Rola infekcji wirusem Epstein-Barr’a w rozwoju autoimmunologicznych chorób tarczycy

Introduction: Autoimmune thyroid diseases, including Graves’ and Hashimoto’s thyroiditis, are the most frequent autoimmune disorders. Viral infection, including Epstein-Barr virus (EBV), is one of the most frequently considered environmental factors involved in autoimmunity. Its role in the development of AITD has not been confirmed so far.Material and methods: Surgical specimens of Graves’ and Hashimoto’s diseases and nodular goitres were included in the study. The expression of EBV latent membrane protein 1 (LMP1) was analysed by immunohistochemistry, with the parallel detection of virus-encoded small nuclear non-polyadenylated RNAs (EBER) by in situ hybridisation.Results: In none of the Graves’ disease specimens but in 34.5% of Hashimoto’s thyroiditis cases the cytoplasmic expression of LMP1 was detected in follicular epithelial cells and in infiltrating lymphocytes. EBER nuclear expression was detected in 80.7% of Hashimoto’s thyroiditis cases and 62.5% of Graves´ disease cases, with positive correlation between LMP1 and EBER positivity in all Hashimoto’s thyroiditis LMP1-positive cases.Conclusions: We assume that high prevalence of EBV infection in cases of Hashimoto’s and Graves’ diseases imply a potential aetiological role of EBV in autoimmune thyroiditis. The initiation of autoimmune thyroiditis could start with EBV latency type III infection of follicular epithelium characterised by LMP1 expression involving the production of inflammatory mediators leading to recruitment of lymphocytes. The EBV positivity of the infiltrating lymphocytes could be only the presentation of a carrier state, but in cases with EBER+/ LMP1+ lymphocytes (transforming latent infection) it could represent a negative prognostic marker pointing to a higher risk of primary thyroid lymphoma development. (Endokrynol Pol 2015; 66 (2): 132–136)Wstęp: Autoimmunologiczne choroby taczycy, w tym zapalenia tarczycy Graves’a i Hashimoto, są najczęstszymi zaburzeniami autoimmunologicznymi. Infekcja wirusowa, w tym wirusem Epstein-Barr’a (EBV), jest jednym z najczęściej rozważanych czynników środowiskowych łączonych z autoimmunologią. Jego rola w rozwoju autoimmunologicznyh chorób taczycy (AITD) nie została do tej pory potwierdzona.Materiały i metody: Zbadano chirurgicznie pobrane preparaty od chorych na chorobę Gravesa, chorobę Hashimoto i wole guzowate. Ekspresja latentnego białka błonowego 1 (LMP1) EBV była zanalizowana metodami immunohistochemicznymi, z równoczesnym wykrywaniem kodowanych wirusem, małych, jądrzastych, niespoliadenylowanych RNA (EBER) poprzez hybrydazcję in situ.Wyniki: W żadnym z przypadków choroby Gravesa nie stwierdzono w komórkach pęcherzykowych i naciekających limfocytach ekspresji LMP1w cytoplazmie, ale wykryto ją w 34,5% przypadkach choroby Hashimoto. Jądrowa ekspresja EBER została wykryta w 80,7% przypadków zapalenia tarczycy Hashimoto i w 62,5% choroby Gravesa. Zauważono również dodatnią korelację pomiędzy LMP1 i występowaniem EBER we wszystkich przypadkach choroby Hashimoto LMP1+.Wnioski: Autorzy uwazają, że powszechne występowanie infekcji EBV w chorobach Hashimoto i Gravesa sugeruje potencjalną rolą etiologiczną EBV w rozwoju autoimmunologicznych zapaleń tarczycy. Zapoczątkowaniem autoimmunologicznych zapaleń tarczycy może być utajona infekcja EBV typu III, charakteryzująca się ekspresją LMP1 w komórkach pęcherzykowych i związana z produkcją mediatorów zapalnych prowadzącą do migracji limfocytów. Obecność EBV w naciekach limfocytarnych może być jedynie charakterystyczna dla nosiciela wirusa ale w przypadku obecności limfocytów EBER+/LMP1+ (przekształcajcych infekcję utajoną) może być negatywnym markerem prognostycznym wskazując podwyższone ryzyko rozwoju pierwotnego chłoniaka tarczycy. (Endokrynol Pol 2015; 66 (2): 132–136

Effect of Bioactive Compound of Aronia melanocarpa

Aronia melanocarpa has attracted scientific interest due to its dense contents of different polyphenols. We aimed to analyse effects of Aronia melanocarpa (AME) extract on blood pressure (BP), lipid peroxidation, cytokine level, total NOS activity in the left ventricle (LV), and aorta of L-NAME-induced hypertensive rats. 12-week-old male WKY rats were assigned to the control group and groups treated with AME extract (57.90 mg/kg/day), L-NAME (40 mg/kg/day), or combination of L-NAME (40 mg/kg/day) and AME (57.90 mg/kg/day) in tap water for 3 weeks. NOS activity, eNOS protein expression, and conjugated diene (CD) concentration were determined in the LV and aorta. After 3 weeks of L-NAME treatment, BP was increased by 28% and concomitant treatment with AME reduced it by 21%. NOS activity of the LV and aorta in the L-NAME group was decreased by about 40%, while AME increased it almost on the control level. AME-induced eNOS upregulation may contribute to increase NOS activity. Moreover, AME decreased CD concentration in the LV and aorta and TNF-α and IL-6 production in the plasma were increased by L-NAME treatment. In conclusion, our results showed that active substances of Aronia melanocarpa may have a positive effect on blood pressure, NOS activity, and proinflammatory processes in L-NAME-induced hypertension

Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension

<p>Abstract</p> <p>Background</p> <p>Increase of blood pressure is accompanied by functional and morphological changes in the vascular wall. The presented study explored the effects of curcuma and black pepper compounds on increased blood pressure and remodeling of aorta in the rat model of experimental NO-deficient hypertension.</p> <p>Methods</p> <p>Wistar rats were administered for 6 weeks clear water or L-NAME (40 mg/kg/day) dissolved in water, piperine (20 mg/kg/day), curcumin (100 mg/kg/day) or their combination in corn oil by oral gavage. The systolic blood pressure was measured weekly. Histological slices of thoracic aorta were stained with hematoxylin and eosin, Mallory's phosphotungstic acid hematoxylin (PTAH), orcein, picrosirius red and van Gieson staining and with antibodies against smooth muscle cells actin. Microscopic pictures were digitally processed and morphometrically evaluated.</p> <p>Results</p> <p>The increase of blood pressure caused by L-NAME was partially prevented by piperine and curcumin, but the effect of their combination was less significant. Animals with hypertension had increased wall thickness and cross-sectional area of the aorta, accompanied by relative increase of PTAH positive myofibrils and decrease of elastin, collagen and actin content. Piperine was able to decrease the content of myofibrils and slightly increase actin, while curcumin also prevented elastin decrease. The combination of spices had similar effects on aortic morphology as curcumin itself.</p> <p>Conclusions</p> <p>Administration of piperine or curcumin, less their combination, is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. The spices modify the remodeling of the wall of the aorta induced by hypertension. Our results show that independent administration of curcumin is more effective in preventing negative changes in blood vessel morphology accompanying hypertensive disease.</p

Збройні сили Гетьманщини та Запорожжя в боротьбі з Османською імперією в 1695-96 рр. за даними неопублікованих листів Івана Мазепи

Російський історик М.Богословський ще в 20-х рр. XX ст. слушно зауважив, що в історичній літературі зверталося порівняно мало уваги на завоювання дніпровських містечок в кінці XVII ст., оскільки вся увага була прикута до Азова, де діяв сам Петро І. Але зроблене тут мало не менше значення ніж взяття Азова, бо в результаті Росія наближалася до Чорного моря як зі східного, так і з західного боку. Під контролем з обох боків опинявся й Крим [1]. В 1695-1696 рр. збройні сили Російської держави та Війська Запорозького здійснили два походи на Азов та один на пониззя Дніпра, маючи на меті завоювання виходів до Азовського та Чорного морів. Похід на Азов у 1695 р., як відомо, був невдалим. Натомість похід російських військ на чолі з боярином Борисом Шереметєвим та українських сил, очолюваних гетьманом Іваном Мазепою, а також запорожців на пониззя Дніпра наприкінці липня – на початку серпня увінчався взяттям важливого плацдарму, де знаходилося чотири турецькі фортеці – Казикермен, Мустріткермен, Мубеуреккермен і Ісламкермен. В Мустріткермені (Таванську), котрий знаходився на острові Тавань, укріплення постраждали найменше. Тому тут було здійснено ремонтні роботи й залишено залогу. Досліджуючи неопубліковану епістолярну спадщину Мазепи в зібраннях Російського державного архіву давніх актів, ми виявили ряд листів, які стосуються участі Лівобережної України та Запорозької Січі у воєнних діях проти Османської імперії у згадані роки. Так, віднайдено чотири листи, котрі були написані напередодні походу 1695 р. Три з них адресувалися царям – від 26 березня, 1 квітня та 14 квітня, а один – боярину Леву Наришкіну від 26 березня. Отже, розглянемо їх зміст, з точки зору задекларованої теми. З першого з пропонованих документів дізнаємося, що перед походом гетьманський уряд вживав заходів для збору інформації щодо противника. Так, у листі до царів від 26 березня 1695 р. Мазепа повідомляв, що товариство Полтавського полку – понад сотня козаків на чолі з царичанським сотником і кількома польовими ватажками ходили на воєнні промисли з його відома. Поблизу Перекопа на шляху до Казикермена козаки захопили в полон 22 татарина і привели до Батурина. Мазепа відправляв “язиків” до Москви разом з козаками. Він висловлював сподівання, що полонених буде більше, бо під помешкання противника було послано й інші ватаги. Одну очолював колишній кошовий отаман Федько, другу – колишній кошовий Іван Гусак, третю – полковий осавул Іван Рубан, четверту – кінний сотник Гнат. У перших трьох ватагах нараховувалося по кілька сотень осіб та й четверта була “в немалому зібранні”. Крім того до Мазепи писав Семен Палій, повідомляючи, що його люди пішли на Очаківський шлях, який спрямовувався на Білгород, 6 тижнів тому. У зв’язку з цим гетьман хотів отримати царський указ про те, чи посилат

Pericardial malignant infiltration as the cause of sudden death of a patient with metastatic urothelial carcinoma treated with atezolizumab

Abstract Background Muscle-infiltrating urothelial carcinoma of the bladder is the most common genitourinary cancer. Immunotherapeutic agents targeting protein-1 programmed death or protein-1 programmed death ligand are currently considered the standard treatment in patients with either inoperable locally advanced or metastatic urothelial carcinoma (MUC) after platinum-based chemotherapy failure. Case presentation Here we report the case of a Caucasian male patient with metastatic urothelial carcinoma treated with second-line atezolizumab within a trial who achieved complete response by computed tomography (CT), but suddenly died due to cardiac tamponade resulting from malignant pericardial infiltration. Histopathology confirmed this as the only site of disease progression. Conclusions Cardiovascular toxicity of atezolizumab was considered within differential diagnoses, however histopathological examination revealed progression of malignancy in the pericardium as the cause of the sudden death. This is the first published case report of a patient treated with second-line atezolizumab in whom the rare disease progression of pericardial infiltration was confirmed. Despite its rarity, the clinicians should always consider the possibility of pericardial metastases

Long COVID Complicated by Fatal Cytomegalovirus and Aspergillus Infection of the Lungs: An Autopsy Case Report

After the acute phase of COVID-19, some patients develop long COVID. This term is used for a variety of conditions with a complex, yet not fully elucidated etiology, likely including the prolonged persistence of the virus in the organism and progression to lung fibrosis. We present a unique autopsy case of a patient with severe COVID-19 with prolonged viral persistence who developed interstitial lung fibrosis complicated by a fatal combination of cytomegalovirus and Aspergillus infection. SARS-CoV-2 virus was detected at autopsy in the lungs more than two months after the acute infection, although tests from the nasopharynx were negative. Immune dysregulation after COVID-19 and the administration of corticoid therapy created favorable conditions for the cytomegalovirus and Aspergillus infection that were uncovered at autopsy. These pathogens may represent a risk for opportunistic infections, complicating not only the acute coronavirus infection but also long COVID, as was documented in the presented case

Intrauterine Fetal Demise After Uncomplicated COVID-19: What Can We Learn from the Case?

Background: SARS-CoV-2 infection in pregnant women can lead to placental damage and transplacental infection transfer, and intrauterine fetal demise is an unpredictable event. Case study: A 32-year-old patient in her 38th week of pregnancy reported loss of fetal movements. She overcame mild COVID-19 with positive PCR test 22 days before. A histology of the placenta showed deposition of intervillous fibrinoid, lympho-histiocytic infiltration, scant neutrophils, clumping of villi, and extant infarctions. Immunohistochemistry identified focal SARS-CoV-2 nucleocapsid and spike protein in the syncytiotrophoblast and isolated in situ hybridization of the virus’ RNA. Low ACE2 and TMPRSS2 contrasted with strong basigin/CD147 and PDL-1 positivity in the trophoblast. An autopsy of the fetus showed no morphological abnormalities except for lung interstitial infiltrate, with prevalent CD8-positive T-lymphocytes and B-lymphocytes. Immunohistochemistry and in situ hybridization proved the presence of countless dispersed SARS-CoV-2-infected epithelial and endothelial cells in the lung tissue. The potential virus-receptor protein ACE2, TMPRSS2, and CD147 expression was too low to be detected. Conclusion: Over three weeks’ persistence of trophoblast viral infection lead to extensive intervillous fibrinoid depositions and placental infarctions. High CD147 expression might serve as the dominant receptor for the virus, and PDL-1 could limit maternal immunity in placental tissue virus clearance. The presented case indicates that the SARS-CoV-2 infection-induced changes in the placenta lead to ischemia and consecutive demise of the fetus. The infection of the fetus was without significant impact on its death. This rare complication of pregnancy can appear independently to the severity of COVID-19’s clinical course in the pregnant mother

The Potential of Liquid Biopsy in Detection of Endometrial Cancer Biomarkers: A Pilot Study

Endometrial cancer belongs to the most common gynecologic cancer types globally, with increasing incidence. There are numerous ways of classifying different cases. The most recent decade has brought advances in molecular classification, which show more accurate prognostic factors and the possibility of personalised adjuvant treatment. In addition, diagnostic approaches lag behind these advances, with methods causing patients discomfort while lacking the reproducibility of tissue sampling for biopsy. Minimally invasive liquid biopsies could therefore represent an alternative screening and diagnostic approach in patients with endometrial cancer. The method could potentially detect molecular changes in this cancer type and identify patients at early stages. In this pilot study, we tested such a detection method based on circulating tumour DNA isolated from the peripheral blood plasma of 21 Slovak endometrial cancer patients. We successfully detected oncomutations in the circulating DNA of every single patient, although the prognostic value of the detected mutations failed to offer certainty. Furthermore, we detected changes associated with clonal hematopoiesis, including DNMT3A mutations, which were present in the majority of circulating tumour DNA samples

Deposits of iron oxides in the human globus pallidus

Samples taken from the human brain (Globus Pallidus) have been investigated by physical techniques such as light microscopy, scanning electron microscopy, transmission electron microscopy, Mössbauer spectroscopy and SQUID magnetometry. SEM-EDX/TEM investigation reveals multielemental composition of hematite and magnetite nanocrystals with sizes ranging from 40 nm to 100 nm and hematite microcrystals from 3 μm to 7 μm. Room temperature Mössbauer spectra show quadrupole doublets assigning to hematite and ferrihydrite. SQUID measurements of temperature dependence of the mass magnetic susceptibility between T = 2 – 300 K at DC field B0 = 0.1 T, the field dependence of the mass magnetization taken at the fixed temperature T0 = 2.0 and 4.6 K and the zero-field cooled and field cooled magnetization experiments (ZFCM/FCM) confirm a presence of ferrimagnetic phases such as maghemite and/or magnetite with hysteresis loops surviving until the room temperature. Differences between these measurements from the point of view of iron oxides detected can indicate important processes in human brain and interactions between ferritin as a physiological source of iron and surrounding environment