Cogan's syndrome: An autoimmune inner ear disease

ObjectivesThe objective of our study was to review our current knowledge of the aetiopathogenesis of Cogan's syndrome, including viral infection and autoimmunity, and to discuss disease pathogenesis with relevance to pharmacotherapy.Systematic review methodologyRelevant publications on the aetiopathogenesis and pharmacotherapy of Cogan's syndrome from 1945 to 2012 were analysed.Results and conclusionsCogan's syndrome is a rare autoimmune vasculitis, and its pathogenesis is unknown. Infection, but primarily autoimmunity, may play contributing roles in the pathogenesis of this disease. It is characterised by ocular and audiovestibular symptoms similar to those of Meniere's syndrome. Approximately 70% of patients have systemic disease, of which vasculitis is considered the pathological mechanism. The immunologic theory is based on the release of auto-antibodies against corneal, inner ear and endothelial antigens, and of anti-nuclear cytoplasmic auto-antibodies (ANCA).Corticosteroids are the first line of treatment, and multiple immunosuppressive drugs have been tried with varying degrees of success. Tumour necrosis factor (TNF)-alpha blockers are a category of immunosuppressive agents representing a recent novel therapeutic option in Cogan's syndrome.     

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions

During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available.     

Signals of cell death and tissue turnover during physiological pregnancy,pre-eclampsia,and autoimmunity

Apoptosis normally occurs in the human placenta. As a consequence, cell blebs, post-apoptotic debris (also referred to as syncytial knots) and membrane microparticles are released into the blood of pregnant women. These events become prominent during the best-characterized pregnancy complication, pre-eclampsia. An excessive or deregulated cell death, which results in the generation of an overwhelming burden of apoptotic material, alarms the immune system. This plays a role in the pathogenesis of systemic connective tissue diseases and possibly of small vessels vasculitis. Infiltration of leukocytes and activation of endothelial cells and platelets are hallmarks of normal pregnancy, indicating that physiologic pregnancy is a condition characterized by an activation of the innate immune system. Conversely, a failure in the physiologic termination of inflammatory events is probably a requirement for pre-eclampsia to develop. Here, we discuss recent findings suggesting a link between deregulated disposal of placental debris, the generation of endogenous pro-inflammatory signals (alarmins) and the widespread vascular inflammation that characterizes on one hand pre-eclampsia and on the other systemic autoimmune diseases.     

Mycotoxin Removal by Lactobacillus spp. and Their Application in Animal Liquid Feed

The removal of mycotoxins from contaminated feed using lactic acid bacteria (LAB) has been proposed as an inexpensive, safe, and promising mycotoxin decontamination strategy. In this study, viable and heat-inactivated L. acidophilus CIP 76.13T and L. delbrueckii subsp. bulgaricus CIP 101027T cells were investigated for their ability to remove aflatoxin B₁ (AFB₁), ochratoxin A (OTA), zearalenone (ZEA), and deoxynivalenol (DON) from MRS medium and PBS buffer over a 24 h period at 37 °C. LAB decontamination activity was also assessed in a ZEA-contaminated liquid feed (LF). Residual mycotoxin concentrations were determined by UHPLC-FLD/DAD analysis. In PBS, viable L. acidophilus CIP 76.13T and L. delbrueckii subsp. bulgaricus CIP 101027T cells removed up to 57% and 30% of ZEA and DON, respectively, while AFB₁ and OTA reductions were lower than 15%. In MRS, 28% and 33% of ZEA and AFB₁ were removed, respectively; OTA and DON reductions were small (≤15%). Regardless of the medium, heat-inactivated cells produced significantly lower mycotoxin reductions than those obtained with viable cells. An adsorption mechanism was suggested to explain the reductions in AFB₁ and OTA, while biodegradation could be responsible for the removal of ZEA and DON. Both viable LAB strains reduced ZEA by 23% in contaminated LF after 48 h of incubation. These findings suggest that LAB strains of L. acidophilus CIP 76.13T and L. delbrueckii subsp. bulgaricus CIP 101027T may be applied in the feed industry to reduce mycotoxin contamination.     

Validity and metric of MiniMental Parkinson and MiniMental State Examination in Parkinson’s disease

The MiniMental Parkinson (MMP) has been derived from the MiniMental State Examination (MMSE) for the screening of cognitive impairment in Parkinson’s disease by adding subtests that were focused on executive and visuo-spatial impairment more than on memory or language deficits. In this multicenter study, the psychometric and validity properties of the MMP have been evaluated in 69 cognitively intact and 52 cognitively impaired patients with Parkinson’s disease, classified according to their performance at the Dementia Rating Scale. The MMP showed better metrics and convergent validity, and higher screening ability. However, its performance was not fully satisfying in terms of data distribution, coefficient of variation and specificity, and Receiver Operating Characteristic curves did not show clear cut superiority of either scale at their best sensitivity–specificity trade off. The MMP seems to be slightly preferable to the MMSE only at a cut off that favours sensitivity with respect to specificity, for screening purposes. The test is simple and quick, but has limitations in terms of validity.