Investigations of rodent urinary bladder carcinogens: collection, processing, and evaluation of urine and bladders

Examination of the urine and the bladder epithelium are essential to the investigation of mechanisms of urinary bladder carcinogens in rodents. However, urine and bladder tissue specimens must be collected and processed properly if accurate data are to be derived. The optimum specimen for analysis of urinary constituents is fresh void urine collected from nonfasting animals. Fasting the animal prior to urine collection changes the normal composition, including pH. Many of the normal urinary constituents can influence the mode of action of bladder carcinogens, especially for non-genotoxic agents. Light microscopy is routinely used to examine the bladder epithelium. However, it is often necessary to use more sensitive techniques, such as scanning electron microscopy (SEM) to detect subtle cytotoxic changes in the superficial cell layer of the urothelium, and bromodeoxyuridine (BrdU) incorporation, PCNA, or Ki-67 immunohistochemistry to determine the labeling index for cell proliferation. The urinary bladder must be handled gently and inflated with fixative in situ before the animal dies to avoid artifactual autolytic damage to the bladder epithelium that is visible by SEM and may be mistaken for treatment-related changes. The purpose of this paper is to provide information for the proper collection and examination of urine and the urinary bladder.     

Muscle activity,cross-sectional area,and density following passive standing and whole body vibration: A case series

Objective

To investigate the effects of intermittent passive standing (PS) and whole body vibration (WBV) on the electromyography (EMG) activity, cross-sectional area, and density of lower extremity muscles in individuals with chronic motor complete spinal cord injury (SCI).

Design

Case series.

Methods

Seven adult men with chronic (≥2 years), thoracic motor complete (AIS A–B) SCI completed a 40-week course of thrice-weekly intermittent PS-WBV therapy, in a flexed knee posture (160°), for 45 minutes per session at a frequency of 45 Hz and 0.6–0.7 mm displacement using the WAVE^® Pro Plate, with an integrated EasyStand™ standing frame. EMG was measured in major lower extremity muscles to represent muscle activity during PS-WBV. The cross-sectional area and density of the calf muscles were measured using peripheral quantitative computed tomography at the widest calf cross-section (66% of the tibia length) at pre- and post-intervention. All measured variables were compared between the pre- and post-intervention measurements to assess change after the PS-WBV intervention.

Results

PS-WBV acutely induced EMG activity in lower extremity muscles of SCI subjects. No significant changes in lower extremity EMG activity, muscle cross-sectional area, or density were observed following the 40-week intervention.

Conclusions

Although acute exposure to PS-WBV can induce electrophysiological activity of lower extremity muscles during PS in men with motor complete SCI, the PS-WBV intervention for 40 weeks was not sufficient to result in enhanced muscle activity, or to increase calf muscle cross-sectional area or density.     

Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice

Mood disorders cause much suffering and are the single greatest cause of lost productivity worldwide. Although multiple medications, along with behavioral therapies, have proven effective for some individuals, millions of people lack an effective therapeutic option. A common serotonin (5-HT) transporter (5-HTT/SERT, SLC6A4) polymorphism is believed to confer lower 5-HTT expression in vivo and elevates risk for multiple mood disorders including anxiety, alcoholism, and major depression. Importantly, this variant is also associated with reduced responsiveness to selective 5-HT reuptake inhibitor antidepressants. We hypothesized that a reduced antidepressant response in individuals with a constitutive reduction in 5-HTT expression could arise because of the compensatory expression of other genes that inactivate 5-HT in the brain. A functionally upregulated alternate transporter for 5-HT may prevent extracellular 5-HT from rising to levels sufficiently high enough to trigger the adaptive neurochemical events necessary for therapeutic benefit. Here we demonstrate that expression of the organic cation transporter type 3 (OCT3, SLC22A3), which also transports 5-HT, is upregulated in the brains of mice with constitutively reduced 5-HTT expression. Moreover, the OCT blocker decynium-22 diminishes 5-HT clearance and exerts antidepressant-like effects in these mice but not in WT animals. OCT3 may be an important transporter mediating serotonergic signaling when 5-HTT expression or function is compromised.     

The role of interferon-γ in cardiovascular disease: an update

Inflammation Research - Cardiovascular disease (CVD) is the leading cause of death, globally, and its prevalence is only expected to rise due to the increasing incidence of co-morbidities such as...     

Effect of Sodium Hypochlorite Concentration on Electronic Apex Locator Reliability

This ex vivo study aimed to measure the performance of an electronic apex locator (EAL) in the presence of sodium hypochlorite irrigants with different concentrations. Two EALs (Root ZX Mini and Locapex 6) were used to locate the apical foramen in 10 extracted single-rooted teeth in the presence of 0.5%, 2.5% and 5% sodium hypochlorite. Visual working lengths were also determined using #10 K-file under a microscope before the electronic measurements were made. The performance of both EALs was compared for the electronic working lengths determined under the different concentrations of sodium hypochlorite. A multiple-way ANOVA and PLSD Fisher’s test with an α risk fixed at 5% were conducted. There were no statistical differences in the working lengths determined by both EALs between the three groups with different concentrations of sodium hypochlorite and their visual control measurements. When a ± 0.5 mm margin was applied, the Root ZX Mini and the Locapex 6 presented 88% and 83% accuracy, respectively. Sodium hypochlorite concentration in irrigants does not affect the accuracy and reliability of either the Root ZX Mini or the Locapex 6. Electronic apex locators are reliable with any concentration of sodium hypochlorite irrigants.     

Large‐scale brain network abnormalities in Huntington's disease revealed by structural covariance

Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel‐based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre‐specified motor, working memory, cognitive flexibility, and social‐affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre‐HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre‐HD were observed, but increased positive correlations were evident for mHD, relative to pre‐HD and HC. These findings could be explained by a HD‐related neuronal loss heterogeneously affecting the examined network at the pre‐HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow‐up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. Hum Brain Mapp 37:67–80, 2016. © 2015 Wiley Periodicals, Inc.     

Patient Satisfaction with Community-Based Psychiatric Services

The aim of this study is to establish the satisfaction of patients with community-based psychiatric services, developed in the context of Italian psychiatric reform. The Verona Services Satisfaction Scale (VSSS-54) was used to measure satisfaction among 229 patients cared for by the Desio Department of Mental Health. Patients were gene rally satisfied (23 percent of the patients were unsatisfied), but in some dimensions (“Information” and “Relatives’ involvement”) they reported a low level of satisfaction. In the regression models, the sociodemographic, diagnostic, and service utilization variables explained only a low percentage of the satisfaction variance. Continuity of care and satisfaction with psychiatric services do not seem to be related; satisfaction does not predict the number of admissions to a psychiatric ward in the year after evaluation. The conclusion of the study is that satisfaction is a useful indicator in monitoring quality of care: by analyzing different dimensions of satisfaction, we can focus professionals on patients’ needs and expectation and modify the services accordingly.