Vasa vasorum lumen narrowing in brain vascular hyalinosis in systemic hypertension patients who died of ischemic stroke

Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott–Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients

Морфологічні особливості репаративного процесу в зоні трофічних венозних виразок нижніх кінцівок за умов застосування аутоплазми, збагаченої тромбоцитами

Мета. Дослідити стан регенерації тканин у зоні трофічних виразок венозного ґенезу. Матеріали і методи. Протягом 2017 р. на базі хірургічного відділення Сумського обласного клінічного госпіталю ветеранів війни проведено лікування 57 хворих з трофічними виразками нижніх кінцівок шляхом застосування аутоплазми, збагаченої тромбоцитами (АПЗТ). Результати. На 20-ту добу від початку лікування у хворих основної групи площа виразкового дефекту зменшувалась на 45,8% у порівнянні з вихідними даними, у хворих контрольної групи - лише на 31,4%, що в 1,4 разу менше (p < 0,05). Висновки. Покращення регенерації тканин у зоні виразки за рахунок епідермізації скорочує строки її епітелізації у разі застосування АПЗТ у 2,3 разу

The power of comparative and developmental studies for mouse models of Down syndrome

Since the genetic basis for Down syndrome (DS) was described, understanding the causative relationship between genes at dosage imbalance and phenotypes associated with DS has been a principal goal of researchers studying trisomy 21 (Ts21). Though inferences to the gene-phenotype relationship in humans have been made, evidence linking a specific gene or region to a particular congenital phenotype has been limited. To further understand the genetic basis for DS phenotypes, mouse models with three copies of human chromosome 21 (Hsa21) orthologs have been developed. Mouse models offer access to every tissue at each stage of development, opportunity to manipulate genetic content, and ability to precisely quantify phenotypes. Numerous approaches to recreate trisomic composition and analyze phenotypes similar to DS have resulted in diverse trisomic mouse models. A murine intraspecies comparative analysis of different genetic models of Ts21 and specific DS phenotypes reveals the complexity of trisomy and important considerations to understand the etiology of and strategies for amelioration or prevention of trisomic phenotypes. By analyzing individual phenotypes in different mouse models throughout development, such as neurologic, craniofacial, and cardiovascular abnormalities, greater insight into the gene-phenotype relationship has been demonstrated. In this review we discuss how phenotype-based comparisons between DS mouse models have been useful in analyzing the relationship of trisomy and DS phenotypes

The Problem of Students' Adaptation to the Bologna System

У статті запропоновано деякі результати вивчення процесу адаптації студентів ВНЗ до змін у системі вищої освіти у зв'язку з її реформуванням на основі Болонської декларації.Here are some research results of student’s adaptation for changes in the higher educational system connected with its restructuring based on Bologna declaration

Pulmonary artery embolism by a metal fragment after a booby trap explosion in a combat patient injured in the armed conflict in East Ukraine: a case report and review of the literature

Background: Pulmonary artery embolization due to projectile embolus is a rare complication in combat patients. Such embolization is rare for combat patients in the ongoing armed conflict, in East Ukraine since 2014. Case presentation: We report a clinical case of a 34-year-old Caucasian combat patient who was injured after an explosion of a booby trap hand grenade. This soldier was diagnosed with severe abdominal and skeletal trauma: damage of the duodenum and transverse colon, internal bleeding due to inferior vena cava damage and fractures of both lower extremities. The patient was treated at a highly specialized surgical center within the “golden hour” time. Whole-body computed tomography scan was performed as a routine screening method for hemodynamically stable patients, at which we identified a projectile embolus due to the explosion of a booby trap hand grenade in the right midlobar pulmonary artery. Our patient had no clinical manifestation of pulmonary artery embolism. At follow-up, our patient was diagnosed with the following complications: multiple necrosis and perforations of the transverse colon leading to a fecal peritonitis; duodenum suture line leakage caused the formation of a duodenal fistula; postoperative wound infection. These complications required multiple secondary operations, and in accordance to the principles of damage-control tactics, the extraction of projectile-embolus was postponed. Open surgery retrieval of the metal fragment was successfully performed on the 80th day after injury. Our patient was discharged from the hospital on day 168th after injury. Conclusions: Literature analysis shows a significant difference of clinical management for patient with projectile embolism in hybrid war settings as compared to previously described cases of combat and civil gunshot injuries. Damage control tactics and the concept of the “golden hour” are highly effective for those injured in a hybrid war. A whole-body computed tomography scan is an effective screening method for asymptomatic patients with projectile-embolism of the great vessels. The investigation of a greater cohort of combat patients with severe injuries and projectile-embolism should be performed in order to develop a better guideline for these patients and to save more lives

Neutron scattering investigations of the lipid bilayer structure pressure dependence

Lipid bilayer structure investigation results obtained with small angle neutron scattering method at the Joint Institute for Nuclear Research IBR-2M nuclear reactor (Dubna, Russia) are presented. Experiment has been per-formed with small angle neutron scattering spectrometer YuMO, upgraded with the apparatus for performing P-V-T measurements on the substance under investigation. D2O-1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liquid system, presenting the model of natural live membrane, has been taken as the sample for investiga-tions. The lipid bilayer spatial period was measured in experiment along with isothermal compressibility simulta-neously at different pressures. It has been shown, that the bilayer structural transition from ripple (wavelike gel-phase) phase to liquid-crystal phase is accompanied with anomalous rise of isothermal compressibility, indicat-ing occurrence of the phase transition

Грип A (H1N1) та COVID-19: особливості ураження надниркових залоз

Stressors are one of the causes of adrenal damage in influenza A (H1N1) and COVID-19. When they act, the same type of morphofunctional changes develop in the cortical layer of the adrenal glands. To a greater extent such processes are expressed in adrenocorticocytes of a reticular zone. This does not negate the existence of other mechanisms of adrenal damage by viruses, in particular the mechanism of mimicry of viral peptides to human adrenocorticotropic hormone (ACTH), as a result of which, after the production of antibodies, the latter affect both the pathogen and ACTH, causing hypocorticism. This paper reviews the histological and immuno­histochemical study of the influenza A (H1N1) (3 clinical cases) and COVID-19 (1 clinical case) influence on adrenal glands. The study showed that both influenza A (Н1N1) and COVID-19 cause adrenal damage. Histo­logical changes in these diseases are characterized by edema and partial destruction of endocrine cells in both the medulla and adrenal cortex. However, COVID-19 caused more significant damage to the medulla with reducing of Chromogranin A substrates levels of endocrine cells. In COVID-19 case signs of ischemia in the medulla and adrenal cortex were found, although in influenza A (H1N1) cases the plethora and vasodilatation of microcirculatory vessels were obser­ved. Hypoxic damage in the COVID-19 clinical case was accompanied by accumulation in the cytoplasm of endocrine cells of lipofuscin granules — a marker of activation of free radical oxidation of lipids.Одной из причин повреждения надпочечников при гриппе А (H1N1) и COVID-19 являются стрессогенные факторы. При их воздействии на организм в корковом слое надпочечников развиваются однотипные морфофункциональные изменения. В большей степени такие процессы выражены в адренокортикоцитах сетчатой зоны. Это не отрицает существования других механизмов повреждения вирусами надпочечников, в частности механизма возникновения явления мимикрии вирусных пептидов к человеческому АКТГ, в результате чего, после выработки антител, последние влияют как на возбудитель, так и на АКТГ, вызывая развитие гипокортицизма. Проведено сравнительное аутопсийное гистологическое и иммуногистохимическое исследование надпочечников при гриппе типа A (H1N1) (3 клинических случая) и коронавирусной болезни 2019 (COVID-19) (1 клинический случай). Полученные результаты свидетельствуют о том, что как при гриппе A (H1N1), так и при COVID-19, наблюдается повреждение надпочечников. Гистологи­чес­кие изменения при этих заболеваниях характеризуются отеком и частичной деструкцией эндокринных клеток как коркового, так и мозгового слоя. Однако при COVID-19 наблюдается более значительное повреждение мозгового слоя с потерей эндо­крин­ными клетками субстратов Chromogranin A. В случае COVID-19 в корковом и мозговом слоях надпочечников имеет место малокровие сосудов микроциркуляторного русла со спадением их просвета в отличие от случаев гриппа A (H1N1), при которых отмече­­ны признаки полнокровия и расширения сосудов. Гипоксическое повреждение при COVID-19 сопровождается аккумуляцией в цитоплазме эндокрин­ных клеток гранул липофусцина — маркера активации свободнорадикального окисления липидов.Однією з причин пошкодження надниркових залоз при грипі А (H1N1) і COVID-19 є стресогенні чинники. При їх дії на організм у кірковому шарі надниркових залоз розвиваються однотипні морфофункціональні зміни. Більшою мірою такі процеси виражені в адренокортикоцитах сітчастої зони. Це не заперечує наявності інших механізмів пошкодження вірусами надниркових залоз, зокрема механізму виникнення явища мімікрії вірусних пептидів до людського АКТГ, у результаті чого, після вироблення антитіл, останні впливають як на збудник, так і на АКТГ, спричиняючи розвиток гіпокортицизму.Проведено порівняльне автопсійне гістологічне та імуногістохімічне дослідження надниркових залоз при грипі типу A (H1N1) (3 клінічні випадки) і коронавірусній хворобі 2019 (COVID-19) (1 клінічний випадок). Отримані результати свідчать про те, що як при грипі A H1N1, так і при COVID-19, спостерігається пошкодження надниркових залоз. Гістологічні зміни при цих захворюваннях характеризуються набряком та частковою деструкцією ендокринних клітин як кіркового, так і мозкового шару. Однак при COVID-19 спостерігається більш значне пошкодження мозкового шару з втратою ендокринними клітинами субстрату Хромограніну A. У разі COVID-19 у кірковому та мозковому шарах надниркових залоз має місце малокрів’я судин мікроциркуляторного русла зі спадінням їх просвіту на відміну від випадків грипу A (H1N1), при яких відзначено ознаки повнокрів’я та розширення судин. Гіпоксичне пошкодження при COVID-19 супроводжується акумуляцією в цитоплазмі ендокринних клітин гранул ліпофусцину — маркера активації вільнорадикального окиснення ліпідів

Structure of monomeric full-length ARC sheds light on molecular flexibility, protein interactions, and functional modalities

he activity‐regulated cytoskeleton‐associated protein (ARC) is critical for long‐term synaptic plasticity and memory formation. Acting as a protein interaction hub, ARC regulates diverse signalling events in postsynaptic neurons. A protein interaction site is present in the ARC C‐terminal domain (CTD), a bilobar structure homologous to the retroviral Gag capsid domain. We hypothesized that detailed knowledge of the three‐dimensional molecular structure of monomeric full‐length ARC is crucial to understand its function; therefore, we set out to determine the structure of ARC to understand its various functional modalities. We purified recombinant ARC and analyzed its structure using small‐angle X‐ray scattering and synchrotron radiation circular dichroism spectroscopy. Monomeric full‐length ARC has a compact, closed structure, in which the oppositely charged N‐terminal domain (NTD) and CTD are juxtaposed, and the flexible linker between them is not extended. The modeled structure of ARC is supported by intramolecular live‐cell Förster resonance energy transfer imaging in rat hippocampal slices. Peptides from several postsynaptic proteins, including stargazin, bind to the N‐lobe, but not to the C‐lobe, of the bilobar CTD. This interaction does not induce large‐scale conformational changes in the CTD or flanking unfolded regions. The ARC NTD contains long helices, predicted to form an anti‐parallel coiled coil; binding of ARC to phospholipid membranes requires the NTD. Our data support a role for the ARC NTD in oligomerization as well as lipid membrane binding. The findings have important implications for the structural organization of ARC with respect to distinct functions, such as postsynaptic signal transduction and virus‐like capsid formation