Immunohistochemical localization of somatostatin receptor sst2A in human rheumatoid synovium

OBJECTIVE: To identify the somatostatin receptor-expressing cells in rheumatoid synovium using a recently developed antiserum directed against the somatostatin receptor subtype 2A (sst2A). METHODS: We carried out immunohistochemical studies of synovial biopsies from 7 patients with rheumatoid arthritis (RA) and one non-RA patient, using a rabbit polyclonal antiserum directed against sst2A and monoclonal antibodies directed against phenotypic markers. RESULTS: SSt2A was expressed by the endothelial cells of the synovial venules but also by a subset of synovial macrophages. CONCLUSION: The identification of somatostatin receptors on macrophages, which are thought to be important effector cells in RA, may offer mechanistic insights into the potential therapeutic effect of somatostatin (analogs) in RA.     

Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat

Inhibition of mitochondrial complex I is one of the leading hypotheses for dopaminergic neuron death associated with Parkinson's disease (PD). To test this hypothesis genetically, we used a mouse strain lacking functional Ndufs4, a gene encoding a subunit required for complete assembly and function of complex I. Deletion of the Ndufs4 gene abolished complex I activity in midbrain mesencephalic neurons cultured from embryonic day (E) 14 mice, but did not affect the survival of dopaminergic neurons in culture. Although dopaminergic neurons were more sensitive than other neurons in these cultures to cell death induced by rotenone, MPP⁺, or paraquat treatments, the absence of complex I activity did not protect the dopaminergic neurons, as would be expected if these compounds act by inhibiting complex 1. In fact, the dopaminergic neurons were more sensitive to rotenone. These data suggest that dopaminergic neuron death induced by treatment with rotenone, MPP⁺, or paraquat is independent of complex I inhibition.     

Clinically Useful Diagnostic Tool of Contrast Enhanced Ultrasonography for Focal Liver Masses: Comparison to Computed Tomography and Magnetic Resonance Imaging

Background/Aims

To evaluate the diagnostic value of contrast (SonoVue®) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses.

Methods

CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI.

Results

The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765.

Conclusions

If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.     

Salience network integrity predicts default mode network function after traumatic brain injury

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)--which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae--regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control.     

Plasma Levels of IL-23 and IL-17 before and after Antidepressant Treatment in Patients with Major Depressive Disorder

Objective

Cytokines are believed to have a role in the pathophysiology of major depression. The alteration in levels of pro-inflammatory cytokines [interleukin 1β (IL-1β), IL-2, IL-6, IL-12, interferon γ, and tumor necrosis factor α] in major depression supports the cytokine hypothesis of this illness. IL-23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on their role in major depression. This study investigated the potential role of the IL-23 and IL-17 axis in major depression.

Methods

Plasma IL-23 and IL-17 levels were measured in 26 major depressive disorder (MDD) patients before and after 6-week treatment with antidepressants; these levels were measured in 28 age- and sex-matched normal controls. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated using quantitative enzyme-linked immunosorbent assay.

Results

Pre-treatment plasma levels of IL-23 and IL-17 in MDD patients were not significantly different from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6 weeks of antidepressant treatment were not different from the baseline levels. There was no significant correlation between changes in the cytokine levels and changes in the HDRS scores representing the severity of depression.

Conclusion

The present study does not support a potential involvement of IL-23 and IL-17 axis in major depression. Replication and extension using a larger sample are required.     

Immunohistochemical Localization and Distribution of Proliferating Cell Nuclear Antigen in the Rabbit Mandibular Condyle Following Experimental Induction of Anterior Disk Displacement

The purpose of the present study was to identify proliferating cells in control versus experimental condyles two weeks following experimental Induction of anterior disk displacement (ADD) in the rabbit craniomandibular joint (CMJ). The right joint of 15 rabbits was exposed surgically and all diskal attachments were severed except for the posterior attachment. The disk was then repositioned anteriorly and sutured to the zygomatic arch. The left joint served as a sham-operated control. Ten additional joints were used as nonoperated controls. Mandibular condyles were excised two weeks following surgery and processed for proliferating cell nuclear antigen (PCNA) immunostaining. In control and sham operated condyles, PCNA was localized in the nuclei of chondroblasts of the reserve cell layer, chondrocytes of the upper hypertrophic layer and bone marrow cells of the subchondral bone. In contrast to control joints, the PCNA positive cells of the experimental joints were located throughout the osteoarthritic condylar cartilage. In addition, the percentage of PCNA positive cells of the osteoarthritic condylar cartilage was statistically significantly higher when compared to the control group, p < 0.05. It was concluded that surgical induction of ADD in the rabbit CMJ leads to an increase in mitosis of chondrocytes, which lead to cell proliferation and subsequent hyperplasia of the condylar cartilage.     

Challenges to Research and Innovation to Optimize Deceased Donor Organ Quality and Quantity

Solid organ transplantation is encumbered by an increasing number of waitlisted patients unrequited by the current organ supply. Preclinical models suggest that advances in deceased donor management and treatment can increase the quantity and quality of organs available for transplantation. However, the science of donor intervention and the execution of high quality, prospective, multi‐center, randomized‐controlled trials are restricted by a myriad of logistical challenges mired in regulatory and ethical ambiguity. By highlighting the obstacles to conducting research in deceased donors, this report endeavors to stimulate the creation of a multi‐disciplinary framework to facilitate the design, implementation and supervision of innovative trials that increase the quantity and/or quality of deceased donor organs.     

Etomidate dose-response on somatosensory and transcranial magnetic induced spinal motor evoked potentials in primates

Abstract

There is growing interest and need to monitor reliably both motor (MEP) and somatosensory (SEP) evoked potentials under anesthesia. On a pre-established primate model, the present study examined the effect of incremental etomidate (ET) dosages on spinal neural MEPs to transcranial magnetic stimulation (TMS) and posterior tibial rate (PTN) SEPs. Through a small thoracic Tl 1-T12 laminotomy, an insulated double bipolar electrode was inserted epidurally in seven cynomolgus monkeys. Spinal TMS-MEPs, PTN-SEPs, and frontal EEC were tested against graded increase of ET doses. Etomidate 0.5 mg kg-1 i.v. was initially given and followed by 30 min continuous infusion of 0.01 mg kg^1 min~1, 0.018, 0.032, 0.056, 0.1, and 0.18 mg kg'1 min"1 in that order. Measurable spinal MEPs and SEPs were recorded under deep ET anesthesia (total 12.38 mg kg-1 cumulative dose over 180 min). The EEC showed marked slow wave and graded burst suppression at cumulative dose of ^3.14 mg kg~'. The direct (D) and subsequent initial indirect (I) waves (Ij, l2,13) were reproducible at doses <0.18 mg kg~7 min~1 infusion. The latter l-waves (l4 and l5) showed graded loss at infusion dosage 0.056 mg kg'1 min~1. Etomidate remains an anesthetic of attractive features in neuroanesthesia. In the primate model, neural MEPs-SEPs were reproducible despite the exceedingly high dose of ET and markedly depressed EEC. Moreover, MEP-SEP can be monitored during ET burst-suppressive neuroprotective state. The study may set a model in humans for intra-operative multi-modality neurophysiologic recording under ET-based anesthesia. [Neurol Res 1999; 21: 714-7201