Histone deacetylase mediated transcriptional activation reduces proviral loads in HTLV-1 associated myelopathy/tropical spastic paraparesis patients

Epigenetic modifications of chromatin may play a role in maintaining viral latency and thus persistence of the human T-lymphotropic virus type 1 (HTLV-1), which is responsible for HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A major determinant of disease progression is increased peripheral blood proviral load (PVL), possibly via the accumulation of infected cells in the central nervous system (CNS) creating a damaging inflammatory response. Current therapeutic approaches that focus on reducing either cell proliferation, viral replication, or tissue invasion are still unsatisfactory. Contrasting with these inhibitory strategies, we evaluated the efficacy of a novel approach aimed, paradoxically, at activating viral gene expression to expose virus-positive cells to the host immune response. We used valproate (VPA), a histone deacetylase inhibitor that has been used for decades as a chronic, safe treatment for epileptic disorders. Based on in vitro and in vivo data, we provide evidence that transient activation of the latent viral reservoir causes its collapse, a process that may alleviate the condition of HAM/TSP. This represents the first such approach to treating HAM/TSP, using gene activation therapy to tilt the host-pathogen balance in favor of an existing antiviral response. This trial is registered at http://clinicaltrials.gov/as no. NCT00519181.     

Bisphosphonate‐related osteonecrosis of the jaws: analysis of a case series at a dental school

Bisphosphonate‐related osteonecrosis of the jaws (BRONJ) is an adverse effect of drugs used to treat bone metabolism diseases, such as osteoporosis and bone metastases. The present study retrospectively evaluated the clinical characteristics and evolution of BRONJ cases that were diagnosed and treated at a dental school from 2004 to 2011. During that period, 13 patients met the criteria of the study among a population of 2,342 patients with oral lesions. Of the 13 patients, 12 were females. Ten were intravenous bisphosphonate users, and nine had breast cancer as the primary disease. Eight mandibular cases were observed. Eight patients interrupted the use of the bisphosphonates temporarily during the treatment. Surgical treatment was conducted in 10 patients, which was associated with platelet‐rich plasma in six cases, which led to a regression to Stage I in 50% of these and cure in 33.3%. Of the total sample, four (30.8%) cases were cured, six (46.1%) regressed to Stage I, and three (23.1%) remained in Stage II after treatment. Dental rehabilitation occurred in seven patients. Dissemination of knowledge among professionals is essential for prevention and early diagnosis of BRONJ. Dental schools must act as reference centers and participate in the multidisciplinary care of bisphosphonate users.