Dual regulation of clock gene Per2 expression in discrete brain areas by the circadian pacemaker and methamphetamine‐induced oscillator in rats

Behavioral rhythms induced by methamphetamine (MAP) treatment in rats are independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). To know the site and mechanism of an underlying oscillation (MAP‐induced oscillator; MAO), extra‐SCN circadian rhythms in the discrete brain areas were examined in rats with and without the SCN. To fix the phase of MAO, MAP was supplied in drinking water at a restricted time of day for 14 days (R‐MAP) and subsequently given ad libitum (ad‐MAP). Plain water was given to the controls at the same restricted time (R‐Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN‐intact rats, MAO was induced by R‐MAP and behavioral rhythms were phase‐delayed from the restricted time under ad‐MAP with relative coordination. Circadian Per2 rhythms in R‐MAP rats were not affected in the SCN but were slightly phase‐advanced in the olfactory bulb (OB), caudate–putamen (CPU) and substantia nigra (SN) as compared with R‐Water rats. Following SCN lesion, R‐MAP‐induced MAO phase‐shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase‐shifted in the OB and SN as compared with SCN‐intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase‐shifts of the extra‐SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra‐SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker.     

Excessive disgust caused by brain lesions or temporary inactivations: mapping hotspots of the nucleus accumbens and ventral pallidum

Disgust is a prototypical type of negative affect. In animal models of excessive disgust, only a few brain sites are known in which localized dysfunction (lesions or neural inactivations) can induce intense ‘disgust reactions’ (e.g. gapes) to a normally pleasant sensation such as sweetness. Here, we aimed to map forebrain candidates more precisely, to identify where either local neuronal damage (excitotoxin lesions) or local pharmacological inactivation (muscimol/baclofen microinjections) caused rats to show excessive sensory disgust reactions to sucrose. Our study compared subregions of the nucleus accumbens shell, ventral pallidum, lateral hypothalamus, and adjacent extended amygdala. The results indicated that the posterior half of the ventral pallidum was the only forebrain site where intense sensory disgust gapes in response to sucrose were induced by both lesions and temporary inactivations (this site was previously identified as a hedonic hotspot for enhancements of sweetness ‘liking’). By comparison, for the nucleus accumbens, temporary GABA inactivations in the caudal half of the medial shell also generated sensory disgust, but lesions never did at any site. Furthermore, even inactivations failed to induce disgust in the rostral half of the accumbens shell (which also contains a hedonic hotspot). In other structures, neither lesions nor inactivations induced disgust as long as the posterior ventral pallidum remained spared. We conclude that the posterior ventral pallidum is an especially crucial hotspot for producing excessive sensory disgust by local pharmacological/lesion dysfunction. By comparison, the nucleus accumbens appears to segregate sites for pharmacological disgust induction and hedonic enhancement into separate posterior and rostral halves of the medial shell.     

Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release. The exposure permanently influenced neuronal representation of the sound frequency and intensity, resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate–intensity functions and an increased spontaneous activity. The effect was general and non‐specific, spanning the entire hearing range – no changes specific to the frequency band of the target stimuli were found. The alterations depended on the activity of animals during the enrichment – a higher activity of rats in the stimulus–reward paradigm led to more profound changes compared with the treatment when the stimulus–reward paradigm was not used. Furthermore, the exposure in early life led to permanent changes in response parameters, whereas the application of the same environment in adulthood influenced only a subset of the examined parameters and had only a temporary effect. These findings indicate that a rich and stimulating acoustic environment during early development, particularly when reinforced by positive feedback, may permanently affect signal processing in the subcortical auditory nuclei, including the excitatory thresholds of neurons and their frequency and intensity resolution.     

Gender differences in autoimmune disease

Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease.     

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14‐positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8‐positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8‐positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process.     

Endourological Treatment of Foreign Bodies in the Urinary System

Background and Objectives:

In this retrospective study, nature, clinical presentations, diagnostic modalities, and endoscopic treatment of urinary system foreign bodies were evaluated.

Methods:

A total of 8 cases were treated with endoscopic surgery between February 15, 2007 and June 12, 2012. Clinical findings, radiologic diagnosis, and management were reviewed.

Results:

We observed that urinary tract foreign bodies were generally secondary to iatrogenic causes; however, bladder/urethral foreign bodies could also be due to self-insertion. Clinical findings were different secondary to their location in the urinary system. All foreign bodies were treated endoscopically.

Conclusions:

Foreign bodies of the urinary system can successfully be treated with endoscopic modalities without any complications.     

Comparison of helicopter versus ground transport for the interfacility transport of isolated spinal injury

Background contextThe use and need of helicopter aeromedical transport systems (HEMSs) in health care today is based on the basic belief that early definitive care improves outcomes. Helicopter aeromedical transport system is perceived to be safer than ground transport (GT) for the interfacility transfer of patients who have sustained spinal injury because of the concern for deterioration of neurologic function if there is a delay in reaching a higher level of care. However, the use of HEMS is facing increasing public scrutiny because of its significantly greater cost and unique risk profile.PurposeThe aim of the study was to determine whether GT for interfacility transfer of patients with spinal injury resulted in less favorable clinical outcomes compared with HEMS.Study design/settingRetrospective review of all patients transferred to a Level 1 trauma center.Patient samplePatients identified from the State Trauma Registry who were initially seen at another hospital with an isolated diagnosis of injury to the spine and then transferred to a Level 1 trauma center over a 2-year period.Outcome measuresNeurologic deterioration, disposition from the emergency department, in-hospital mortality, interfacility transfer time, hospital length of stay, nonroutine discharge, and radiographic evidence of worsening spinal injury.MethodsPatients with International Classification of Diseases, Ninth Revision (ICD-9) codes for injury to the spine were selected and records were reviewed for demographics and injury details. All available spine radiographs were reviewed by an orthopedic surgeon blinded to clinical data and transport type. Chi-square and t tests and multivariate linear and logistic regression models were done using STATA version 10.ResultsA total of 274 spine injury patients were included in our analysis, 84 (31%) of whom were transported by HEMS and 190 (69%) by GT. None of the GT patients had any deterioration in neurologic examination nor any detectable alteration in the radiographic appearance of their spine injury attributable to the transportation process. Helicopter aeromedical transport system resulted in significantly less transfer time with an average time of 80 minutes compared with 112 minutes with GT (p<.001). Ultimate disposition included 175 (64%) patients discharged to home, 15 (5%) expired patients, and 84 (31%) discharged to extended care facilities. After adjusting for patient age and Injury Severity Score, the use of GT was not a significant predictor of in-hospital mortality (odds ratio, 1.4; 95% confidence interval, 0.3–5), hospital length of stay (11.2+1.3 vs. 9.5+0.8 days, p=.3), or nonroutine discharge (odds ratio, 1.1; 95% confidence interval, 0.5–2.2).ConclusionsGround transport for interfacility transfer of patients with spinal injury appears to be safe and suitable for patients who lack other compelling reasons for HEMS. A prospective analysis of transportation mode in a larger cohort of patients is needed to verify our findings.