ABSTRACT
Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues. NAMPT expression was also increased in lipopolysaccharide- and proinflammatory cytokine-stimulated primary cultured human gingival fibroblasts (GF). Adenovirus-mediated NAMPT (Ad-Nampt) overexpression upregulated the expression and activity of COX-2, MMP1 and MMP3 in human GF. The upregulation of IL-1β- or Ad-Nampt-induced catabolic factors was significantly abrogated by the intracellular NAMPT (iNAMPT) inhibitor, FK866 or by the sirtuin (SIRT) inhibitor, nicotinamide (NIC). Recombinant NAMPT protein or extracellular NAMPT (eNAMPT) inhibition using a blocking antibody did not alter NAMPT target gene expression levels. Moreover, intragingival Ad-Nampt injection mediated periodontitis-like phenotypes including alveolar bone loss in mice. SIRT2, a part of the SIRT family, was positively associated with NAMPT actions in human GF. Furthermore, in vivo inhibition of the NAMPT-NAD⁺-SIRT axis by NIC injection in mice ameliorated the periodontal inflammation and alveolar bone erosion caused by intragingival injection of Ad-Nampt. Our findings indicate that NAMPT is highly upregulated in human GF, while its enzymatic activity acts as a crucial mediator of periodontal inflammation and alveolar bone destruction via regulation of COX-2, MMP1, and MMP3 levels.
Subject(s)
Animals , Humans , Mice , Adipokines , Alveolar Bone Loss , Fibroblasts , Gene Expression , Gingiva , Inflammation , Niacinamide , Nicotinamide Phosphoribosyltransferase , Periodontal Diseases , Periodontitis , Phenotype , Up-RegulationABSTRACT
Treatment of pain related to various types of deafferentation remains a neurosurgical challenge. Medical therapy and conventional surgical techniques for pain relief have not been effective due to this problem. Six patients with intractable pain following a brachial plexus injury were treated with dorsal root entry zone(DREZ) lesions. These lesions were made with CO2 laser. All patients were followed from 5 months to 5 years after surgery. Two-third of the patients were relieved of more than 50% of their preoperative pain. Post-operative neurosurgical complications were ipsilateral leg weakness and loss of proprioception in 2 cases. The laser technique is exact, makes uniform lesion, shortens the duration of the procedure, lessens cord manipulation and makes shalow penetration into the surrounding spinal cord. Dorsal root entry zone(DREZ) lesions made with CO2 laser appeared to be a satisfactory treatment for brachial plexus injury patients who have failed to respond to more conservative modes of therapy.
Subject(s)
Humans , Brachial Plexus , Causalgia , Lasers, Gas , Leg , Pain, Intractable , Proprioception , Spinal Cord , Spinal Nerve RootsABSTRACT
The authors report three cases of ossification of ligamentum flavum causing thoracic myelopathy. The symptoms of all cases were numbness in the legs and feet and motor weakness. Preoperative diagnosis were simple spine X-ray, metrizamide CT and magnetic resonance imaging. There was satisfactory improvement in all cases after total laminectomy and medial facetectomy.