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

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

Expression of Constitutive Nitric Oxide Synthase Isoforms in Varicose Vein Wall; Preliminary Results

There are conflicting findings in literature about the structural changes of the primary varicose veins. NO (a potent vasodilatator) is synthesized by nitric oxide synthase (NOS). From 3 known NOS isoforms the two are constitutional: eNOS (endothelial NOS) and nNOS (neuronal NOS). 10 varicose and 10 control vein samples were processed by standard light microscopy and immuno-histochemica techniques using rabbit polyclonal antibodies against eNOS and nNOS. Antibodies expression was evaluated semiquantitatively and proved morphometrically by 2D-image analysis. total area of NOS isoforms expressions was determined by color analysis and color digital subtraction. The results showed discontinuous and significantly lower expression of both NOS isoforms the in the tunica media of varicose veins compared with the control group. For the statistical analysis the unpaired t-test was used. Our results suppose lower NO levels in varicose vein wall, deducing that varicose dilatation is due to other mechanism, and they contradict the results of previously published similar works

Effectiveness of sponsorship in handicapped sport in the Czech Republic

Diplomová práce se zabývá sponzoringem sportu handicapovaných v České republice se zaměřením na to, jaký vliv mají nezávislé proměnné (postoj ke sponzorovi, goodwill, zapojení fanoušků) na proměnnou závislou (nákupní záměry). V literární rešerší byl vymezen pojem sponzoring a spotřebitelské chování ve sportu, které dále rozvijí model psychologického kontinua. Výzkum je kvantitativní a tvoří jej dotazníkové šetření. Pro zpracování dotazníkového šetření byly aplikovány statistické metody pomocí softwaru GRETL. Výsledky naznačují, že proměnné nezávislé proměnnou závislou ovlivňují.The thesis deals with sponsorship of handicapped sport in the Czech Republic, focusing on the influence of independent variables (attitude to sponsor, goodwill, involvement of fans) on the dependent variable (purchase intentions). The literary research defined the concept of sponsorship and consumer behaviour in sport, which will further develop the model of the psychological continuum. The research is quantitative and consists of a questionnaire survey. Statistical methods were used to process the questionnaire investigation using GRETL software. The results suggest that independent variables affect the dependent variable

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

Prognostic Value of Apoptosis-Inducing Factor (AIF) in Germ Cell Tumors

Apoptosis is a strictly regulated process essential for preservation of tissue homeostasis. This study aimed to evaluate expression of apoptosis inducing factor (AIF) in testicular germ cell tumors (GCTs) and to correlate expression patterns with clinicopathological variables. Formalin-fixed and paraffin-embedded specimens of non-neoplastic testicular tissue and GCTs obtained from 216 patients were included in the study. AIF expression was detected by immunohistochemistry, scored by the multiplicative quickscore method (QS). Normal testicular tissue exhibits higher cytoplasmic granular expression of AIF compared to GCTs (mean QS = 12.77 vs. 4.80, p p = 0.048). We observed significantly lower AIF expression in GCTs compared to normal testicular tissue, which is an uncommon finding in malignant tumors. AIF downregulation might represent one of the mechanisms of inhibition of apoptosis and promotion of cell survival in GCTs

Evaluation and limitations of different approaches among COVID-19 fatal cases using whole-exome sequencing data

Abstract Background COVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19. Results We selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations. Conclusions Although our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing