presence and severity of inflammatory pathological processes in the colon by morphological method and cyclooxygenase-1 and -2 content determination by enzyme immunosorbent assay have been carried out on three groups of sexually mature laboratory rats of both sexes of the WAG population (the first control group – intrarectal administration of 0.9&nbsp;% saline; the second control group – administration of 50&nbsp;% ethanol solution; the experimental group – administration of DNBS in 50&nbsp;% ethanol solution). Results. Similar morphological patterns and changes in the content of cyclooxygenases in the colon tissue were revealed under the influence of both DNBS dissolved in alcohol and ethanol. There was no difference in these parameters between the experimental and second control groups. Conclusions. A group of animals with intrarectal administration of ethanol can not be the only control in the model of chronic ulcerative colitis, but can be used to identify effects due to DNBS as hapten and not ethanol as gut barrier “destroyer”.РЕЗЮМЕ. У статті проведено порівняльний аналіз двох видів контролю при ремоделюванні хронічного виразкового коліту за допомогою 2,4-Dinitrobenzenesulfonic acid (DNBS) у 50&nbsp;% розчині етанолу, на підставі якого автори не рекомендують використовувати тварин з інтраректальним введенням етанолу в якості єдиного контролю для запобігання некоректному трактуванню отриманих результатів. Мета – порівняння двох видів контролю при відтворенні експериментальної моделі хронічного виразкового коліту для запобігання некоректному трактуванню отриманих результатів. Матеріал і методи. На трьох групах статевозрілих лабораторних щурів обох статей популяції WAG (перша контрольна група – інтраректальне введення 0,9&nbsp;% фізіологічного розчину; друга контрольна група – введення 50&nbsp;% розчину етанолу; експериментальна група – введення DNBS у 50&nbsp;% розчині етанолу) проведено аналіз наявності та ступеня вираження альтеративно десквамативних та запальних змін у товстій кишці морфологічним методом та визначення вмісту циклооксигенази-1 та циклооксигенази-2 імуноферментним методом. Результати. Виявлено аналогічні морфологічні патерни та зміни вмісту циклооксигеназ за умов впливу як DNBS, розчиненого в спирті, так і етанолу. Різниці за цими показниками між експериментальною та другою контрольною групами не виявлено. Висновки. Група тварин з інтраректальним введенням етанолу не може бути єдиним контролем при моделюванні хронічного виразкового коліту, а може бути використана для виявлення ефектів, обумовлених саме гаптеном DNBS, а не «руйнівником» бар’єру кишечника етанолом

ОСОБЛИВОСТІ КЛІНІЧНОГО ПЕРЕБІГУ АДЕНОМІОЗУ ПІСЛЯ ПЕРЕНЕСЕНОГО ЗАХВОРЮВАННЯ COVID–19

The aim of the study – to study the clinical features of the course of adenomyosis in women of reproductive age 3 months after suffering from the COVID-19 disease. Materials and Methods. 30 women of reproductive age (24–40 years old), patients with diffuse adenomyosis of the I–IV degree, 3 months after suffering from the COVID-19 disease of varying degrees of severity, were examined. The clinical course of adenomyosis, the results of laboratory indicators were analyzed Results and Discussion. The average duration of adenomyosis from the moment of diagnosis was 7±1 years. Combined pathology occurred in 100 % of patients. Patients with adenomyosis are characterized by polymorbidity, frequent exacerbations of extragenital diseases, and polypharmacy. Gynecological pathology is represented by infectious processes of the vagina, cervix, leiomyoma, menstrual dysfunction. Diffuse adenomyosis was clinically manifested by heavy menstrual bleeding, dysmenorrhea, pelvic and headache pains, nausea, indigestion, and frequent urination. There were increased levels of platelets, monocytes, ESR, fibrinogen, D-dimer, and decreased levels of hemoglobin, erythrocytes, lymphocytes, ferritin, vitamin D. SARSCov-2 (COVID-19) IgG antibodies (positive rate) were detected in 100% of women within 1.84 – 1.90. Conclusions. Features of the clinical course of the diffuse form of adenomyosis of the I–IV degree of severity in women of reproductive age after suffering from the disease of COVID-19 consist in the activation of the symptoms of the main disease, progressive anemization of the body, and an increase in the thrombotic activity of the blood. The presented complications are a rationale for determining the personalized tactics of managing patients after a disease.Мета дослідження – вивчення клінічних особливостей перебігу аденоміозу у жінок репродуктивного віку через 3 місяців після перенесеного захворювання COVID–19. Матеріали та методи. Обстежено 30 жінок репродуктивного віку (24 – 40 років), хворих на аденоміоз дифузної форми І – ІV ступеня, через 3 місяці після перенесеного захворювання COVID–19 різного ступеня тяжкості. Аналізували клінічний перебіг аденоміозу, результати лабораторних показників. Результати дослідження та їх обговорення. Середній термін захворювання аденоміозом від встановлення діагнозу становив (7±1) року. Поєднана патологія мала місце у 100 % хворих. Хворим на аденоміоз властиві поліморбідність, часті загострення екстрагенітальних захворювань, поліпрагмазія. Гінекологічна патологія представлена інфекційними процесами піхви, шийки матки, лейоміомою, порушенням менструальної функції. Дифузний аденоміоз клінічно проявлявся тяжкими менструальними кровотечами, дисменореєю, тазовими та головними болем, нудотою, розладами шлунка, частими сечовипусканнями. Мали місце підвищені рівні тромбоцитів, моноцитів, ШОЕ, фібриногену, D-димеру та знижені гемоглобіну, еритроцитів, лімфоцитів, феритину, вітаміну D. Антитіла IgG SARSCov-2 (COVID-19) (коефіцієнт позитивності) виявлено у 100 % жінок в межах 1,84–1,90. Висновки. Особливості клінічного перебігу дифузної форми аденоміозу І – ІV ступеня тяжкості у жінок репродуктивного віку після перенесеного захворювання COVID–19 полягають в активації симптомів основного захворювання, прогресуючої анемізації організму, підвищенні тромботичної активності крові. Представлені ускладнення є обґрунтуванням до визначення персоніфікованої тактики ведення пацієнток після перенесеного захворювання

A Novel Lactic Acid Bacteria Mixture: Macrophage-Targeted Prophylactic Intervention in Colorectal Cancer Management

Colorectal cancer (CRC) is one of the most common forms of cancer. Its onset from chronic inflammation is widely accepted. Moreover, dysbiosis plays an undeniable role, thus the use of probiotics in CRC has been suggested. They exhibit both anti- and pro-inflammatory properties and restore balance in the microbiota. The aim of this study was to investigate the immunomodulatory properties of six lactobacilli with probiotic features in an in vitro model of macrophage-like cells and to test these pooled probiotics for their anti-tumour properties in a chemically induced CRC model using Wistar male rats. Upon co-culture of M1- and M2-like macrophages with lactobacilli, cytokine release (TNF-α, IL-1β, IL-18, IL-23) and phagocytic activity using fluorescent-labelled bacteria were tested. The effects of orally administered probiotics on basic cancer and immune parameters and cytokine concentration (TNF-α, IL-1β, IL-18) in colon tumours were studied. Tested lactobacilli exhibited both pro- and anti-inflammatory properties in in vitro conditions. In vivo study showed that the administration of probiotics was able to decrease multiplicity, volume and total tumour numbers, restore colon length (p &lt; 0.05) and increase IL-18 production (p &lt; 0.05) in tumour tissue. These data indicate both an immunomodulatory effect of probiotics on distinct macrophage subsets and a protective effect against chemically-induced CRC.</jats:p

THE CONTENT OF PROSTANOIDS AND CYCLOOXYGENASES IN COLON TISSUE IN EXPERIMENTAL ULCERATIVE COLITIS

Introduction. The article examines changes in the content of prostaglandins and cyclooxygenases (COX) in colon tissue in ulcerative colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) in a 50% ethanol solution. Based on the obtained results, the authors conclude that changes in the content of the studied parameters, except PGI2, are due to ethanol effect, not DNBS. Both COX isozymes are expressed in normal colon and reduced in ulcerative colitis. The aim. To study the prostanoids (PGE2, PGI2, PGF2α, TBX2 and 8-iso-PGF2α) and COX-1 and -2 contents in colon tissue in experimental ulcerative colitis. Materials and methods. The determination of prostanoids and cyclooxygenases contents in colon tissue by enzyme immunosorbent assay was carried out on three groups of sexually mature laboratory rats of both sexes of the WAG population (1st control group – intrarectal injection of saline; 2nd control group – injection of 50% ethanol; experimental group – injection of DNBS in 50% ethanol). Results. PGE2 and PGI2 contents in colon tissue of experimental group rats were statistically significantly higher compared 1st and 2nd control groups. The content of PGE2 was also increased in 2nd control group versus 1st control one. The increasing PGI2 in 2nd control group versus 1st control was not significant. TBX2 and PGF2α contents in experimental and 2nd control groups were significantly lower compared 1st control. 8-iso-PGF2α (non-enzymatically derived prostanoid) level in experimental group rats was significantly higher compared both controls. 8-iso-PGF2α content in 2nd control group was significantly higher compared 1st one. The content of both COX isoforms in colon tissue in experimental group and 2nd control group rats was significantly lower compared to 1st control group. Conclusions. Both isoforms of COX are expressed in control group colon indicating COX-2 involvement in supporting physiological functions of normal colon tissue. All studied indicators changes, except PGI2, are due to ethanol, not DNBS. Both 50% ethanol and DNBS in 50% ethanol stimulate lipid peroxidation, confirmed by significant increase in 8-iso-PGF2α content. PGE2 and PGF2α contents changes against the background of reduced levels of COX-1 and COX-2 in experimental ulcerative colitis are most likely an adaptive response aimed at maintaining colon homeostasis. PGI2 content changes are due to DNBS, and not to ethanol

Natural Epigenetic Modulators of Vitamin D Receptor

Vitamin D plays an important role in every tissue due to its differentiating properties and the control of calcium homeostasis. The reversion of the epigenetic repression of the vitamin D receptor (VDR) could lead to an increased sensitivity of the cells to the beneficial activity of the hormone and could be exploited in many vitamin D-resistant diseases. In this study we analyzed the effects of three natural epigenetic modulators: sulforaphane, curcumin, and the products of the fermentative activity of probiotics. Sulforaphane and curcumin are inhibitors of the DNA methyltransferases (DNMT) and of the histone deacetylases (HDAC); it has been demonstrated that sulforaphane and curcumin increase VDR expression in intestinal epithelial cells and in a human liver cancer cell line, respectively. The anti-inflammatory properties associated with the probiotic administration in vivo can be linked to the increased activity of intestinal VDR. Butyrate, an inhibitor of HDAC and a known modulator of VDR expression, is the candidate byproduct of fermentation by gut microbiome that could mediate the enhanced expression of VDR triggered by probiotics in vivo. Many other natural compounds wait to be investigated and recognized as epigenetic modulators of VDR, thus opening promising therapeutic avenues for many diseases by natural means