The therapeutic effects of Rho-ROCK inhibitors on CNS disorders

Rho-kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many aspects of neuronal functions including neurite outgrowth and retraction. The Rho-ROCK pathway becomes an attractive target for the development of drugs for treating central nervous system (CNS) disorders, since it has been recently revealed that this pathway is closely related to the pathogenesis of several CNS disorders such as spinal cord injuries, stroke, and Alzheimer’s disease (AD). In the adult CNS, injured axons regenerate poorly due to the presence of myelin-associated axonal growth inhibitors such as myelin-associated glycoprotein (MAG), Nogo, oligodendrocyte-myelin glycoprotein (OMgp), and the recently identified repulsive guidance molecule (RGM). The effects of these inhibitors are reversed by blockade of the Rho-ROCK pathway in vitro, and the inhibition of this pathway promotes axonal regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho-ROCK inhibitors have been demonstrated in animal models of stroke. In this review, we summarize the involvement of the Rho-ROCK pathway in CNS disorders such as spinal cord injuries, stroke, and AD and also discuss the potential of Rho-ROCK inhibitors in the treatment of human CNS disorders

Global Thrombosis Test - a possible monitoring system for the effects and safety of dabigatran

© Otsui et al. 2015BACKGROUND: Dabigatran is an alternative to warfarin (WF) for the thromboprophylaxis of stroke in patients with non-valvular atrial fibrillation (NVAF). The advantage of dabigatran over WF is that monitoring is not required; however, a method to monitor the effect and the safety of dabigatran is not currently available. The Global Thrombosis Test (GTT) is a novel method to assess both clot formation and lysis activities under physiological conditions. OBJECTIVE: The aim of this study was to evaluate whether treatment with dabigatran might affect shear-induced thrombi (occlusion time [OT], sec) by the GTT, and to investigate the possibility that the GTT could be useful as a monitoring system for dabigatran. PATIENTS/METHODS: The study population consisted of 50 volunteers and 43 NVAF patients on WF therapy, who were subsequently switched to dabigatran. Using the GTT, the thrombotic status was assessed one day before and 1 month after switching anticoagulation from WF to dabigatran. RESULTS: The OT was 524.9 ± 17.0 sec in volunteers whereas that of NVAF patients on WF therapy was 581.7 ± 26.3 sec. The switch from WF to dabigatran significantly prolonged OT (784.5 ± 19.3 sec). One patient on WF therapy and 12 patients on dabigatran therapy were shown to have OT > 900 sec. CONCLUSION: The GTT could be used to assess the risk of dabigatran-related bleeding complications.Peer reviewe

Interdisciplinary therapy for severe periodontitis with Angle Class II Division 1 malocclusion : A case report with 7-year follow-up

Background: Previous studies have suggested that occlusal discrepancy is a risk factor contributing to periodontal disease. 1-3 Occlusal discrepancy could increase the risk of infrabony defects. This is a case of a patient with severe periodontitis who exhibited many infrabony defects in the molar region due to malocclusion-induced trauma. Here, we report the 7-year prognosis of the patient after periodontal regenerative and comprehensive orthodontic therapies for functional recovery with implant prosthodontics. Case Description: A 54-year-old female presented with the chief complaint of masticatory disturbance. In the molar region, significant tooth mobility, deep periodontal pockets, and infrabony defects were observed. She had excessive overjet, resulting in collapse of anterior guidance. Malocclusion was considered to be an exacerbating factor of the infrabony defects. After initial periodontal therapy, we performed periodontal regenerative therapy in the mandibular molar regions. We carefully placed implants in a position in the maxillary molar region that would ensure an appropriate anterior dental relationship after orthodontic treatment. Comprehensive orthodontic treatment was subsequently performed using implants as anchoring units. Then, definitive surgery was performed on the mandibular molars before placing the final prosthesis. A favorable periodontal condition and a stable occlusion have been maintained for the 7-year post-treatment period. Practical Implications: Comprehensive and interdisciplinary treatment enables stable occlusion and establishment of periodontal tissue and peri-implant tissues with high cleansability, even in patients with severe periodontitis and malocclusion. In the present case, a favorable long-term treatment outcome can be expected

Evaluating temperature effects on leaching behavior of geogenic arsenic and boron from crushed excavated rocks using shaking and nonshaking batch tests

The leaching behavior of arsenic and boron is evaluated in this work through two types of excavated rocks with geogenic contaminants under different temperatures. Excavated rocks with geogenic contaminants are expected to be used in embankments with appropriate countermeasures being taken against the risks brought about by geogenic contamination. The leaching behavior might change because of changes in the ground temperature. However, the effects of temperature on the leaching behavior of such rocks have not been well examined. Herein, batch leaching tests at temperatures between 5 and 60 °C were performed under shaking and nonshaking conditions. Mudstone and shale rock were crushed into particles smaller than 2 mm, which were required for the tests. The tests were carried out for durations ranging from 6 h to 15 days because changes in leaching kinetics also require careful evaluation. After conducting the nonshaking tests for 15 days at 40 °C, the mudstone sample leached arsenic and boron at concentrations of approximately 0.7 and 1.0 mg/L, respectively. The arsenic and boron concentrations were about 20 and 40% higher than those of the sample leached at a temperature of 20 °C. Elevated temperatures were seen to increase the leaching kinetics of the toxic elements. For the shale rock sample, the leaching rate for arsenic was 7.7 × 10⁻²/h at 40 °C, which was about 2.5 times greater than the value at 30 °C. The nonshaking tests showed higher leaching amounts of arsenic and boron than the shaking tests, especially at elevated temperatures. As unrealistic estimations should be avoided, nonshaking tests are suggested. Moreover, nonshaking tests lasting longer than 6 h are necessary due to the relatively slow dissolution of minerals

Comprehensive treatment for severe periodontitis with pathologic tooth migration−related bimaxillary protrusion : A case report with 3-year follow-up

Background: Patients with severe periodontitis often experience pathologic tooth migration (PTM), which impairs esthetics and leads to occlusal disharmony (e.g., premature contacts and/or traumatic occlusion) that can further exacerbate periodontitis. Here, we describe a patient who exhibited severe periodontitis with PTM-related bimaxillary protrusion. This report includes 3-year clinical outcomes following periodontal regenerative therapy, implant-anchored orthodontic therapy, and implant prosthodontics intended to achieve both functional and esthetic improvements. Case Description: A 63-year-old woman presented with the chief complaint of upper anterior tooth mobility. Clinical examination revealed excessive tooth mobility, deep periodontal pockets, and infrabony defects in all teeth. All teeth exhibited PTM; the mandibular anterior teeth exhibited marked protrusion caused by the progression of periodontitis. After initial periodontal therapy, periodontal regenerative therapy was performed in all molar regions. At 9 and 6 months postoperatively, comprehensive orthodontic treatment was initiated for the mandible and maxilla, respectively, using orthodontic anchorage devices to achieve acceptable functional occlusion. After orthodontic treatment, staged guided bone regeneration was performed and dental implants were placed in the severely resorbed maxillary anterior ridge. This comprehensive treatment yielded favorable periodontal conditions, stable occlusion, and good esthetic outcomes. Practical Implications: Favorable esthetics, stable occlusion, and highly cleansable periodontal tissues were achieved with well-planned interdisciplinary and comprehensive treatment, although the patient had severe periodontitis and PTM-related bimaxillary protrusion