Comparison of the skeletal stability after mandibular counter-clockwise rotation in three surgical procedures.

The treatment of mandibular deformities with an anterior open bite is challenging. In this study, skeletal stability after mandibular osteotomies was evaluated to determine the best treatment for mandibular prognathism with an anterior open bite in three procedures: intraoral vertical ramus osteotomy (IVRO), conventional sagittal split ramus osteotomy (conv-SSRO), and SSRO without bone fixation (nonfix-SSRO). Patients who underwent mandibular osteotomy to correct skeletal mandibular protrusion were included. Changes in skeletal and soft tissues were assessed using lateral cephalograms taken before (T1), 3 ± 2 days (T2), and 12 ± 3 months (T3) after surgery. Thirty-nine patients were included: nine in the IVRO group and 11 and 19 in the conv- and nonfix-SSRO groups, respectively. The mandibular plane angles (MPAs) of the T2-T1 were - 2.7 ± 2.0 (p = 0.0040), - 3.7 ± 1.7 (p < 0.0001), and - 2.3 ± 0.7 (p < 0.0001) in the IVRO, conv-SSRO, and nonfix-SSRO groups, respectively. The skeletal relapse of the MPAs was not related to the MPA at T2-T1, and it was approximately 1.3° in the conv-SSRO group. The skeletal relapse of the MAPs was significantly correlated with the MPA of T2-T1 in the IVRO (p = 0.0402) and non-fix-SSRO (p = 0.0173) groups. When the relapse of the MPAs was less than 1.3°, the MPA of T2-T1 was calculated as 2.5° in the nonfix-SSRO group. When the MPA of T2-T1 is less than 2.5°, non-fix SSRO may produce a reliable outcome, and when it is more than 2.5°, conv-SSRO may produce better outcomes.

Occlusal Plane Angle as a Key Factor for Chin Protrusion After Mandibular Osteotomy in Skeletal Class III.

There is no treatment algorithm to decide whether maxillomandibular or mandibular osteotomy alone should be performed in borderline cases. This study assessed the factors that affect the changes in soft tissue after mandibular setback. Patients who underwent mandibular osteotomy alone to correct mandibular protrusion were included in this study. Hard and soft tissue analyses were performed on lateral cephalograms before and 12±3 months after surgery. The popular points were set for referencing hard and soft tissues on the lateral cephalogram. Nasolabial, labiomental, and soft tissue facial plane angles were measured for the soft tissue assessment. To assess the mandibular setback amount, SNB was calculated. Twenty-one patients were included in this study. The nasolabial angle was increased after surgery and its change significantly correlated with the change in SNB ( P =0.00815). The change in soft tissue facial plane angle after surgery per change in SNB significantly correlated with the occlusal plane angle ( P =0.0009). An occlusal plane angle of at least 15.45 degrees was required for the SNB and soft tissue facial plane angle to change to the same degree. The occlusal plane angle (whether or not it was ≥15.45 degrees) may help in determining the surgical approach in borderline cases, specifically on whether maxillomandibular or mandibular osteotomy alone should be performed if the mandibular setback is simple.

Effects of anti-mouse RANKL antibody on orthodontic tooth movement in mice.

Background/purpose: Orthodontic tooth movement is achieved by alveolar bone remodeling, and therefore the balance of bone resorption and formation is important. Receptor activator of nuclear factor-κB ligand (RANKL) plays a crucial role in bone resorption. We previously reported that tumor necrosis factor-α (TNF-α) is also important in bone resorption during tooth movement. In this study, we focused on bone and root resorption during orthodontic tooth movement in mice using anti-mouse RANKL antibody (anti-mRANKL ab). Materials and methods: Anti-mRANKL ab was administered intraperitoneally to mice that subsequently underwent orthodontic tooth movement. After 10 days, tissues around the moved teeth were histologically evaluated. To confirm the effects of anti-mRANKL ab on TNF-α induced bone resorption, TNF-α was administered with and without anti-mRANKL ab into the supracalvaria and the sutures of the calvaria were histologically evaluated. Results: Orthodontic tooth movement was suppressed in mice treated with anti-mRANKL ab. Root resorption was observed after orthodontic tooth movement, but not in mice treated with anti-mRANKL ab. In the calvarial experiment, the number of TRAP-positive cells in the calvarial sutures was lower in mice administered TNF-α with anti-mRANKL ab than in mice administered TNF-α alone. Conclusion: Our findings suggest that anti-mRANKL ab suppressed orthodontic tooth movement. This needs to be considered when orthodontic tooth movement is required in patients using anti-RANKL antibody.

Effect of masseter muscle mass on the rate of experimental tooth movement in rats.

BACKGROUND: Previous clinical observational studies have suggested that orthodontic tooth movement (OTM) is related, at least partly, to the mass and/or capabilities of the masticatory muscles. OBJECTIVES: Our study aimed to examine the influence of masticatory muscle mass on the OTM in an animal experimental model in which the masseter muscle was modulated by botulinum neurotoxin type A (BTX) injection. METHODS: Eighteen Wistar rats were equally divided into two groups: BTX injection and control. BTX was injected bilaterally into the masseter muscles. Three days after the injection, the maxillary left first molars were orthodontically moved for 14 days. At the end of the experiment, micro-computed tomography was performed to evaluate the rate of OTM and bone morphometry. The masseter muscles were weighed and prepared for histological analyses. RESULTS: The masseter muscle mass in the BTX group was less than that in the control group, and histological findings showed atrophy of muscle fibres. The rate of OTM was significantly higher in the BTX group than in the control group. Furthermore, a negative correlation was detected between masseter muscle mass and OTM in the BTX group. Bone morphometry showed no difference between the control and BTX groups. CONCLUSION: Decreased masseter muscle mass was found to be closely related to an increase in the rate of OTM in rats using BTX injection to modify the masseter muscle mass. Masseter muscle mass could be a predictive factor for OTM in rats injected with BTX.

Impact of Chronic Kidney Disease on the Associations of Cardiovascular Biomarkers With Adverse Outcomes in Patients With Suspected or Known Coronary Artery Disease: The EXCEED-J Study.

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high-risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3-point MACE (3P-MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, cardiovascular death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt-1, NT-proBNP, and hs-cTnI, but not other biomarkers, were significantly associated with 3P-MACE, all-cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT-proBNP and hs-cTnI. NT-proBNP and hs-cTnI were also significantly associated with 5P-MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT-proBNP and hs-cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT-proBNP and hs-cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Soluble vascular endothelial growth factor receptor 2 and prognosis in patients with chronic heart failure.

AIMS: Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR-2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR-2 (sVEGFR-2) levels is associated with poor prognosis in patients with chronic heart failure (HF). METHODS AND RESULTS: We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR-2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all-cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR-2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow-up, 113 cardiovascular deaths, 211 all-cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein], a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16-2.74] and all-cause death (HR, 1.43; 95% CI, 1.04-1.94), but not with MACE (HR, 1.11; 95% CI, 0.86-1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78-1.35). The stratified analyses revealed that a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07-2.85) and all-cause death (HR, 1.49; 95% CI, 1.03-2.15) in the high-NT-proBNP group (above the median), but not in the low-NT-proBNP group. Notably, the patients with high-NT-proBNP and low-sVEGFR-2 (below the 25th percentile) had a 2.96-fold higher risk (95% CI, 1.56-5.85) for cardiovascular death and a 2.40-fold higher risk (95% CI, 1.52-3.83) for all-cause death compared with those with low-NT-proBNP and high-sVEGFR-2. CONCLUSIONS: A low sVEGFR-2 value was independently associated with cardiovascular death and all-cause death in patients with chronic HF. These associations were pronounced in those with high NT-proBNP levels.

Predisposing conditions for condylar sag after intraoral vertical ramus osteotomy.

Intraoral vertical ramus osteotomy (IVRO) is used to treat mandibular prognathism and temporomandibular disorders. However, the improvement of temporomandibular disorders after IVRO is considered to be due to the anterior and downward movement of the mandibular condyle, which may lead to condylar sag, and in the worst case, condylar luxation. In this retrospective cohort study, we examined factors potentially associated with condylar sag. Univariate analysis indicated that condylar sag was significantly associated with the following factors: magnitude of setback (P = 0.001), less than 3 mm setback (P < 0.001), presence of temporomandibular joint (TMJ) symptoms (P = 0.002), Wilkes classification (P = 0.039), occlusal cant correction ≥ 2 mm (P = 0.018), and mandibular condyle deformation (P < 0.001). Setback magnitude (P = 0.032) and TMJ symptoms (P = 0.007) remained significant in the multivariate analysis. In the receiver operating characteristic curve, the setback magnitude cut-off value for condylar sag after IVRO was 3.25 mm. Thus, the incidence of condylar sag after IVRO is increased with a smaller setback magnitude (≤ 3.25 mm) and the presence of TMJ symptoms. These factors should be evaluated by surgeons during treatment planning for IVRO to estimate condylar sag, and it may be possible to predict the risk of condylar luxation.

Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study.

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Biomechanical considerations for uprighting impacted mandibular molars.

This case report demonstrates two different uprighting mechanics separately applied to mesially tipped mandibular first and second molars. The biomechanical considerations for application of these mechanisms are also discussed. For repositioning of the first molar, which was severely tipped and deeply impacted, a novel cantilever mechanics was used. The molar tube was bonded in the buccolingual direction to facilitate insertion of a cantilever from the buccal side. By twisting the distal end of the cantilever, sufficient uprighting moment was generated. The mesial end of the cantilever was hooked over the miniscrew placed between the canine and first premolar, which could prevent exertion of an intrusive force to the anterior portion of the dentition as a side effect. For repositioning of the second molar, an uprighting mechanics using a compression force with two step bends incorporated into a nickel-titanium archwire was employed. This generated an uprighting moment as well as a distal force acting on the tipped second molar to regain the lost space for the first molar and bring it into its normal position. This epoch-making uprighting mechanics could also minimize the extrusion of the molar, thereby preventing occlusal interference by increasing interocclusal clearance between the inferiorly placed two step bends and the antagonist tooth. Consequently, the two step bends could help prevent occlusal interference. After 2 years and 11 months of active treatment, a desirable Class I occlusion was successfully achieved without permanent tooth extraction.

Distinct Characteristics of VEGF-D and VEGF-C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background VEGF-D (vascular endothelial growth factor D) and VEGF-C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF-C level is inversely and independently associated with all-cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF-D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF-D was measured. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-I, and high-sensitivity C-reactive protein), and VEGF-C, the VEGF-D level was significantly associated with all-cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF-D, either alone or in combination with VEGF-C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all-cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF-D value seems to independently predict all-cause mortality.

Anterior relapse or posterior drift after intraoral vertical ramus osteotomy.

This study aimed to evaluate the factors contributing to postoperative anterior relapse or posterior drift of the distal segment after intraoral vertical ramus osteotomy. A retrospective cohort study was conducted which included 31 patients who underwent setback surgery for mandibular prognathism by the intraoral vertical ramus osteotomy technique. Uni- and multivariate analyses were performed to determine the association of potential explanatory variables (sex, age, magnitude of setback, differences in setback magnitude between sides (right/left), duration of splint use, Angle's classification of malocclusion, mandibular angle, and tightness of occlusion of the molars) with positional changes in the distal segment. The setback magnitude was only significant factor affecting (P = 0.015) for posterior drift, with significant posterior in setback magnitudes of less than 7.25 mm. Posterior drift after intraoral vertical ramus osteotomy is less likely if setback magnitude exceeds 7.25 mm. For setbacks less than 7.25 mm, posterior drift should either be carefully corrected postoperatively, or an alternative surgical technique should be used. The setback magnitude showed a significant association with the risk of posterior drift following intraoral vertical ramus osteotomy, and the determined cut-off value may serve as a predictor for postoperative outcomes.

Prognostic role of bronchial asthma in patients with heart failure.

There are few reports investigating the relationship between bronchial asthma (BA) and heart failure (HF). We hypothesized BA may have impact on prognosis in patients with HF. Among 323 consecutive outpatients with HF, 191 patients without chronic obstructive pulmonary disease were analyzed. Twenty patients had BA, most of whom (80.0%) had preserved left ventricular ejection fraction (LVEF ≥ 50%). The use of ß-blockers was less frequent (55.0% vs 83.0%. p = 0.01), systolic blood pressure (133 ± 22 vs 120 ± 17 mmHg, p = 0.003), and heart rate (83 ± 14 vs 74 ± 15 bpm, p = 0.02) were higher in patients with BA than those without BA. During median follow up of 24 months, 45 (23.6%) experienced primary outcome defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unexpected hospitalization due to HF. Multivariate Cox regression analysis revealed that the presence of BA was independently associated with the occurrence of primary outcome (hazard ratio 3.08, 95% CI 1.42-6.71, p = 0.004). In the subgroup analysis of patients with preserved LVEF, patients with BA exhibited worse outcomes (p = 0.03 by log-rank). Patients with HF complicated by BA, most of whom had preserved LVEF, exhibited worse outcomes than those without BA.

Effects of the changes in the condylar long axis angle and condylar position on temporomandibular symptoms after intraoral vertical ramus osteotomy: a preliminary study.

OBJECTIVE: This study was conducted to characterize the effects of the changes in the condylar long axis and position on temporomandibular symptoms with respect proximal segment position after intraoral vertical ramus osteotomy (IVRO). STUDY DESIGN: Twenty Japanese patients with diagnosed jaw deformity underwent IVRO without internal fixation. Long-term changes in condylar long axis and position were assessed during postoperative follow-up examinations by using computed tomography, and t tests were performed for comparison. In addition, changes in temporomandibular symptoms were examined. RESULTS: The degree of axial rotation of the proximal segment changed significantly when the proximal segment was located laterally. Downward changes in condylar position significantly differed when the proximal segment was located posterolaterally. Forward changes in condylar position significantly differed when the proximal segment was located laterally; moreover, when the proximal segment was located laterally, temporomandibular symptoms disappeared. CONCLUSIONS: Lateral location of the proximal segment may be an important factor in the positive effects of IVRO, with respect to temporomandibular symptoms.

Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study.

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1ß, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

VEGF-C and Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor-C ( VEGF -C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF -C. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF -C levels were significantly and inversely associated with all-cause death (hazard ratio for 1- SD increase, 0.69; 95% confidence interval, 0.60-0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53-0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72-1.01). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF -C levels further improved the prediction of all-cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF -C value may independently predict all-cause mortality.

Time course of restenosis with "black hole" on intravascular ultrasound after implantation of platinum-chromium everolimus-eluting stent: Assessment using optical frequency-domain imaging.

Management of in-stent restenosis (ISR) remains challenging even in the drug-eluting stent era. We report the case of a Japanese female with repeated ISR after primary percutaneous coronary intervention (PCI) for acute coronary syndrome. We observed ISR tissue with "black hole" on intravascular ultrasound, which appeared to be heterogeneous tissue on optical frequency-domain imaging (OFDI). Paclitaxel-coated balloon dilatation of the ISR lesion with "black hole" was ineffective. The morphological assessment of ISR tissue using OFDI might be important to treat ISR lesions by PCI. OFDI is a novel tool to observe the difference in the in-stent tissue characteristics. .

Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats.

OBJECTIVE: To investigate the influence of lithium chloride (LiCl) on orthodontic tooth movement (OTM), orthodontically induced root resorption (OIRR), and bone morphometry. MATERIALS AND METHODS: Ten-week-old female Sprague Dawley rats (n = 32) were divided into four groups based on the concentration of LiCl administered daily per kilogram body weight: 0 (control group), 0.32, 0.64, and 1.28 mM/kg body weight. The maxillary left first molars were moved mesially by a 10 cN coil spring for 14 days. Micro-computed tomography, scanning electron microscope, and scanning laser microscope images were taken to measure the amount of OTM, the volume of OIRR, and bone morphometry. RESULTS: OIRR clearly decreased depending on the amount of LiCl administered, although OTM moderately decreased. The tooth inclined mesially and the root apex moved distally in the control and 0.32 mM groups. On the other hand, the tooth inclination angle became smaller and the root apex moved mesially in the 0.64 and 1.28 mM groups. In bone morphometry, the cortical bone mineral content and bone volume increased because of LiCl administration, and the trabecular bone measurements decreased. OIRR negatively correlated to the cortical bone measurements, and the amount of OTM significantly correlated to the cortical bone morphometry. CONCLUSIONS: In rats, LiCl reduced OIRR, which induced mesial movement of the tooth root apex. OIRR positively correlated to cortical bone morphometry.

Late gadolinium enhancement on cardiac magnetic resonance imaging is associated with coronary endothelial dysfunction in patients with dilated cardiomyopathy.

Myocardial fibrosis and coronary endothelial dysfunction are important determinants of outcome in patients with heart failure. However, the relationship of these factors in patients with dilated cardiomyopathy (DCM) is not fully understood. This study aimed to investigate the relationship between endothelium-dependent coronary vasomotor abnormality and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in patients with DCM. We examined 38 consecutive patients with DCM. All patients underwent CMR and the acetylcholine (ACh) provocation test using cardiac catheterization. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations, and quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. LGE was detected in 17 (44.7%) patients. The lactate extraction ratio (LER) in the ACh provocation test was significantly decreased in the LGE-positive group (before vs after ACh, 18.6 ± 13.6 vs - 13.3 ± 24.8%; p < 0.001) and in the LGE-negative group (before vs after ACh, 14.2 ± 19.5 vs 3.3 ± 16.2%; p = 0.02). The rate of patients with an LER < 0% (indicating myocardial lactate production due to myocardial ischemia) was significantly higher in the LGE-positive group than in the LGE-negative group [12 (70.6%) vs 7 (33.3%); p = 0.02]. Multivariable logistic regression analysis showed that a post-ACh LER < 0% was a significant predictor of LGE positivity (odds ratio 7.75; 95% confidence interval 1.37-43.68; p = 0.02). In conclusion, ACh-provoked coronary vasomotor abnormality is associated with myocardial fibrosis in patients with DCM. These results suggest that coronary endothelial dysfunction is involved in myocardial fibrosis and worsening heart failure concomitant with DCM.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Promotion of Corneal Epithelial Wound Healing in Diabetic Rats by the Fibronectin-Derived Peptide PHSRN.

PURPOSE: Topical application of the fibronectin-derived peptide PHSRN facilitates corneal epithelial wound healing in healthy animals and in patients with nonhealing epithelial defects. We have now examined the effect of PHSRN eye drops on the healing of corneal epithelial wounds in diabetic rats. METHODS: Wistar rats were injected intraperitoneally with streptozotocin to induce diabetes or with a vehicle as a control. Four weeks after confirmation of the corresponding presence or absence of glycosuria, a 3-mm-diameter portion of the corneal epithelium of the right eye was excised and eye drops containing PHSRN (200 µM) or phosphate-buffered saline (PBS) vehicle were administered to the injured eye every 6 hours. RESULTS: The area of the epithelial defect did not differ significantly among the 4 experimental groups (diabetic or nondiabetic rats treated with PHSRN or vehicle) at 12 hours after wounding. At 18 hours, however, the area of the defect in diabetic rats treated with PHSRN (0.50 ± 0.34 mm) was significantly (P < 0.05) smaller than that in diabetic rats treated with PBS (1.06 ± 0.42 mm) and was similar to that in nondiabetic rats treated with PBS (0.60 ± 0.23 mm). The decrease in the size of the epithelial defect in diabetic rats treated with PHSRN was also found to be dependent on the dose of the peptide. CONCLUSIONS: Administration of PHSRN significantly facilitated healing of corneal epithelial wounds in diabetic rats, which suggests that PHSRN eye drops warrant further investigation as a treatment option for patients with diabetic keratopathy.