THE INFLUENCE OF THERMAL BRIDGES ON REFRACTORY LININGS

In this study we analyze the influence of thermal bridges caused by the presence of anchoring systems. The engineering, especially heat transfer calculation, allow the preventive definition of the most suitable insulating linings. Thanks to the thermography, it is possible to determine which are the parameters that actually influence the heat transfer process, thus to work with not only theoretical values but also actual ones. Corrective actions together with general considerations are illustrated in this study, supported by drawings, pictures and thermo graphics scans

Macrophages : central regulators of iron balance

Macrophages are important to immune function and also actively participate in iron homeostasis. The involvement of splenic and liver macrophages in the processing of effete erythrocytes and the subsequent return of iron to the circulation is well established, and the molecular details of iron recycling have been characterized recently. Another important aspect regarding iron handling by macrophages is their capacity to act as immune cells, which involves the inflammatory response, as well as other pathological conditions in which macrophages are central. This review discusses the latest advances in macrophage iron trafficking and the pathophysiological consequences of altered iron homeostasis in these cells

Iron-induced damage in cardiomyopathy: oxidative-dependent and independent mechanisms

The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies

Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma : An Overview of Current Perspectives

Cholangiocarcinoma (CCA) is a deadly tumor without an effective therapy. Unique metabolic and bioenergetics features are important hallmarks of tumor cells. Metabolic plasticity allows cancer cells to survive in poor nutrient environments and maximize cell growth by sustaining survival, proliferation, and metastasis. In recent years, an increasing number of studies have shown that specific signaling networks contribute to malignant tumor onset by reprogramming metabolic traits. Several evidences demonstrate that numerous metabolic mediators represent key-players of CCA progression by regulating many signaling pathways. Besides the well-known Warburg effect, several other different pathways involving carbohydrates, proteins, lipids, and nucleic acids metabolism are altered in CCA. The goal of this review is to highlight the main metabolic processes involved in the cholangio-carcinogeneis that might be considered as potential novel druggable candidates for this disease

Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker

Un caso di linfoma cutaneo T gamma/delta

Secondo la classificazione della WHO/EORTC del 2008, fra i linfomi cutanei, una variante molto rara \ue8 rappresentata dal linfoma T cutaneo gamma/delta. Questa entit\ue0 rappresenta circa l'1% dei linfomi T cutanei e si manifesta clinicamente in modo analogo ad altre forme linfoproliferative cutanee. La diagnosi \ue8 istologica, immunoistochimica e molecolare; l'infiltrato neoplastico \ue8 rappresentato da piccole-medie e grandi cellule ed elementi blastici distribuiti secondo 3 diversi pattern: epidermotropo, dermico e sottocutaneo. Le indagini di biologia molecolare risultano caratteristicamente negative per il TCR-beta e evidenziano un riarrangiamento clonale per il TCR-delta1 e TCR-gamma. Descriviamo il caso di una donna di 70 anni in buone condizioni di salute, che presentava da 2 anni lesioni sottocutanee a tipo lupus panniculite ad evoluzione necrotico-ulcerativa in prevalenza localizzate agli arti. La paziente era stata inizialmente sottoposta a terapia con steroidi per via orale, ma la patologia era lentamente progredita. Veniva pertanto eseguita una biopsia cutanea per esame istologico, indagini di immunoistochimica e biologia molecolare. Le indagini eseguite evidenziavano la presenza di un infiltrato linfocitario superficiale e profondo esteso al tessuto adiposo con cellule pleomorfe di piccola e media taglia CD2+, CD3+, CD56+, TCR-delta-1+, Mib-1++, TIA-1++. La paziente \ue8 stata sottoposta a cicli di polichemioterapia (CHOP) con parziale risposta clinica. Nonostante la terapia, il quadro clinico \ue8 andato incontro a progressione con coinvolgimento viscerale in 6 mesi ed exitus per complicazioni cardiocircolatorie e polmonari dopo circa 2 mesi. Questo caso appare peculiare per il suo andamento clinico; il linfoma gamma/delta si caratterizza, infatti, per una iniziale lenta evoluzione ed un successivo rapido coinvolgimento sistemico con importante sintomatologia generale. Il trattamento polichemioterapico non sembra influenzare la prognosi che \ue8 generalmente sfavorevole

Due casi di linfoma cutaneo anaplastico a grandi cellule (C-ALC) CD30+ CD8+ aggressivi

Descriviamo 2 casi inusuali. Il primo caso riguarda una donna di 79 anni, affetta da morbo di Alzheimer, che presentava da un anno lesioni agli arti superiori, insorte inizialmente come chiazze eritematose e diventate nodulari con componente ulcerativa in circa 40 giorni. L\u2019esame istologico ha mostrato densa infiltrazione perivascolare di piccoli linfociti ed elementi linfoidi di medie dimensioni e di aspetto blastico frammisti a polvere cromatinica ed elementi plasmocitoidi. All\u2019immunoistochimica l\u2019infiltrato era CD3+, CD30+, CD8+, Granzyme B+, CD56-, ALK1-, EMA-. Alla biologia molecolare era presente un riarrangiamento policlonale del TCR-gamma. Si \ue8 verificato un rapido coinvolgimento viscerale con interessamento gastrico e linfonodale toracico. La prognosi \ue8 stata infausta nonostante il trattamento polichemioterapico con CVP. Il secondo caso riguarda un uomo di 58 anni, diabetico e cardiopatico. Due anni prima aveva presentato una lesione nodulare al polso sinistro, biopsiata c/o altra sede con diagnosi di LNH a grandi cellule anaplastico primitivo cutaneo. Per la comparsa di analoga lesione alla gamba dx era stato sottoposto a stadiazione con riscontro di linfoadenopatia toracica multipla, per cui era stata intrapresa polichemioterapia con CHOP ed in seguito con VNCOP-B, con buoni risultati clinici. Giunto alla nostra osservazione due mesi fa si \ue8 eseguita biopsia cutanea sulle lesioni nodulari della gamba dx con reperto di infiltrato dermico non epidermotropo di elementi linfocitari medio-grandi, marcatamente pleomorfi con nucleo ipercromatico. All\u2019immunoistochimica le cellule risultavano CD3+, CD8+, CD30+, Granzyme B+, CD56-, ALK1-, EMA-. Alla biologia molecolare si rilevava riarrangiamento monoclonale del TCR-gamma. Il paziente \ue8 attualmente in trattamento con radioterapia locale. La diagnosi istologica e molecolare dei due casi descritti era orientativa per linfoma anaplastico a grandi cellule primitivo cutaneo CD8+ CD30+. In considerazione del polimorfismo clinico e della rapida evoluzione sistemica, tali casi potrebbero rappresentare un subset pi\uf9 aggressivo nel gruppo dei linfomi ALC primitivi della cute

Macrophage ferroportin is essential for stromal cell proliferation in wound healing

Iron recycling by macrophages is essential for erythropoiesis, but may be also relevant for iron redistribution to neighbouring cells at the local tissue level. Using mice with iron retention in macrophages due to targeted inactivation of the iron exporter ferroportin, we investigated the role of macrophage iron release in hair follicle cycling and wound healing, a complex process leading to major clinical problems, if impaired. Genetic deletion of ferroportin in macrophages resulted in iron deficiency and decreased proliferation in epithelial cells, which consequently impaired hair follicle growth and caused transient alopecia. Hair loss was not related to systemic iron deficiency or anemia, thus indicating the necessity of local iron release from macrophages. Inactivation of macrophage ferroportin also led to delayed skin wound healing with defective granulation tissue formation and diminished fibroplasia. Iron retention in macrophages had no impact on the inflammatory processes accompanying wound healing, but affected stromal cells proliferation, blood and lymphatic vessels formation, and fibrogenesis. Our findings reveal that iron/ferroportin plays a largely underestimated role in the macrophage trophic function in skin homeostasis and repair

Cutaneous extranodal NK/T-cell lymphoma: a clinicopathologic study of 5 patients with array-based comparative genomic hybridization

Extranodal natural killer/T-cell (ENK/T) lymphoma is a rare neoplasm, subcategorized into ENKITnasal ENK/T-N) and ENK/T-nasal type (ENK/T-NT) lymphomas. ENK/T-NT lymphoma with initial presentation in the skin is known as primary cutaneous (PC) ENK/T-NT lymphoma. Patients and methods: The aim ofthis study was to investigate pathogenesis, genomic alterations, and prognosis ofcutaneous ENK/T lymphomas to provide further insights into clinicopathologic features and genetic mechanism of lymphomagenesis. A retrospective case study of 5 white patients affected by ENK/T lymphoma (4 PC-ENK/T-NT and l ENKIT-N with cutaneous involvement) was performed. Results: Most ofthe cases presented with multiple nodular and ulcerated lesions localized on the extremities. A considerable percentage had disease in advanced stage at diagnosis with a 12-month survival rate of 40%. Genomic alterations were detected by array-based comparative genomic hybridization that showed gains of 1q, 7q and loss of 17p in the cases of PC-ENK/T-NT Iymphomas and gain of 7q and 10ss of 9p, 12p, 12q in the case of ENK/T-N lymphoma. Conclusion: ENK/T lymphoma is a very aggressive entity, and, in our cases, tbe exc1usively cutaneous presentation was not associated with a better prognosis. The results of our array comparative genomic hybridization analysis could be useful to better define the diffcrent ENK/T lymphoma subgroups with cutaneous involvement and new protocols of treatment