Concurrent benzodiazepine use in older adults treated with antidepressants in Asia.

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates. METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed. RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Alterations of CSF cystatin C levels and their correlations with CSF Αß40 and Αß42 levels in patients with Alzheimer's disease, dementia with lewy bodies and the atrophic form of general paresis.

Immunohistochemical studies have revealed that cystatin C (CysC) co-localizes with amyloid-ß (Αß) in amyloid-laden vascular walls and in the senile plaque cores of amyloid. In vitro and in vivo animal studies suggest that CysC protects against neurodegeneration by inhibition of cysteine proteases, inhibition of Αß aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aß levels in various types of dementia with characteristic amyloid deposits, such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and the atrophic form of general paresis (AF-GP). We assessed the serum and CSF levels of CysC and the CSF levels of Aß40 and Aß42 in patients with AD (n = 51), DLB (n = 26) and AF-GP (n = 43) and normal controls (n = 30). Using these samples, we explored the correlation between CSF CysC and CSF Aß levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aß42 levels were significantly lower in all three dementia groups (all p<0.001); serum CysC levels were the same in the AD and DLB groups, and were lower in the AF-GP group (p = 0.008). The CSF CysC levels were positively correlated with both the CSF Aß40 and Aß42 levels in the AD, AF-GP and normal control groups (r = 0.306∼0.657, all p<0.05). Lower CSF CysC levels might be a common feature in dementia with characteristic amyloid deposits. Our results provide evidence for the potential role of CysC involvement in Aß metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.

In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation.

OBJECTIVE: To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI. MATERIALS AND METHODS: 1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5×10(5) MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals. RESULTS: Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration. CONCLUSION: MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves.

Peripheral nerve repair: monitoring by using gadofluorine M-enhanced MR imaging with chitosan nerve conduits with cultured mesenchymal stem cells in rat model of neurotmesis.

PURPOSE: To observe the longitudinal changes of nerve repair in rats after tissue-engineered construct implantation at magnetic resonance (MR) imaging and to determine whether the enhanced nerve regeneration with use of tissue-engineered constructs could be monitored with gadofluorine M-enhanced MR imaging or nerve T2 relaxation time measurement. MATERIALS AND METHODS: All experimental protocols were approved by the institutional Animal Use and Care Committee. Tissue-engineered constructs were prepared by seeding mesenchymal stem cells (MSCs) into chitosan nerve tubes. Thirty-six rats with sciatic nerve transection injury underwent nerve tube implantation with (n = 18) or without (n = 18) MSC seeding. Sequential T2 measurement, gadofluorine M-enhanced MR imaging, and sciatic function index measurement were performed over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and signal intensity at gadofluorine M-enhanced T1-weighted imaging were measured and were compared by using repeated-measures analysis of variance followed by the Student-Neuman-Keuls post-hoc test for multiple pairwise comparisons. RESULTS: Nerve T2 relaxation times and gadofluorine M enhancement, as well as functional changes, showed a similar time course. Nerves implanted with MSC-seeded tubes achieved slightly better functional recovery and enhanced nerve regeneration while showing a slower return to baseline T2 relaxation time and a more rapid decline in gadofluorine M enhancement compared with nerves implanted with chitosan tubes alone. T2 values of the distal portion of transected nerves showed a more rapid return to baseline level than did gadofluorine M enhancement. CONCLUSION: Peripheral nerve repair with use of tissue-engineered constructs can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting nerve regeneration.

Transplanted neural stem cells promote nerve regeneration in acute peripheral nerve traction injury: assessment using MRI.

OBJECTIVE: The purpose of our study was to monitor neural stem cells (NSCs) transplanted in acute peripheral nerve traction injury and to use MRI to assess the ability of NSCs to promote nerve regeneration. MATERIALS AND METHODS: After labeling with gadolinium-diethylene triamine pentaacetic acid (gadopentetate dimeglumine) and fluorescent dye (PKH26), 5 × 10(5) NSCs were grafted to acutely distracted sciatic nerves in 21 New Zealand White rabbits. In addition, 5 × 10(5) unlabeled NSCs (n = 21) and vehicle alone (n = 21) subjects were injected as a control. Serial MRI was performed with a 1.5-T scanner to determine the distribution of grafted cells. Sequential T1 and T2 values of the nerves and functional recovery were measured over a 70-day follow-up period, with histologic assessments performed at regular intervals. RESULTS: The distribution and migration of labeled NSCs could be tracked with MRI until 10 days after transplantation. Compared with vehicle control, nerves grafted with labeled or unlabeled NSCs had better functional recovery and showed improved nerve regeneration but exhibited a sustained increase of T1 and T2 values during the phase of regeneration. CONCLUSION: Gadopentetate dimeglumine-based labeling allowed short-term in vivo MRI tracking of NSCs grafted in injured nerves. NSCs transplantation could promote nerve regeneration in acute peripheral nerve traction injury as shown by a prolonged increase of nerve T1 and T2 values.

Intraspinal primitive neuroectodermal tumor: imaging findings in six cases.

PURPOSE: To retrospectively review CT and MRI findings in a series of six intraspinal primitive neuroectoderal tumors and to find out their radiological features. METHODS: CT and MRI of six patients with surgically and pathologically proved intraspinal primitive neuroectoderal tumor were retrospectively reviewed. The tumor location, morphological features, signal intensity, calcification, contrast enhancement characteristics, involvement of paraspinal soft tissues and adjacent bony structures were assessed. RESULTS: Of six patients, four had extradural lesions and two had intradural, extramedullary lesions. Most lesions were well defined and manifested heterogeneous iso- or hypo-intense signal on T1-weighted imaging and hyper-intense signal on T2-weighted imaging and moderate attenuation on CT, and were heterogeneously enhanced after contrast enhancement. The lesion extending through the intervertebral foramen with a large paraspinal soft tissue mass formed was found in four patients and vertebral bone involvement was seen in four patients. CONCLUSIONS: Although imaging findings are not specific of intraspinal primitive neuroectoderal tumor, this diagnosis could be suggested when MR imaging depicts an intradural, extramedullary or extradural large well-circumscribed mass which extends out from intervertebral foramen and invades paraspinal soft tissues or vertebral bones in a young patient.

In vivo MR imaging tracking of transplanted mesenchymal stem cells in a rabbit model of acute peripheral nerve traction injury.

PURPOSE: To investigate in vivo MRI tracking mesenchymal stem cells (MSCs) in peripheral nerve injures using a clinically available paramagnetic contrast agent (Gd-DTPA) and commercially available rhodamine-incorporated transfection reagents (PEI-FluoR). MATERIALS AND METHODS: After bone marrow MSCs were labeled with Gd-DTPA and PEI-FluoR complex, the labeling efficacy and longevity of Gd-DTPA maintenance were measured and cell viability, proliferation, and apoptosis were assessed. Thirty-six rabbits with acute sciatic nerve traction injury randomly received 1 × 10(6) labeled (n = 12) or unlabeled MSCs (n = 12) or vehicle alone injection. The distribution and migration of implanted cells was followed by MRI and correlated with histology. The relative signal intensity (RSL) of the grafts was measured. RESULTS: The labeling efficiency was 76 ± 4.7% and the labeling procedure did not influence cell viability, proliferation, and apoptosis. A persistent higher RSL in grafts was found in the labeled group compared with the unlabeled and vehicle groups until 10 days after transplantation (P < 0.05). The distribution and migration of labeled cells could be tracked by MRI until 10 days after transplantation. Transplanted MSCs were not found to transdifferentiate into Schwann-like cells within 14-day follow-up. CONCLUSION: Labeling MSCs with the dual agents may enable cellular MRI of the engraftment in the experimental peripheral nerve injury.

Magnetic resonance imaging of mesenchymal stem cells labeled with dual (MR and fluorescence) agents in rat spinal cord injury.

RATIONALE AND OBJECTIVES: In vivo tracking cells using gadolinium-based contrast agents have the important advantage of providing a positive contrast on T1-weighted images, which is less likely to be confused with artifacts because of postoperative local signal voids such as metal, hemorrhage, or air. The aim of this study is to paramagnetically and fluorescently label marrow with dual agents (gadolinium-diethylene triamine penta-acetic acid [Gd-DTPA] and PEI-FluoR) and track them after transplantation into spinal cord injury (SCI) with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Marrow mesenchymal stem cells (MSCs) from Sprague-Dawley rats were incubated with PEI-FluoR (rhodamine-conjugated PEI-FluoR) and Gd-DTPA complex for labeling. After labeling, cellular viability, proliferation, and apoptosis were evaluated. T1 value and longevity of intracellular Gd-DTPA retention were measured on a 1.5 T MRI scanner. Thirty-six SCI rats were implanted with labeled and unlabeled MSCs and phosphate-buffered saline. Then, serial MRI and Basso-Beattie-Bresnehan (BBB) locomotor tests were performed and correlated with fluorescent microscopy. The relative signal intensity (RSL) of the engraftment in relation to normal cord was measured and the linear mixed model followed by post-hoc Bonferroni test was used to identify significant differences in RSL as well as BBB score. RESULTS: MSCs could be paramagnetically and fluorescently labeled by the dual agents. The labeling did not influence the cellular viability, proliferation, and apoptosis. The longevity of Gd-DTPA retention in labeled MSCs was up to 21 days. The distribution and migration of labeled MSCs in SCI lesions could be tracked until 7 days after implantation on MRI. The relative signal intensities of SCI rats treated with labeled cells at 1 day and 3 days (1.34 +/- 0.02, 1.27 +/- 0.03) were significantly higher than rats treated with unlabeled cells (0.94 +/- 0.01, 0.99 +/- 0.02) and phosphate-buffered saline (0.91 +/- 0.01, 0.95 +/- 0.01) (P < .05). Rats treated with labeled MSCs or unlabeled MSCs achieved significantly higher BBB scores than controls at 14, 21, 28, and 35 days after injury (P < .05). CONCLUSIONS: Labeling MSCs with the dual agents may enable cellular MRI and tracking in experimental spinal cord injury.