The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

Challenges and implementation of the German maternity protection act for female medical students in macroscopic anatomical education.

Background: Recent decades have seen controversial discussions on the validity of dissection courses in medical education, with alternative programs tested for various reasons. On April 1, 2015 the classification of formaldehyde as a hazardous substance was upgraded by the EU, leding to some universities precluding the participation of pregnant and breastfeeding students in dissection course. However, the revision to the Maternity Protection Act, implemented in Germany on January 1, 2018, now protects student mothers from being disadvantaged in their studies as a consequence of their pregnancy or breastfeeding. Therefore, universities must offer alternatives to dissection courses using formaldehyde to these female students. Project description: As an alternative to regular dissection courses, which use the abovementioned chemical, the Centre for Anatomy at Charité has opted for developing dedicated courses for student mothers. These new courses use plastinated prosection material instead of formalin-treated cadavers of body donors. As the core of the anatomical education takes place during the third and fourth semester in the current curriculum of human medicine at Charité the alternative courses are limited to those two semesters. Additionally, alternative exams at the end of both semesters had to be developed. The alternative courses were designed to offer pregnant and breastfeeding students a study program as close as possible to the one in which their peers learn human anatomy. Results: For the new courses, plastinates had to be produced and further specimens are still needed. Additionally required sets of bones, models and radiological images were readily available at the Centre for Anatomy. The planning and conceptualization of the courses took half a year of intense preparation. The courses for the third and fourth semester were first running during summer semester 2017. There is a clear demand for courses among pregnant and breastfeeding students. At least 5 student participants per course were registered, corresponding to every fortieth female student in their semester cohorts. The highest number of student participants was 13 in one course so far. The performances of the participants in the anatomical examinations were matching that of students attending the regular courses. Discussion: The alternative macroscopic anatomy courses enable the implementation of the revised Maternity Protection Act. The targeted student group is highly satisfied with the offered alternative courses. Considering the number of participants and their examination performance so far, the Centre for Anatomy regards the efforts involved in planning and implementing the courses as justified. The courses allow pregnant and breastfeeding students to address the same anatomical themes at the same time as their fellow students. However, due to restricted flexibility of plastinates and because students cannot prepare specific anatomical structures independently the scope of topographic learning is limited. That being said, well-produced plastinates can display anatomical structures which often cannot be dissected in regular courses. The alternative macroscopic anatomy courses using plastinates constitute suitable alternatives to the regular dissection courses with formalin-treated cadavers for pregnant and breastfeeding students.

The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices.

BACKGROUND AND PURPOSE: Gamma oscillations are fast rhythmic fluctuations of neuronal network activity ranging from 30 to 90 Hz that establish a precise temporal background for cognitive processes such as perception, sensory processing, learning, and memory. Alterations of gamma oscillations have been observed in schizophrenia and are suggested to play crucial roles in the generation of positive, negative, and cognitive symptoms of the disease. EXPERIMENTAL APPROACH: In this study, we investigated the effects of the novel antipsychotic cariprazine, a D3 -preferring dopamine D3 /D2 receptor partial agonist, on cholinergically induced gamma oscillations in rat hippocampal slices from treatment-naïve and MK-801-treated rats, a model of acute first-episode schizophrenia. KEY RESULTS: The D3 receptor-preferring agonist pramipexole effectively decreased the power of gamma oscillations, while the D3 receptor antagonist SB-277011 had no effect. In treatment-naïve animals, cariprazine did not modulate strong gamma oscillations but slightly improved the periodicity of non-saturated gamma activity. Cariprazine showed a clear partial agonistic profile at D3 receptors at the network level by potentiating the inhibitory effects when the D3 receptor tone was low and antagonizing the effects when the tone was high. In hippocampal slices of MK-801-treated rats, cariprazine allowed stabilization of the aberrant increase in gamma oscillation power and potentiated resynchronization of the oscillations. CONCLUSION AND IMPLICATIONS: Data from this study indicate that cariprazine stabilizes pathological hippocampal gamma oscillations, presumably by its partial agonistic profile. The results demonstrate in vitro gamma oscillations as predictive biomarkers to study the effects of antipsychotics preclinically at the network level.

Effects of single swim stress on changes in TRPV1-mediated plasticity in the amygdala.

By examining the involvement of transient receptor potential vanilloid type 1 (TRPV1) in the stress modulation of learning and memory processes in mice, we evaluated the effects of endovanilloid N-oleoyldopamine (OLDA) on the long-term potentiation (LTP) of the lateral nucleus of the amygdala (LA). After high-frequency stimulation of external capsule fibers we found that LA-LTP is reduced in OLDA-treated slices derived from adult C57BL/6 control mice. The specificity of the TRPV1 receptor activation by OLDA was confirmed by blocking the OLDA-induced inhibitory effect on LA-LTP with the specific TRPV1 receptor antagonist AMG 9810. The specificity of OLDA was further supported by using TRPV1 deficient mice, where the effect of OLDA on LA-LTP was missing. Following exposure to a forced swim test (FST) OLDA enhanced LA-LTP in control but not TRPV1-deficient mice. The results also show that a short period of acute stress significantly impairs LA-LTP. Since we have recently shown the involvement of cannabinoid CB1 receptors in the mediation of capsaicin-induced inhibitory effects on LA-LTP ([23] Zschenderlein et al., 2011), it is reasonable to assume that the OLDA-induced enhancement of LA-LTP after the forced swim test can be attributed to the up-regulation of TRPV1 and the action of ligands such as anandamide on TRPV1. As a result, stimulation of TRPV1 receptors rescues LTP in slices derived from swim-stressed mice.

Different isoforms of nitric oxide synthase are involved in angiotensin-(1-7)-mediated plasticity changes in the amygdala in a gender-dependent manner.

BACKGROUND: The amygdala receives afferent sensory input and processes information related to hydromineral balance. Angiotensin acts on and through the amygdala to stimulate thirst and sodium appetite. In addition, different angiotensins seem to play a role in cognition and learning mechanisms by acting on and through the amygdala. Recently, we showed that angiotensin-(1-7) (Ang-(1-7)) enhances the magnitude of long-term potentiation (LTP) in the lateral nucleus of the amygdala (LA) via the Mas receptor. METHODS: Extracellular field potentials were measured in the LA. RESULTS: LA-LTP induced by stimulation of the external capsule was nitric oxide (NO)-dependent because the NO synthase (NOS) inhibitor L-NAME reduced LA-LTP. The LA-LTP was also reduced in both male and female nNOS and eNOS knockout mice. In male eNOS(-/-) mice, Ang-(1-7) enhanced LA-LTP, whereas the LTP-enhancing effect of Ang-(1-7) was missing in female eNOS(-/-) mice. Therefore, the LTP-enhancing effect of Ang-(1-7) was mediated by eNOS in females. In contrast, Ang-(1-7) strongly enhanced the LTP in nNOS(-/-) females, whereas the effect of Ang-(1-7) was missing in nNOS(-/-) males. Thus, Ang-(1-7) induced an increase in the magnitude of LTP via the involvement of nNOS in males. CONCLUSION: Our data support not only the hypothesis that NO contributes to plasticity changes in the lateral amygdala, but also show for the first time a gender-dependent involvement of different isoforms of NOS in the mediation of Ang-(1-7) on LTP in the amygdala.

Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

Genetic control of leucocyte--endothelial cell interaction in collagen-induced arthritis.

OBJECTIVE: Despite considerable work on defining disease pathways, several aspects of collagen-induced arthritis (CIA) remain poorly defined, in particular those contributing to the initiation phase of the disease. It is thought that in CIA the activation of circulating leucocytes, their interaction with the endothelial lining followed by subsequent transendothelial migration and infiltration into tissue represents the first and determining step in a complex sequence of processes mediating tissue injury. In this study we attempted to define the genetic basis of this stage of disease using genetic linkage studies, in-vivo imaging and expression profiling. METHODS: A genome scan with 132 informative markers was performed on 155 (DBA/1JxFVB/N) F2 mice. Linkage analysis was performed by combining genotyping data from the genome scan and the phenotypic data of leucocyte adherence, leucocyte rolling fraction, functional capillary density, centre line red blood cell velocity and capillary width as well as the expression level of the selected genes Cd44, Il13ralpha1, Ccr3, Defb3, Sele, Sell, Selp, Xcl1, Il1beta, Tnfalpha and Ifngamma as traits. RESULTS: Multiple classic quantitative trail loci (QTL) controlling leucocyte-endothelial cell interactions were identified on chromosomes 8 and 17 as well as expression QTL controlling the expression of several differentially expressed adhesion molecules and cytokines on chromosomes 1, 2, 5, 6, 7, 8, 12, 15, 16 and 17. CONCLUSION: The study describes for the first time QTL controlling the CIA initiating leucocyte-endothelial cell interaction.