Clinical Features, ARIX and PHOX2B Nucleotide Changes in Three Families with Congenital Superior Oblique Muscle Palsy

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G&#62;A, in the 5’-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. 1 and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G&#62;A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.</p

Metallothionein contributes to neuropathic pain in partial sciatic nerve ligated rats

Neuropathic pain is a chronic pain state caused by nerve injury or diseases. The symptoms involve spontaneous pain, hyperalgesia and allodynia. Neuropathic pain develops by the mechanisms both central nervous system and peripheral nervous system. Moreover,both neuronal cells and glia cells are involved in the development of neuropathic pain. However, the pathogenic mechanism of neuropathic pain is not clearly understood. We previously reported that metallothionein lacked in peripheral nerve from patients of complex regional pain syndrome by proteomic approach. In this report, we examined whether the level of metallothionein (MT) is changed in partial sciatic nerve ligation (PSL) rats as the model animal of neuropathic pain and the administration of metallothionein affects behavior against physical and thermal stimulus to PSL rats. MT-I/II expression was gradually decreased in the distal region of the injury site. At day 28, MT-I/II expression was markedly decreased in both proximal and distal region at the same level. The administration of MT signifi cantly improved allodynia and thermal hyperalgesia comparing to the administration of PBS. Moreover,GAP43, a marker protein of nerve regeneration, increased in the distal region and g lial fibrillar acidic protein, a marker protein of infl ammation, decreased in the proximal region of the injury site. These results suggest that metallothionein is deeply related to occurrence of neuropathic pain and regeneration of the injured nerve in PSL rats.departmental bulletin pape

Periodontal Tissue Regeneration Using Fibroblast Growth Factor -2: Randomized Controlled Phase II Clinical Trial

Background: The options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF)-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation. Methodology/Principal Findings: We used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC) as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured ?3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC cotaining 0.1% FGF-2; and Group H, given HPC Containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 μL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021) in rate of increase in alveolar bone height was identified between Group P (23.92%) and Group H (58.62%) at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132). No serious adverse events attribute to the investigational drug were identified. Conclusions: Although no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021) between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration of periodontal tissue in patients with periodontitis