<ORIGINAL ARTICLE>Localization of anti-monocyte/macrophage antibody-positive cells in periodontal tissue of rat maxillary molars after orthodontic tooth movement

To examine the localization of monoclonal anti-monocyte/macrophage (ED1) and macrophage (ED2) antibody-positive cells in periodontium, rat maxillary molar teeth were moved by insertion of band materials. The orthodontic tooth movement was elicited for 5 days, and paraffin-embedded maxillary teeth were stained by fluorescent immunocytochemistry and observed using a confocal laser scanning microscope. The localization of ED1-positive mononuclear cells in the experimental teeth was little different from that in the controls. While ED2-positive mononuclear cells were located throughout the periodontium on the distalside of controls, the number of positive cells decreased on the pressure side of the treated teeth. The present study suggested that most of the immunoreactive mononuclear cells on the distal side of controls are macrophages, while the positive cells on the pressure side of the experimental teeth are osteoclast precursors and a small number of macrophages

Age-Specific Effectiveness and Safety of Newly Initiated Insulin Therapy in Japanese Patients with Uncontrolled Diabetes

INTRODUCTION: One consequence of population aging is an increase in the number of elderly patients with diabetes mellitus. These elderly patients often experience atherosclerotic complications, and diabetes prevention and management are strongly desired to promote health and reduce the financial burden on the healthcare system. In this study, we conducted an age-specific evaluation of the effectiveness and safety of comprehensive management with newly initiated insulin therapy over a 1-year period in elderly (≥65 years) compared with non-elderly (≤64 years) Japanese patients with uncontrolled diabetes [glycated hemoglobin (HbA1c) ≥ 8% for ≥ 3 months]. METHODS: This retrospective single-center cohort study was conducted in Japan. We screened all outpatients with diabetes mellitus who visited the clinic for diabetes treatment between December 2006 and March 2011. Of these patients, 132 with type 2 diabetes who were newly initiated on insulin therapy for continued poor glycemic control and undergoing comprehensive management through self-monitoring of blood glucose (SMBG) were registered to the study. RESULTS: Thirty-two of 132 registered patients were excluded from the analysis. Among the 100 patients (67 non-elderly, 33 elderly) included in the analysis, median age and proportion of male patients was 69 years and 66.7%, respectively, among the elderly, and 52 years and 68.7%, respectively, among the non-elderly patients. After initiation of insulin therapy, median HbA1c levels improved from 9.6% to 7.2% in elderly patients, and from 10.8% to 7.3% in non-elderly patients at baseline and 12 months. Severe hypoglycemic events were not observed in either patient group; however, uncontrolled diabetes was ongoing in 31.8% of non-elderly and 15.4% of elderly patients, and obesity was associated with poor glycemic control. CONCLUSION: Our results indicate that the effectiveness and safety of newly initiated insulin therapy are similar between elderly and non-elderly Japanese patients with uncontrolled diabetes, and highlight the importance of comprehensive management using SMBG to avoid hypoglycemia. Better glycemic control supported by adequate intensive management is required to improve mortality and morbidity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13300-013-0049-4) contains supplementary material, which is available to authorized users

Neuromolecular basis of faded perception associated with unreality experience

Perceptual changes in shape, size, or color are observed in patients with derealization symptoms; however, the underlying neural and molecular mechanisms are not well understood. The current study explored the relationship between neural activity associated with altered colorfulness perception assessed by fMRI and striatal dopamine D₂ receptor availability measured by [¹¹C]raclopride PET in healthy participants. Inside an fMRI scanner, participants performed the saturation adaptation task, where they rated how much vivid/faded visual objects looked like real/unreal ones using a visual analog scale. We found that participants experienced greater unreality when they perceived fadedness than vividness despite physically identical saturation. The combined fMRI and PET analyses revealed that the faded perception-related activities of the dorsolateral prefrontal and parietal cortex were positively correlated with striatal D₂ receptor availability. This finding may help to understand the neuromolecular mechanisms of faded perception associated with feeling unreal in derealization symptoms

Histamine H₃ receptor density is negatively correlated with neural activity related to working memory in humans

Background: The histamine H₃ receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H₃ receptor are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H₃ receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H₃ receptors in the prefrontal cortex.Findings: Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H₃ receptor density was measured with the selective PET radioligand [¹¹C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H₃ receptors in this region.Conclusions: Higher neural activity of working memory was associated with lower H₃ receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H₃ receptor in working memory and indicates the potential of H₃ receptor as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders

Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans

BackgroundThe histamine H3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H3 receptors in the prefrontal cortex.FindingsTen healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H3 receptor density was measured with the selective PET radioligand [11C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H3 receptors in this region.ConclusionsHigher neural activity of working memory was associated with lower H3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H3 receptors in working memory and indicates the potential of H3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders

Neuromolecular basis of faded perception associated with unreality experience.

Perceptual changes in shape, size, or color are observed in patients with derealization symptoms; however, the underlying neural and molecular mechanisms are not well understood. The current study explored the relationship between neural activity associated with altered colorfulness perception assessed by fMRI and striatal dopamine D receptor availability measured by [C]raclopride PET in healthy participants. Inside an fMRI scanner, participants performed the saturation adaptation task, where they rated how much vivid/faded visual objects looked like real/unreal ones using a visual analog scale. We found that participants experienced greater unreality when they perceived fadedness than vividness despite physically identical saturation. The combined fMRI and PET analyses revealed that the faded perception-related activities of the dorsolateral prefrontal and parietal cortex were positively correlated with striatal D receptor availability. This finding may help to understand the neuromolecular mechanisms of faded perception associated with feeling unreal in derealization symptoms

Brain 5-HT2A receptor binding and its neural network related to behavioral inhibition system

Rationale The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. Objectives To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Results Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Conclusions Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion