Metallothioneins (MTs) are small, cysteine-rich proteins which have been implicated in various forms of stress providing cytoprotective action against oxidative injury, DNA damage and apoptosis. Owing to their high affinity for physiological metals, such as zinc and copper MTs are also critical components of regulatory proteins involved in cell growth and multiplication, as well as in the maintenance of immune homeostasis. To elucidate the role of MTs in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MT I+II proteins and the content of free Zn ions in the brain, spinal cord and in the liver early in the course of chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) pathogenesis, i.e. before the onset of any clinical symptoms. Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control animals were treated with CFA alone. The data, obtained by immuno-histochemistry and in situ fluorescent labeling of free zinc ions, have shown that in the presymptomatic phase of CR-EAE (on the seventh postimmunization day) MTs I+II were markedly upregulated in the cells that form blood-brain and blood-cerebrospinal fluid barriers, as well as in the cerebellar parenchyma and hippocampal dentate gyri. Furthermore, we found that the liver also becomes a site of extensive MTs I+II synthesis shortly after immunization. Simultaneously, tissue content of free zinc ions increased at the sites of MTs induction, reflecting their antioxidative activity. The data, described in this paper point to regulatory and neuroprotective role of MTs in the pathogenesis of CR-EAE.

Gp96 (also known as glucose-regulated protein 94, endoplasmin) is the endoplasmic reticulum (ER)-resident protein, which belongs to the heat shock protein HSP90 family. It is upregulated in response to glucose starvation and other stressful stimuli that disrupt protein synthesis in the ER. There, it is acting as a molecular chaperon involved in the correction of unfolded proteins, in the activation of proteasome-dependent ER-associated degradation of the misfolded proteins, and in activation of protein translations that modulate the polypeptide traffic into the ER. In addition, it has been implicated in antigen presentation and MHC class I and II upregulation, in the activation and maturation of dendritic cells and proinflammatory cytokine secretion, as well as in chaperoning of integrins and Toll-like receptors, acting as a "danger signal" to the innate and adaptive immunity. Moreover, owing to its specific function in Ca2+ homeostasis and in the insulin– IGF/signaling pathways, it has been proposed that gp96 might participate in mechanisms that are critical for cell growth, differentiation, and responses to ER stress. Emphasizing that gp96, as a natural adjuvant for chaperoning antigenic self peptides into the immune surveillance pathways, may also be involved in the maintenance of morphostasis and self tolerance, in this survey we show that high levels of upregulation of gp96 in regenerating liver and thymus are followed by signs of transient autoimmunity, augmented apoptosis in thymus, and the presence of autoreactive NKT and regulatory T cells that might be involved in the control of rapid liver growth induced by partial hepatectomy.

Background: Sarcoidosis is an idiopathic multisystemic disease that affects young to middle aged adults, with higher incidence in women. Although it may involve the breast parenchyma, primary sarcoidosis of the breast is very rare. It occurs in less than 1% of cases. In a differential diagnosis it may potentially be considered a malignancy. Case Report: We report a case in which breast sarcoidosis was the first clinical manifestation of systemic disease in a 54-year-old woman who presented with wide erythematous skin changes associated with palpable induration. Considering the fact that physical examination and the results of mammography, ultrasound and magnetic resonance imaging were inconclusive and unable to rule out malignancy, biopsy was performed. Pathohistological diagnosis showed a non-necrotizing granulomatous inflammation without elements of breast cancer. Sarcoidosis was confirmed with elevated level of angiotensin-converting enzyme in the sera and characteristic chest multislice computed tomography findings. The bronchoalveolar lavage was infiltrated with lymphocytes. Conclusion: Breast sarcoidosis has diverse and nonspecific imaging characteristics. Carcinoma must always be excluded by core needle biopsy. Achieving correct diagnosis is mandatory so that adequate corticosteroid therapy can be applied as early as possible. A multidisciplinary approach is of utmost importance in the diagnostic workup.

A torsion of the vermiform appendix with a mesoappendiceal lipoma is a rare condition. It is also a rare cause of acute abdomen, as such, the condition is diagnosed during surgery. This case report presents a 70-year-old male patient with lower right abdominal pain and signs of acute abdomen with an increased peripheral blood leukocyte count. An ultrasound examination revealed a mass of 9.6 cm2, which was suggested to be a perityphlitic abscess. An emergency operation was indicated, as the patient had clinical signs of acute abdomen. Laparotomy via a pararectal incision revealed the cause of the pain to be a torsion of the vermiform appendix caused by a mesoappendiceal lipoma. The apex of the appendix was perforated, which caused circumscript peritonitis. Both an appendectomy and an extirpation of the tumor were performed, and a surgical drain was placed in the wound, yielding an excellent postoperative clinical outcome.