C2C12 MYOBLASTS RELEASE MICRO-VESICLES CONTAINING mtDNA AND PROTEINS INVOLVED IN SIGNAL TRANSDUCTION

none11Micro-vesicles can be released by different cell types and operate as ‘safe containers’ mediatine inter-cellular communication. In this work we investigated whether cultured myoblasts could release exosomes. The reported data demonstrate, for the first time, that C2C12 myoblasts release micro-vesicles as shown by the presence of two exosome markers (Tsg101 and Alix proteins). Using real-time PCR analysis it was shown that these micro-vesicles, like other cell types, carry mtDNA. Proteomic characterization of the released micro-vesicle contents showed the presence of many proteins involved in signal transduction. The bioinformatics assessment of the Disorder Index and Aggregation Index of these proteins suggested that C2C12 micro-vesicles mainly deliver the machinery for signal transduction to target cells rather than key proteins involved in hub functions in molecular networks. The presence of IGFBP-5 in the purified micro-vesicles represents an exception, since this binding protein can play a key role in the modulation of the IGF-1 signalling pathway. In conclusion, the present findings demonstrate that skeletal muscle cells release micro-vesicles, which probably have an important role in the communication processes within skeletal muscles and between skeletal muscles and other organs. In particular, the present findings suggest possibile new diagnostic approaches to skeletal muscle diseases.openM. GUESCINI; D. GUIDOLIN; L. VALLORANI; L. CASADEI; A.M. GIOACCHINI; P. TIBOLLO; M. BATTISTELLI; E. FALCIERI; L. BATTISTIN; L.F. AGNATI; V. STOCCHIGuescini, Michele; D., Guidolin; Vallorani, Luciana; Casadei, Lucia; Gioacchini, ANNA MARIA; P., Tibollo; Battistelli, Michela; Falcieri, Elisabetta; L., Battistin; L. F., Agnati; Stocchi, Vilbert

Vascular cognitive disorder. A biological and clinical overview

Although vascular dementia (VaD) represents the second most common cause of dementia after Alzheimer's disease (AD) in the elderly, and is referred as the "silent epidemic of the twenty-first century", there is still a controversy on terminology, classification and diagnostic criteria of VaD. The diagnosis of VaD resides in clinical criteria determining a cognitive impairment, the presence of cerebrovascular disease and, only in the case of post-stroke dementia or multi-infarct dementia, a temporal relationship between these. The search for a reliable biochemical tests helping in the diagnosis of VaD is so far not available. Several vascular risk factors have a role in the development of VaD and their identification and treatment are among the major aspects of management of VaD. A new line of research in this field is the study of genetic factors underlying vascular cognitive impairment which are: (1) genes predisposing to cerebrovascular disease, and (2) genes that influence brain tissue responses to cerebrovascular lesions. Evidence in favour of a coexistence of vascular and degenerative components in the pathogenesis of dementia in an elderly population comes from neuropathological and epidemiological studies. There is now a great debate whether VaD and AD are more than common coexisting unrelated pathologies and, instead, represent different results of synergistic pathological mechanisms. Preventive approaches aiming at reducing incident VaD by targeting patients at risk of cerebrovascular disease (primary prevention), or acting on patients after a stroke (secondary prevention) to prevent stroke recurrence and the progression of brain changes associated with cognitive impairment are mandatory therapeutic strategies

Vascular Dementia

Although vascular dementia (VaD) represents the second most common cause of dementia after Alzheimer\u2019s disease (AD) in the elderly, and is referred to as the \u2018\u2018silent epidemic of the twenty\u2010first century,\u2019\u2019 there is still a controversy on terminology, classification, and diagnostic criteria of VaD. The diagnosis of VaD resides on diagnostic clinical criteria determining (1) a cognitive impairment, (2) the presence of cerebrovascular disease, and (3) specifically in poststroke or multi\u2010infarct dementia, a temporal relationship between these. The search for a reliable biochemical test helping in the diagnosis of VaD is so far not available. Several vascular risk factors have a role in the development of VaD and their identification and treatment are among the major aspects of VaD management. A new line of research in this field is the study of genetic factors underlying vascular cognitive impairment which are: (1) genes predisposing to cerebrovascular disease, and (2) genes that influence brain tissue responses to cerebrovascular lesions. Evidence in favor of a coexistence of vascular and degenerative components in the pathogenesis of dementia in an elderly population comes from neuropathological and epidemiological studies. There is now a great debate whether VaD and AD are more than common coexisting unrelated pathologies or, instead, represent different results of synergistic pathological mechanisms. Current available medications for the treatment of VaD include acetylcholinesterase inhibitors for mild to moderate cases, and memantine, an NMDAreceptor antagonist. However, therapeutic preventive approaches aiming at reducing incident VaD by targeting patients at risk of cerebrovascular disease (primary prevention), or acting on patients after a stroke (secondary prevention) to prevent stroke recurrence and the progression of brain changes associated with cognitive impairment are the mandatory strategies

Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum

We describe a 28-year-old woman affected by migraine without aura according to the ICHD-2 criteria who manifested with seizures as presenting symptom of a serotonin syndrome characterized by mild and transient fever and subtle postural hand tremor. Few days later she developed an acute rhabdomyolysis with associated increased D-dimer and liver enzymes. The condition was precipitated by triptans use. Chronic therapy with fluoxetine, taken to treat an eating disorder, and the use of a self-prescribed herbal medication containing hypericum predisposed to a serotonergic hyperstimulation. This case report calls attention on the importance to avoid multidrug regimens for the prevention of serotonin syndrome that can present with atypical symptoms and may worsen with severe acute rhabdomyolysis