Immunohistochemical evaluation of potential molecular targets of desmoid-type fibromatosis.

Desmoid-type fibromatosis is locally aggressive tumor rare in general population, although commonly present in patients with familial adenomatous polyposis, significantly contributing to the morbidity and mortality of patients. To optimize and individualize the management of patients it is necessary to better understand the biology of these tumors. Immunohistochemical analysis of ß-catenin, VEGF, hormone receptors ERß, ERα and PR, COX-2, APC protein, EGFR, c-kit (CD117), bcl-2 and HER2 expression, potential therapeutic targets, was carried out on 15 archival biopsy samples together with APC gene mutational screening. ß-catenin expression was found in all samples, with over 73% showing high range positivity, however with no prognostic significance. Non-specific cytoplasmic localization of ß-catenin was observed FAP-associated cases lacking CTNNB1 mutations. Hormone receptor status demonstrated expression of ERß in 93% of lesions, without detectable ERα or PR. Distinct COX-2 expression of variable intensity was present in all but one desmoid-type fibromatosis case. All lesions demonstrated intense VEGF positivity. Immunoreactivity for the APC protein was found only in 4 cases associated with FAP. No EGFR, HER2, bcl-2 or c-kit expression was detected in any sample. Expression of ß-catenin, VEGF, ERß, COX-2 in high number of cases suggests a potential as future therapeutic targets in desmoid-type fibromatosis.

Intermediate trophoblast--A distinctive, unique and often unrecognized population of trophoblastic cells.

The trophoblast forms an outer layer of the blastocyst in the developing placenta and fetal membrane chorion. It is composed of different types of cells. Two main cell types are cytotrophoblasts and syncytiotrophoblasts. The third type of trophoblastic cells, often "forgotten" in most of histological and embryological textbooks, is morphologically and functionally between the first and second one, therefore, it is called the intermediate trophoblast. There is no mention of it in the internationally accepted Terminologia Embryologica. This term is not universally used by pathologists as some of them prefer the name extravillous trophoblast. This review provides an overview of morphology, localization, function and immunohistochemistry of different types of intermediate trophoblast cells. An indisputable reason for categorizing these cells as a distinct group is the fact that they are a source of various forms of gestational trophoblastic disease.

The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases.

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.

Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthritis.

The aim of this study was to evaluate the morphological changes in the spleen, the thymus and the knee joints of rats with experimental adjuvant arthritis induced by Mycobacterium butyricum in the incomplete Freund's adjuvant and the effect of treatment with methotrexate (MTX). Particular attention was aimed on the redistribution of granulocytes in the tissues during the inflammatory process. Clinical parameters, e.g., joint edema, body weight and of gamma glutamyl transferase (GGT) activity as an inflammatory marker, have also been determined. Induction of adjuvant arthritis caused a significant decrease in granulocyte number in the spleen and vice versa a significant increase in the knee joints, but without significant changes in the thymus. Treatment with methotrexate reversed this phenomenon by increasing the granulocyte number in the spleen and decreasing it in knee joints. MTX decreased the joint edema as well as the activity of GGT in the spleen, modified the size of the white pulp of the spleen and increased the cortex/medulla ratio in the thymus. The observed changes support the anti-inflammatory and immunomodulatory properties of MTX supporting its use as the first-line medication in patients with rheumatoid arthritis.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.