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Objectives: The goal of this study was to investigate the role of nitric oxide synthase (NOS) in occlusal force-induced signal transduction in rat periodontal ligament (PDL).Design: Rats were fitted with a bite plate and a metal cap to the maxillary and mandibular incisors, respectively, to eliminate the occlusal forces on rat molars. One group was sacrificed at 7 days (exclusion group), while the remaining rats had their appliances removed to reestablish molar occlusal contact (reload group) and were sacrificed 7 days thereafter. Another group of rats (normal group) were left completely untreated. Frozen cross sections of the upper first molars were stained with NADPH-diaphorase to quantify NOS activity. The distal sides of the disto-palatal roots of the upper first molars were examined, and the number and the area of stained cells in the PDL were measured.Results: In the normal group, NOS expression was detected in blood vessels, monocyte-macrophages, fibroblastic cells and osteoclastic cells. NOS expression was lower in the exclusion group when compared with the normal group or the reload group (p < 0.05), and the exclusion group exhibited occluded blood vessels and a narrowing of PDL. In contrast, in the reload group the PDL and blood vessel structure had recovered and NOS expression was increased to the level of the controls.Conclusion: Occlusal force resulted in increased NOS expression. NO may mediate changes in PDL structure in response to occlusal force. [ABSTRACT FROM AUTHOR]

The relationship between occlusal stimuli and a hypofunctional periodontal ligament (PDL) structure has been reported, though changes in occlusal recovery conditions were still unclear. Nitric oxide (NO) produced by NO synthase (NOS) is considered a factor for vascular and immune system control, and it increases according to mechanical stimuli. The objective of this study was to examine the relationship between NOS and occlusal stimuli in PDL by comparing hypofunction with occlusal recovery. The study focused on the expression of endothelial NOS (eNOS) and inducible NOS (iNOS). Their expression significantly decreased in occlusal hypofunction compared with the control group and increased close to normal in an occlusal recovery group. The change in the immunopositive area was more dramatic than the immunopositive cell number. Moreover, the rate of iNOS increase was higher than that of eNOS. This study suggests that NO plays an important role in the recovery of the hypofunctional PDL. [ABSTRACT FROM AUTHOR]

Aim: To examine the effects of inactive periods of force on the amount of tooth displacement and root resorption during experimental tooth movement in rats. Sample: Sixty 11-week-old male Sprague-Dawley rats. Method: The maxillary first molar (M1) was moved mesially using a removable titanium-nickel alloy closed coil spring for 14 days. The rats were divided into four groups with, 0, 1, 4, and 9 hours of inactivation per day. Results: Tooth displacement in the 0- and 1-hour groups was significantly greater than that in the 9-hour group. The area of root resorption in the 4- and 9-hour groups was significantly less than that in the 0- and 1-hour groups. There was no significant difference in root resorption between 0- and 1-hour groups, and also between 4- and 9-hour groups. Conclusion: The distance of tooth displacement gradually decreased as the inactive period increased, whereas root resorption suddenly decreased between 1 and 4 hours of inactive orthodontic force. [ABSTRACT FROM AUTHOR]

Aim: To investigate light forces for experimental tooth movement. Method: Light orthodontic forces of 1.2, 3.6, 6.5, and 10 g force (gf) were applied for 14 days to move rat molars, and the effects of the forces on the rate of tooth movement and changes of the periodontium were examined. Results: In the early period, despite the different levels of force used in each group, there were no significant differences in tooth displacement. From hour 56 to day 14, the tooth displacement in the 1.2 gf group was significantly smaller than that in the other groups and the rate was nearly constant. The rates of tooth displacement in the 3.6, 6.5, and 10 gf groups fluctuated repeatedly, while the orthodontic forces gradually decreased. Conclusion: Experimental tooth movement in rats, tipping without friction under light forces, were either constant or fluctuated in cycles of several days' duration. This is in contradiction to the three-phases-theory of tooth movement described in previous investigations using heavy forces. [ABSTRACT FROM AUTHOR]

Expressions of immunophilin FKBP-12 and FKBP-52 were examined in the spinal cord of transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) gene. The immunoreactivity of FKBP-12 was present predominantly in the cytoplasm, but did not show a difference between age-matched wild type and transgenic (Tg) mice at 25 and 35 weeks. In contrast, the immunoreactivity of FKBP-52 was predominantly present in the nucleus, which progressively declined only in the Tg mice as early as an early presymptomatic stage at 25 weeks of age in the anterior horn neurons. The present result suggests that the downregulation of FKBP-52 may be involved in the pathogenesis in the early stages of amyotrophic lateral sclerosis (ALS). [Copyright &y& Elsevier]

GNE myopathy is an extremely rare genetic disorder caused by mutations in the GNE gene, resulting in reduced sialic acid synthesis and progressive muscle weakness. So far, no established treatment has been identified. For the replacement therapy of aceneuramic acid, extended-release formulation of aceneuramic acid (SA-ER) tablets have been developed. To evaluate the efficacy and safety of SA-ER for GNE myopathy, phase II/III study and the efficacy confirmation study were performed in Japan. These studies involved patients genetically diagnosed with GNE myopathy, allocated in SA-ER and placebo group (n=16:4 in Ph II/III, and n=10:4 in confirmation study, respectively). The evaluation of efficacy includes the primary endpoint of changes in upper extremity composite (UEC) score, with the secondary endpoint including GNE myopathy functional activity scale (GNEM-FAS). In the phase II/III study, the mean change in UEC at Week 48 was as small as -0.1 ± 3.7 kg in the SA-ER group versus -5.1 ± 3.4 kg in the placebo group with significant difference in two groups (P=0.0013) in the generalized estimating equation test repeated measurement analysis. The least squares mean (LSM) difference (95% CI) between the groups was 4.8 kg (-0.3 to 9.9; P=0.0635). Also, in the efficacy confirmation study, decrease in LSM change in UEC score at Week 48 with SA-ER (-0.115 kg) was numerically smaller as compared with placebo (-2.625 kg), with LSM difference (95% confidence interval) of 2.510 (-1.720 to 6.740) kg. Additionally, plots of GNEM-FAS upper extremity, mobility and total scores separated from each other between the SA-ER group and the placebo group. No clinically significant adverse events were observed in either study. Two sets of trial reproducibly showed a trend towards slowing of loss of muscle strength and function with orally administered SA-ER, indicating supplementation with sialic acid might be a promising replacement therapy for GNE myopathy. Aceneuramic acid received manufacturing and marketing approval in March 2024 following Pharmaceuticals and Medical Devices Agency (PMDA)'s review. [ABSTRACT FROM AUTHOR]