Changes of motor cortical excitability and response inhibition in patients with obsessive­compulsive disorder

Background: Deficits in cortical inhibitory processes have been suggested as underlying pathophysiological mechanisms of obsessive­compulsive disorder (OCD). We examined whether patients with OCD have altered cortical excitability using paired-pulse transcranial magnetic stimulation (TMS). We also tested associations between TMS indices and OCD-related characteristics, including age of onset and response inhibition in the go/no-go paradigm, to examine whether altered cortical excitability contributes to symptom formation and behavioural inhibition deficit in patients with OCD. Methods: We assessed motor cortex excitability using paired-pulse TMS in 51 patients with OCD and 39 age-matched healthy controls. We also assessed clinical symptoms and response inhibition in the go/nogo task. All patients were undergoing treatment with serotonin reuptake inhibitors. We performed repeated-measures multivariate analysis of covariance to compare TMS indices between patients with OCD and controls. Results: Compared to controls, patients with OCD showed a shorter cortical silent period and decreased intracortical facilitation. However, we found no significant difference between groups for resting motor threshold or short-interval intracortical inhibition. In the OCD group, the shortened cortical silent period was associated with a prompt reaction time in the go/no-go task and with early onset of OCD. Limitations: We could not exclude the influence of medications on motor cortex excitability. Conclusion: These findings suggest abnormal cortical excitability in patients with OCD. The associations between cortical silent period and response inhibition and age of onset further indicate that altered cortical excitability may play an important role in the development of OCD.

Human umbilical cord blood-derived CD34-positive endothelial progenitor cells stimulate osteoblastic differentiation of cultured human periosteal-derived osteoblasts.

The aim of this study was to examine the effects of human umbilical cord blood-derived CD34-positive endothelial progenitor cells (CD34+ EPCs) on osteoblastic differentiation of cultured human periosteal-derived osteoblasts (POs). CD34+ cells from human umbilical cord blood were sorted to purify more EPCs in characterization. These sorted cells showed CD31, VE-cadherin, and KDR expression as well as CD34 expression and formed typical tubes in Matrigel. These sorted cells were referred to as human cord blood-derived CD34+ EPCs. In in vivo bone formation using a miniature pig model, the newly formed bone was clearly examined in defects filled with polydioxanone/pluronic F127 (PDO/Pluronic F127) scaffolds containing either human umbilical cord blood-derived CD34+ EPCs and POs or human umbilical vein endothelial cells (HUVEC) and POs; however, the new bone had the greatest density in the defect treated with CD34+ EPCs and POs. Osteoblastic phenotypes of cultured human POs using ALP activity and von Kossa staining were also more clearly found in CD34+ EPC-conditioned medium than CD34-negative (CD34-) cell-conditioned medium, whereas HUVEC-conditioned medium had an intermediate effect. PCR array for common cytokines and growth factors showed that the secretion of interleukin (IL)-1ß was significantly higher in CD34+ EPCs than in HUVEC, followed by level in CD34- cells. In addition, IL-1ß also potently and dose dependently increased ALP activity and mineralization of POs in culture. These results suggest that human umbilical cord blood-derived CD34+ EPCs stimulates osteoblastic differentiation of cultured human POs. The functional role of human umbilical cord blood-derived CD34+ EPCs in increasing the osteogenic phenotypes of cultured human POs may depend on IL-1ß secreted from human umbilical cord blood-derived CD34+ EPCs.

Hybridization of the natural antibiotic, cinnamic acid, with layered double hydroxides (LDH) as green pesticide.

BACKGROUND, AIM, AND SCOPE: Heavy application of highly toxic synthetic pesticides has been committed to protect crops against insects and diseases, which have brought about serious environmental problems. Thus, an inevitable and fundamental issue has been how to protect crops without harmful effects on nature. As a fascinating nature-compatible approach, we have attempted to hybridize soil-compatible layered double hydroxides (LDHs) with natural antibiotic substances. Only a few of natural antibiotic substances are available for pest control mainly because of their inherent properties such as easy degradability, high minimum inhibition concentration for practical application, and often extremely low availability, whereas LDHs exhibit unique properties such as anion exchange capacity, acid lability, and high affinity to ubiquitous carbonate ion which make them an excellent inorganic matrix to carry labile biomolecules in soils. This study focuses on the behavior of cinnamate-LDH hybrid in soils and the evaluation of its potentials as a green pesticide. MATERIALS AND METHODS: The cinnamate-LDH hybrid was synthesized by a typical coprecipitation method. Cinnamic acid was analyzed by high performance liquid chromatography which was operated at 280 nm with C18 column. Its controlled release property was evaluated in a cultivated soil as well as a simulated soil solution. Its antifungal activity was examined against the growth of Phytophyhora capsici in a potato dextrose agar medium and a red pepper seedling, respectively. RESULTS AND DISCUSSION: Structural characterization by X-ray diffraction, infra-red, and thermal analysis indicates that cinnamate molecules are safely intercalated into the interlayer space of inorganic layers of LDH by the electrostatic interaction to have an empirical formula of Mg(3)Al(OH)(8).CAN . 3.1H(2)O. The overall release pattern of the intercalated cinnamate in the soil solution could be best described by the power-function equation [Formula: see text]. This suggests that diffusion-controlled processes besides simple ion-exchange process play an important role in release of the intercalated cinnamate. Furthermore, its behavior in a cultivated soil clearly shows that hybridization leads to protection of cinnamate against the degradation as well as to a controlled release in soils. Its antifungal activity against the growth of P. capsici in a potato dextrose agar medium and a red pepper seedling definitely shows that the hybrid is very effective in controlling the root rot of red pepper. CONCLUSION: This study demonstrates that the hybridization of natural antibiotic substances with layered double hydroxides could be a fascinating alternative for green formulation of pesticides. This unique hybrid system leads to the salient features such as protection of the substances against chemical and microbial degradations, controlled release, and nature compatibility. RECOMMENDATIONS AND PERSPECTIVES: This study suggests one of the sound strategies to make a breakthrough in the formulation of green pesticides. Hybridization with inorganic matrixes not only enables the natural antibiotic substances to replace the synthetic ingredients but also adjuvants to be excluded from the formulations. Furthermore, the resulting hybrid exhibits a controlled release of the intercalated substances. Although substantiated further, this study is expected to attract a great deal of attention to reliable application of natural antibiotic substances in green protection of crops and agricultural products.

A randomized controlled study of sequentially applied repetitive transcranial magnetic stimulation in obsessive-compulsive disorder.

OBJECTIVE: The present study investigated possible therapeutic effects and safety of sequentially combined low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex and supplementary motor area in patients with treatment-resistant obsessive-compulsive disorder. METHOD: Between February 2007 and January 2008, we carried out a study with a rater-blinded, sham-controlled design in which 20 patients with treatment-resistant obsessive-compulsive disorder, confirmed by a psychiatrist after use of the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version, were randomly assigned to either active rTMS (n = 10) or sham treatment (n = 10). Over 10 days, rTMS of 1 Hz was given at 110% of the motor threshold for 20 minutes over the right dorsolateral prefrontal cortex and sequentially at 1 Hz at 100% of the motor threshold for 20 minutes over the supplementary motor area. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS) score. RESULTS: For the between-group analyses, there were no significant differences over 4 weeks between the active and sham groups on the YBOCS (F = 0.01, P = .92) and the Montgomery-Asberg Depression Rating Scale (MADRS; F = 0.39, P = .54). In repeated-measures analyses on all subjects, there was a significant effect of time on the YBOCS (F = 5.48, P = .009) and the MADRS (F = 6.55, P = .004). There were no significant group-by-time interactions for the YBOCS (F = 0.03, P = .94) or the MADRS (F = 0.09, P = .67). CONCLUSIONS: These findings suggest that 10 sessions of sequential rTMS of the right dorsolateral prefrontal cortex and the supplementary motor area at low frequency had no therapeutic effect on obsessive-compulsive symptoms. However, rTMS was a safe method of treatment, and there was no significant change in cognitive function after rTMS. Further controlled studies using a more sophisticated sham system in larger samples are required to confirm the effect of rTMS in obsessive-compulsive disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00932204.

Reduced P3 amplitudes by negative facial emotional photographs in schizophrenia.

Event-related potentials (ERPs), mostly P3, were measured in 20 schizophrenia and 20 healthy control subjects, in order to determine whether patients with schizophrenia have greater impairment in the processing of negative emotions. Study subjects were instructed to feel and respond to rare targets of facial photographs placed between frequent nontarget checkerboards. We found that P3 amplitudes associated with negative emotional photographs, in normal controls, were significantly larger than those of positive stimuli. Unlike the controls, in patients with schizophrenia, P3 amplitudes generated by negative emotional targets were significantly smaller than those of positive stimuli. We conclude that schizophrenia patients might be neurophysiologically different from healthy controls in terms of the manner in which they process facial emotion. Our findings are in line with previous neurobehavioral studies, in which patients with schizophrenia showed greater impairment in the recognition of negative emotions.