MYOFIBROBLASTS HINDER RECOVERY OF HASHIMOTO THYROIDITIS IN THE ULTRASTRUCTURAL LEVEL.

Background: Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is counteracted by increased collagen production, deposition and scarring. However, only recently a specific subpopulation of modified fibroblasts with contractile properties, namely "myofibroblasts" (MFBs) have been linked to HT. Aim: Our ultrastructural study aims to delineate the presence and contribution of MFBs to the fibrotic milieu of HT. Material and Methods: Tissue biopsies were obtained from 5 HT-diagnosed patients and specimens were examined using a Transmission Electron Microscope (TEM). Results: Histopathological examination indicated extensive microvilli atrophy and atypical vacuolations of the thyroid follicular cells in the HT samples. In addition to interstitial extravasated lymphocytes, capillaries were encircled by MFBs (mean distance from lumen 1.248± 0.43µm) with the characteristic electron-dense α-smooth muscle actin (α-SMA), confirmable in higher magnifications. Myofibroblastic projections were found to have significantly higher representation near the capillary lumen compared to the impaired endothelial lining (P < 0.01). Conclusion: Our TEM findings suggest that the intrusion of endothelia by myofibroblastic projections can be a significant factor towards the malfunction of follicular cells in HT patients and offer a paradigmal understanding of the ultrastructural interactions that may underlie the HT pathology.

Immunohistochemical investigation of metabolic markers fatty acid synthase (FASN) and glucose transporter 1 (GLUT1) in normal endometrium, endometrial hyperplasia, and endometrial malignancy.

BACKGROUND: Cancer cells present higher metabolic needs in comparison to their normal, non-neoplastic counterparts, consuming carbohydrates as a source of energy. Moreover, increased fatty acid biosynthesis is noted in many malignancies. In this regard, we investigated specific metabolic markers, the fatty acid synthase (FASN) which catalyzes fatty acid synthesis and the glucose transporter 1 (GLUT1) which promotes glucose transport through the cellular membrane, in normal endometrium, endometrial hyperplasia, and endometrial malignancy. METHODS: We examined the immunohistochemical expression of GLUT1 and FASN in 43 cases of endometrioid adenocarcinoma, 15 cases of serous endometrial carcinoma, eight cases of clear cell endometrial carcinoma, 11 cases of atypical hyperplasia / endometrial intraepithelial neoplasia, 17 cases of simple hyperplasia, and 20 cases of normal endometrium. RESULTS: We observed a gradual increase in the expression of both markers, progressing from benign clinical conditions to malignancy. The most notable finding concerned the difference of FASN immunoreactivity between atypical hyperplasia and grade 1 endometrioid adenocarcinoma (p =0.01). CONCLUSION: GLUT1 and FASN expression demonstrated a gradual increase when advancing from endometrial hyperplasia to carcinoma. These findings suggest that both GLUT1 and FASN immunohistochemistry might be used as an adjunct in the differentiation between atypical endometrial hyperplasia and endometrial carcinoma in complex cases. HIPPOKRATIA 2017, 21(4): 169-174.

Embolization after percutaneous coronary intervention in acute coronary syndrome. Saphenous vein grafts versus native coronary arteries.

AIMS: The aim of this study was to assess the occurrence of distal embolization and to quantify the amount of embolic material captured during stent implantation in native coronary arteries, as compared with saphenous vein grafts (SVG) in patients at different time periods after an acute coronary syndrome. PATIENTS AND METHODS: In all, 104 patients presenting with unstable or stable angina underwent percutaneous coronary intervention (PCI) in 107 vessels and stent implantation in 112 lesions, 53 % of which were in SVG. RESULTS: Device deployment and retrieval was successful in 111 lesions. Embolic material was detected in 74 % of the protection devices. Early PCI, during a 2-week period after the last ischemic episode, was associated with larger embolic load, especially in the right coronary artery. The length of the lesion was the only preprocedural independent variable that was found to be a significant predictor for the presence of emboli (p = 0.002). The stent diameter and the maximum dilatation pressure were the two procedural variables found to be significant predictors for the presence of emboli (p = 0.025 and p = 0.008, respectively). The irregularity of the lesion and the number of stents deployed were found to have a predictive correlation to the total area of the embolic particles (p = 0.04 and p = 0.005, respectively). CONCLUSION: Distal embolization of atherosclerotic debris is a frequent phenomenon after PCI not only in SVG but also in native vessels. The amount of embolic material seems to be related to the atherosclerotic burden of the vessel and to the early timing of the procedure as related to acute coronary syndrome.

Delayed post-ischaemic administration of xenon reduces brain damage in a rat model of global ischaemia.

OBJECTIVE: Xenon and nitrous oxide have been shown to be neuroprotective in vivo and in vitro, but mainly in models of focal cerebral ischaemia. This study aimed to investigate whether the two gases are able to attenuate cerebral injury after global cerebral ischaemia. METHODS: Adult male Wistar rats underwent bilateral common carotid artery occlusion and were ventilated for 1 hour with 21% O2/78% N2. They were then randomized to three groups which continued to receive atmospheric air, 50% N2O/50% O2 and 50% Xe/50% O2 for an additional period of 45 minutes. The number of ischaemic neurons, the cortical volume loss and the immunochemical and molecular expression of c-fos and MMP-9 were evaluated. RESULTS: Xenon reduced the number of ischaemic neurons in the cortex and CA1 hippocampal region (p < 0.001) and decreased the cortical volume loss (p < 0.01). Immunochemical induction of c-fos in the cortex was significantly suppressed (p < 0.01) after administration of xenon. The molecular analysis revealed significant effects of N2O and xenon administration on c-fos and MMP-9 expression. CONCLUSIONS: The data indicate that N2O and xenon administration is neuroprotective 1 hour after bilateral common carotid artery occlusion. These findings provide valuable evidence on the beneficial role of N2O and xenon in global cerebral injury.

Is copper chelation an effective anti-angiogenic strategy for cancer treatment?

Angiogenesis and the acquisition of an angiogenic phenotype is important for cancer cell proliferation. Copper in an essential trace element that participates in many enzymatic complexes like the cytochrome c, superoxide dismutase and lysyl oxidase and it is involved in processes, like embryogenesis, growth, angiogenesis and carcinogenesis. In particular, its involvement in carcinogenesis was described for the first time in oral submucous fibrosis, where fibroblasts produce large amounts of collagen in the presence of copper. Copper's action in carcinogenesis is two-fold: (1) it participates in reactions with an increased redox potential that result in the production of oxidative products and oxidative stress. Through this mechanism, copper may cause DNA mutations in the nucleus and mitochondria or alterations to membrane phospholipids, (2) it participates in angiogenesis even in the absence of angiogenic molecules, as it was reported for the first time in rabbit cornea models with copolymer pellets charged with PGE1. Copper chelation regimens like penicillamine and tetrathiomolybdate are being described in the literature as having anti-angiogenic, anti-fibrotic and anti-inflammatory actions. Animal models of brain cancer that evaluated the anti-angiogenic properties of copper, have proven evidence of the reduction of tumor's microvascular supply, tumor volume and vascular permeability after plasma copper levels reduction. Interestingly, plasma copper levels reduction was shown to suppress micrometastases generation in mice models of breast cancer. We hypothesize that copper chelation therapy: increases oxidative stress in cancer cells to a level that does not allow survival because of the reduction of anti-oxidative enzymes production. It may also result in inhibition of angiogenesis and of the initiation of the angiogenic switch, because copper normally enhances endothelial cell migration and proliferation, improves binding of growth factors to endothelial cells and enhances the expression of angiogenic molecules. Copper chelation may also reduce extracellular matrix degradation and cancer spread, through reduction of MMP-9 production and probably of other collagenases and may inhibit propagation of micrometastases. However, copper chelation therapy may enhance angiogenesis through reduction of thrombospondin-1, that results into an increase in VEGF-VEGFR2 complexes and a high level of active MMP-9. These hypotheses help in understanding of the anti-angiogenic action of copper chelation therapies and of the complex network of interactions between copper and other molecules involved in angiogenesis. It may also stimulate further research regarding differences in copper metabolism, the effects of anti-copper regimens on organs, the development of resistance, and their possible angiogenic action through thrombospondin expression reduction.

Human pulmonary Dirofilariasis: one more case in Greece suggests that Dirofilaria is a rather common cause of coin lesions in the lungs in endemic areas of Europe.

Herein we describe a case of a 52 year-old male from Greece who presented with a coin lesion in the right lung, which proved to be an infection from Dirofilaria immitis. A careful review of the literature shows that, contrary to the common perception, humans may be frequently infected by Dirofilaria species. For this reason the authors suggest that in every case which presents with a coin lesion in the lung in endemic areas, dirofilariasis should always be considered, and excluded before any other intervention is decided.

Effects of rich-in-fat diets and highly selective COX-2 inhibitors on 7,12-dimethylbenz-(A)-anthracene-induced tumor growth.

The effects of diet, of non-steroidal anti-inflammatory drugs, or of their combination on carcinogenesis continue to be a case for controversy. Diets that are high in fat have been linked to increased risk of various tumors. At the same time there is substantial, but not conclusive, evidence that the risk of breast and colon cancer correlates with total fat intake rather than a specific type of fat. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDs) have been studied extensively because they appear to delay or inhibit the development of malignant and pre-malignant lesions. 7,12-Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce carcinogenesis in a number of rat animal models. The present study attempts to identify the effects on DMBA-induced tumor growth (a) of diets rich in fat and (b) of the highly selective COX-2 inhibitor Celecoxib, which has been claimed to offer substantial protection against carcinogenesis.

Immunohistochemical phenotyping and PCNA detection in gastrointestinal stromal tumors.

The immunohistochemical profile and the expression of proliferating cell nuclear antigen (PCNA) were studied in a series of 44 mesenchymal tumors of the gastrointestinal tract (GIT). On routinely hematoxylin-eosin stained sections 31 cases were classified as leiomyomas or leiomyomatoid tumors, 12 as leiomyosarcomas and 1 as a neurilemmoma. Immunohistochemical stains for smooth muscle antigen (SMA), S-100 protein, glial fibrillary acidic protein (GFAP), vimentin and desmin were performed with the peroxidase-antiperoxidase method on paraffin sections. The streptavidin-biotin method for PCNA immunostaining was applied using the monoclonal antibody PC 10. On the basis of immunohistochemical findings, 32 cases were identified as leiomyomatoid tumors or leiomyosarcomas (SMA positive, S-100 protein negative), 2 cases as nerve sheath tumors (SMA negative, S-100 protein and GFAP positive), whereas 8 cases presented a mixed phenotype (SMA positive and S-100 protein positive). Two cases were negative for both SMA and S-100 protein. All tumors showed positive immunostaining for vimentin and a negative one for desmin. There was a correlation between the histologic grade and proliferating score, displayed by PCNA expression in tumors of smooth muscle origin. The PCNA expression in tumors of mixed phenotype was intermediate to that seen in leiomyosarcomas (high expression) and in leiomyomas (low expression).