Central skull base osteomyelitis (SBO) is a life-threatening disease originating from ear and from sinonasal infections. The intention of this study was to evaluate contemporary trends in etiology, diagnosis, management, and outcome of SBO and to draw the clinician's attention on this probably underestimated disease. Over a 6-year period we performed this systematic study in an academic quaternary medical care and skull base center including 20 patients (mean age 63.7 years) with central SBO, which is one of the largest series from a single center. In contrast to previous studies we explicitly excluded infections limited to malignant external otitis only but did not restrict central SBO to conditions unrelated to aural pathology. Fifteen patients had otogenic and five sinugenic SBO; four patients had fungal or mixed fungal infections. Pre-existing illnesses altering bone vascularization were detected in 70 % of the patients and had a negative effect on the improvement of cranial nerve palsies that were found in 14 patients. In relation, patients with otogenic SBO more often had local and systemic predisposing factors. Contrary to previous studies 16 patients (80 %) underwent surgical therapy and none of our patients died. A meta-analysis of five recent studies was done and compared with our own data and two previous meta-analyses. The present study highlights several important aspects with major implications for diagnosis and treatment of SBO that have not been adequately addressed as yet. In contrast to the restrictive attitude towards surgery in literature we recommend early and radical operative treatment to reduce its mortality.
SummaryCyclophilin D (CYPD) is a mitochondrial peptidyl prolyl-cis,trans-isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wildtype with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging.
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