Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD)

Rationale

Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking.

Objectives

The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model.

Methods

Four groups of male rats (N?=?14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP.

Results

Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only.

Conclusions

Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.     

Wnt1 inducible signaling pathway protein-3 regulation and microsatellite structure in arthritis

OBJECTIVE: Rheumatoid arthritis (RA) synovial tissue expresses several embryonic gene families, including wingless (wnt) and their receptors, frizzled (fz). The Wnt proteins, including Wnt-1, activate the Wnt inducible signaling pathway proteins (WISP), which are members of the CCN family that regulate cell growth and differentiation. WISP3 is of particular interest because it contains a microsatellite region in its coding region that is susceptible to frameshift mutations and leads to a truncated protein. To investigate the contribution of WISP3 to synovial inflammation, we evaluated its expression and regulation in arthritis. METHODS: mRNA and protein expression of WISP3 were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. For mutation analysis, PCR product amplified from genomic DNA of synovial tissue and cultured fibroblast-like synoviocytes (FLS) was subcloned and sequenced. RESULTS: WISP3 mRNA is expressed in synovial tissue, but is 11-fold higher in RA than osteoarthritis (OA) or normal samples. Surprisingly, WISP3 protein levels are similar in RA, OA, and normal synovium samples. Immunohistochemistry of synovial tissue reveals that WISP3 protein is located primarily in the synovial intimal lining. WISP3 mRNA expression is also 6-fold higher in RA FLS compared with OA FLS and 50-fold higher in RA than in normal FLS. When RA FLS are stimulated with interleukin 1 or tumor necrosis factor-a, WISP3 mRNA is significantly increased. The cytokines also increase WISP3 mRNA in OA FLS, but the maximal level in stimulated OA FLS is still less than medium-treated RA FLS. Mutation analysis in the coding region microsatellite of the WISP3 gene in RA and OA synovium and FLS shows a limited number of insertion and deletion mutations. CONCLUSION: WISP3 gene expression is higher in RA synovium and FLS compared with OA and normal synovial tissue and is further induced by proinflammatory cytokines in vitro. Protein levels are not increased, indicating discoordinate regulation of WISP3 protein and mRNA. Although functionally relevant mutations were observed in genomic DNA, they were noted in both OA and RA samples.     

Does Magnifying Narrow-Band Imaging or Magnifying Chromoendoscopy Help Experienced Endoscopists Assess Invasion Depth of Large Sessile and Flat Polyps?

Background

Distinguishing deep submucosa (SM) from superficial SM cancer in large sessile and flat colorectal polyps (>2 cm) is crucial in making the most appropriate therapeutic decision. We evaluated the additional role of magnifying narrow-band imaging (NBI) and magnifying chromoendoscopy (MCE) in assessing the depth of invasion in large sessile and flat polyps in comparison to morphological evaluation performed by experienced endoscopists.

Methods

From May 2011 to December 2011, a total of 85 large sessile and flat polyps were analyzed. Endoscopic features of the polyps were independently evaluated by experienced endoscopists. Subsequently, the polyps were observed using magnifying NBI and MCE.

Results

A total of 58 intramucosal lesions and 27 SM cancers (five superficial and 22 deep) were identified. The diagnostic accuracy of the experienced endoscopists, NBI, and MCE were 92.9, 90.6, and 89.4 %, respectively, for deep SM cancer. In combination with NBI or MCE, the diagnostic accuracy of the experienced endoscopists did not change significantly for deep SM cancer, with an accuracy of 95.3 % for both NBI and MCE.

Conclusions

Conventional colonoscopy can differentiate superficial from deep SM cancers with an accuracy of as high as 92.9 % in large sessile and flat polyps. Further diagnostic strategies are required in order to precisely assess the depth of invasion, especially in large colorectal polyps.     

Effect of Follow-Up Endoscopy on the Outcomes of Patients with Inflammatory Bowel Disease

Background

Little is known about the role of follow-up endoscopy in patients with inflammatory bowel disease (IBD).

Aim

The present study aimed to evaluate whether repeated endoscopies would be beneficial in improving outcomes of patients with IBD.

Methods

Patients who had been initially confirmed to have IBD at two tertiary hospitals in Korea were regularly followed and included in this study. The clinical impact as assessed by the presence or absence of a change in management after endoscopy and cumulative hospitalization rate was compared between two groups classified according to the presence or absence of indications.

Results

A total of 188 patients with IBD were enrolled [69 patients with Crohn’s disease (CD) and 119 with ulcerative colitis (UC)]. Of these patients, 130 underwent follow-up endoscopy (48 with CD and 82 with UC). The rate of management change was significantly higher in the group with indications for follow-up endoscopy (p = 0.001 in CD and <0.001 in UC). The presence of any indications for follow-up endoscopy was found to be a significant predictor of hospitalization risk in patients with UC (p = 0.015), but not in those with CD. However, there was no significant difference in cumulative hospitalization hazard with respect to treatment change in patients without any endoscopic indications (p = 0.561 in CD and 0.423 in UC).

Conclusions

Follow-up endoscopy might not have a significant impact on the overall clinical course and outcomes in patients with IBD. However, the presence of endoscopic indications predicts a poor clinical outcome in UC.     

Primary alveolar soft part sarcoma arising from the cerebellopontine angle

Introduction

Alveolar soft part sarcoma (ASPS), a rare soft tissue malignant neoplasm, frequently metastasizes to the brain. However, primary intracranial ASPS is extremely rare. We present a case of primary intracranial ASPS arising from the cerebellopontine angle (CPA) without demonstrable systemic lesions.

Case report

An 11-year-old girl presented with a recurrent tumor in the right CPA after a partial resection and radiation therapy (RT). Near-total resection with a minimal tumor left in the jugular foramen was performed. The pathological diagnosis was ASPS. There was no evidence of primary extracranial tumors. She underwent adjuvant chemotherapy and gamma knife surgery. At 29 months after the second surgery, magnetic resonance imaging revealed multifocal enhancing lesions at the prepontine cistern, right CPA and medulla oblongata, despite intensive treatment. However, extracranial metastasis was not noted. This case suggested a poor outcome of primary intracranial ASPS, similar to extracranial ASPS.     

The role of M2-2 PDZ-binding motifs in pulmonary innate immune responses to human metapneumovirus

Human metapneumovirus (HMPV) is a leading cause of lower respiratory tract infection (LRTI) in pediatric and geriatric populations. We recently found that two PDZ-binding motifs of the M2-2 protein, 29-DEMI-32 and 39-KEALSDGI-46, play a significant role in mediating HMPV immune evasion in airway epithelial cells (AECs). However, their role in the overall pulmonary responses to HMPV infection has not been investigated. In this study, we found that two recombinant HMPVs (rHMPV) lacking the individual M2-2 PDZ-binding motif are attenuated in mouse lungs. Mice infected with mutants produce more cytokines/chemokines in bronchoalveolar lavage (BAL) fluid compared to mice infected with wild-type rHMPV. In addition, both mutants are able to enhance the pulmonary recruitment of dendritic cells (DCs) and T cells and induce effective protections against the HMPV challenge. The DC maturation is also significantly improved by the motif mutation. Taken together, our data provide proof-of-principle for two live-attenuated M2-2 mutants to be promising HMPV vaccine candidates that are effective in inducing higher pulmonary innate immunity and generating protection against HMPV infection.     

The Ability of Stroke Volume Variation Measured by a Noninvasive Cardiac Output Monitor to Predict Fluid Responsiveness in Mechanically Ventilated Children

Continuous noninvasive cardiac output monitoring (NICOM) is a clinically useful tool in the pediatric setting. This study compared the ability of stroke volume variation (SVV) measured by NICOM with that of respiratory variations in the velocity of aortic blood flow (△Vpeak) and central venous pressure (CVP) to predict of fluid responsiveness in mechanically ventilated children after ventricular septal defect repair. The study investigated 26 mechanically ventilated children after the completion of surgery. At 30 min after their arrival in an intensive care unit, a colloid solution of 10 ml/kg was administrated for volume expansion. Hemodynamic variables, including CVP, stroke volume, and △Vpeak in addition to cardiac output and SVV in NICOM were measured before and 10 min after volume expansion. The patients with a stroke volume increase of more than 15 % after volume expansion were defined as responders. The 26 patients in the study consisted of 13 responders and 13 nonresponders. Before volume expansion, △Vpeak and SVV were higher in the responders (both p values <0.001). The areas under the receiver operating characteristic curves of △Vpeak, SVV, and CVP were respectively 0.956 (95 % CI 0.885–1.00), 0.888 (95 % CI 0.764–1.00), and 0.331 (95 % CI 0.123–0.540). This study showed that SVV by NICOM and △Vpeak by echocardiography, but not CVP, reliably predicted fluid responsiveness during mechanical ventilation after ventricular septal defect repair in children.