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.

Body procurement in the Dr. Senckenbergische Anatomie in Frankfurt/Main after the Second World War - From unclaimed corpses to body bequests.

The present paper provides a detailed historical and numerical analysis of the processes regarding body procurement in a particular German anatomical institute, namely, the Dr. Senckenbergische Anatomie (DSA) in Frankfurt am Main. It covers the period from 1946 to 1980; i.e. the transitional phase during which unclaimed corpses were replaced by corpses stemming from body donors. The DSA is fortunate to possess the complete set of records spanning that period. Thus, we cannot only document the (failed) organizational and political efforts of the local anatomists and governmental agencies to uphold the unclaimed body system of old, but we can also present rather detailed data regarding the genesis of the system of body donations. In particular, we will provide evidence that this system was more or less self-generating, and that its emergence was not actively propagated by the local anatomists. Instead, it was triggered by both the media and by the donors themselves, with the latter acting as multipliers. In addition we provide, for the first time, data on the efficacy (in terms of "file corpses" vs. real corpses in anatomy) of a body donation system in Germany.

A complete situs inversus viscerum with hepatic, intestinal and renalvascular anomalies: one case report and review of the literatur

Situs inversus viscerum (SIV) is a rare congenital anomaly, which is still an intriguing phenomenon to anatomists and physicians alike. A complete SIV is characterized by a left-right transposition and mirror image of all thoraco-abdominal organs and their vasculature. The present report is based on one case with complete SIV, which was observed during the routine educational dissections of cadavers in the authors' Anatomy Department. A transposition of all truncal organs and their vasculature, and several variations of arteries and veins were present. The right branch of the proper hepatic artery was replaced by an artery that emanated from the superior mesenteric artery. The latter also released the inferior mesenteric artery. Additionally, a left accessory renal artery ran anterior to the inferior caval vein and posterior to the ureter to enter the hilum of the left kidney. There was also a variation in the anterior-posterior arrangement of the hilar structures of the left kidney. Additionally, a globally enlarged heart with coronary artery by-passes, a replaced aortic valve and an aortic arch aneurysm was observed. This case report is unique, as it presents a previously unreported co-incidence of SIV and hepatic, intestinal and renal vascular anomalies. It is important for the surgeon to be aware of such variations while planning an abdominal surgery in patients with SIV

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Recommendations of the working group of the Anatomische Gesellschaft on reduction of formaldehyde exposure in anatomical curricula and institutes.

The practice of human and veterinary medicine is based on the science of anatomy and dissection courses are still irreplaceable in the teaching of anatomy. Embalming is required to preserve body donors, for which process formaldehyde (FA) is the most frequently used and well characterized biocidal substance. Since January 2016, a new occupational exposure limit (OEL) for FA of 0.37mg/m3 issued by the European Committee on Hazardous Substances is obligatory since FA has been classified as a human 1B carcinogen. The anatomical institutes in the German-speaking region are called upon to consolidate efforts to reduce use of FA in anatomical curricula and body donations. As a result, the Anatomische Gesellschaft (AG) has formed a "Working Group for Reduction of Formaldehyde Exposure in Dissection Courses" tasked with discussion and recommendation of measures to reduce FA. Based on the assessment of the Working Group, the AG has issued an official opinion to the effect that, at this point in time, embalming of body donors without FA completely is not feasible. Therefore, a combination of approaches are to be used to reduce FA exposure, including technical and structural (architectural) adaptations, modification of protocols for fixation and preservation as well as organizational measures. One structural measure considered unavoidable is the integration of air supply and exhaust of individual dissecting tables into the ventilation system of the anatomy building. To embalm human body donors, intra-arterial perfusion fixation with up to 4% FA and a total fluid volume of 150mL/kg body weight will suffice. For animals where body weights and biology of bodies vary widely (i.e. special needs of fixation for ruminants, large animals as horses) perfusion fixation with up to 4% FA and a quantity of fixative solution of 10-15% of the body weight may be required. Preservation of body donors in storage (immersion) can be done with 40% ethanol or in a full bath preservation containing up to 2% FA. Corpse humidification in the dissecting room is possible with 2% phenoxyethanol, in each case without FA. In veterinary anatomy, microbiological burden is often higher and therefore might lead to a need of FA in long-time storage. Compliance with the current OEL in all institutes would appear to be feasible in combination with various organizational measures.

Robot-assisted percutaneous placement of K-wires during minimally invasive interventions of the spine.

Purpose: To assess the accuracy and time requirements of image-guided percutaneous K-wire insertion in the spine using an advanced robot assistance device for needle guidance and to demonstrate a radiation-free workflow for the physician. Material and methods: A planning CT-scan was acquired of a cadaver specimen and analyzed using a 3D-interventional software integrated in the robotic device. The optimal needle path was simulated and the needle holder of the robot was used for guidance during K-wire insertion. Twenty-four K-wires were inserted percutaneously in a transpedicular approach in the following vertebrae: thoracic (T) 2, 7-12 and lumbar (L) 1-5. A post-procedural CT scan was performed to analyze the accuracy of the K-wire insertion. Results: All procedures were carried out without any perforation of the pedicle wall. The mean duration of planning the intervention path was 2:54 ± 2:22 min, mean positioning time was 2:04 ± 0:42 min and the mean time for K-wire insertion was 2:13 ± 0:54 min. In total, the average intervention time was 7:10 ± 3:06 min per pedicle. Compared to the planning, the K-wire position showed a mean deviation of 0.5 mm in the vertical-axis and 1.2 mm in the horizontal-axis. The average intervention path length was 8.1 cm. Conclusion: Our findings show a high accuracy in robot-assisted K-wire insertion during spinal interventions without any exposure of the operator to radiation.

Notes on the history of the Dr. Senckenbergische Anatomie in Frankfurt/Main. Part I. Development of student numbers, body procurement, and gross anatomy courses from 1914 to 2013.

Until recently, it was believed that all internal documentation regarding student affairs and body procurement of the Dr. Senckenbergische Anatomie concerning the time before March 1944 - when the building was destroyed during an Allied air raid - was lost. A few years ago, however, we discovered stacks of old documents in the current anatomy building. These documents permitted a reconstruction (1) of the history of body procurement, student numbers and course management from 1914 to 1944, as well as (2) some aspects of the building's history in the time immediately after its destruction that have hitherto not been documented. In this paper (Part I), we will deal with the organizational history of the Dr. Senckenbergische Anatomie from 1914 to 2013, placing special emphasis on the development of the student population and body procurement, as well as on the major changes that occurred in the gross anatomy labs of the last century. More than 30,000 students were trained in the Dr. Senckenbergische Anatomie over the last 100 years, and more than 3000 bodies have been received. The number of incoming bodies has remained quite stable in all these years and is, on average, approximately 32 per year. The number of students entering the gross anatomy lab during that period, however, rose from less than 100 to more than 600. A companion paper (Part II) deals with the years of the Third Reich (1933-1945) in more detail.

Notes on the history of the Dr. Senckenbergische Anatomie in Frankfurt/Main. Part II. The Dr. Senckenbergische Anatomie during the Third Reich and its body supply.

In order to be able to understand how body supply was maintained at the Dr. Senckenbergische Anatomie from 1933 to 1945 - with special emphasis on victims of the National Socialist regime - we have collected information from various and often fragmentary sources. The documents reveal that during this period at least 474 bodies were brought to the anatomical institute. Among them were the bodies of at least 71 prisoners, 51 of whom had been executed, and the bodies of 8 inmates of (labor-) camps. 356 unclaimed bodies were received, some of them may stem from victims of "euthanasia" programs. The sources of 39, as of yet, unnamed bodies could not be verified. The current collections and the catalogs were screened for remains of victims of the National Socialist regime, but none were found. The vast majority of the bodies were used for teaching purposes. Hans Schreiber, one of the directors of the institute, whose biography is provided here, used at least 9 additional executed individuals for his research. Wherever possible, we have identified the victims of the National Socialist regime, executed persons and the inmates of (labor-) camps, whose bodies were used by the anatomists in Frankfurt, by name. Among the victims was Georg Fröba, a communist philanthropist, whose biography is provided.

Combining C-arm CT with a new remote operated positioning and guidance system for guidance of minimally invasive spine interventions.

OBJECTIVE: To report our experience using C-arm cone beam CT (C-arm CBCT) combined with the new remote operated positioning and guidance system, iSYS1, for needle guidance during spinal interventions. METHODS: A C-arm CBCT with a flat panel angiography system was acquired (Artis Zeego; Siemens Healthcare Sector, Forchheim, Germany). Reconstruction of CT-like images and planning of the needle path were performed using a common workstation. The needle holder of iSYS1 acted as a guide during insertion of Kirschner (K) wires. 20 percutaneous K wires were placed in the pedicles at T2-T3, T7-T12, and L1-L2 in a cadaver specimen. Postprocedure C-arm CBCT scans were obtained to confirm the accuracy of the K wire placement. RESULTS: All K wire placements were successfully performed. Mean planning time with Syngo iGuide was 4:16 min, mean positioning time of iSYS1 was 3:35 min, and mean placement time of the K wires was 2:22 min. Mean total intervention time was 10:13 min per pedicle. A mean deviation of 0.35 mm between the planned path and the placed K wire with a mean path length of 6.73 cm was documented. CONCLUSIONS: Our results demonstrate the potential of combining C-arm CBCT with iSYS1 for safe and accurate percutaneous placement of pedicle K wires in spinal interventions.

Novel, portable, cassette-sized, and wireless flat-panel digital radiography system: initial workflow results versus computed radiography.

OBJECTIVE: The purpose of this article is to compare workflow efficiency between a conventional computed radiography (CR) system and a novel, portable, cassette-sized, and wireless flat-panel digital radiography (DR) system. MATERIALS AND METHODS: Observational time-motion analyses were performed at one site at which CR and the new portable DR system are used concurrently. The workflow steps of both systems were identified and categorized to facilitate comparison. The times required for examination preparation, patient positioning, exposure, postacquisition processing, and the examination as a whole were recorded by a neutral observer. Timing differences between the CR and portable DR systems were compared, and all data were analyzed using commercially available statistical software. Nine general radiographic examination types were selected, with approximately 50 patients per examination type. RESULTS: A total of 941 examinations (CR, n = 474; portable DR, n = 467) were timed in this study. Total examination time differences between CR and portable DR system (mean, 26.44 seconds; median 26.99 seconds) were found to be statistically significant (p < 0.001), with DR proving faster than CR. The single largest contributor to the time difference between CR and portable DR was postacquisition processing (mean, 26.58 seconds; median, 25.91 seconds), which was a composite of multiple individual steps, including cassette transport (CR only, mean, 13.22 seconds; median, 12.74 seconds), cassette readout (mean, 10.15 seconds; median, 10.4 seconds), and postprocessing (mean, 3.21 seconds; median, 3.11 seconds). CONCLUSION: Overall radiographer time was significantly shorter when performing examination-related tasks with the novel, portable DR system than when performing comparable tasks with the CR system, a difference that appears to result largely from technology configuration.

Spatial and temporal expression patterns of Bmal delineate a circadian clock in the nervous system of Branchiostoma lanceolatum.

We cloned the homologue of the clock gene Bmal from a cephalochordate, Branchiostoma lanceolatum (syn. amphioxus). Amphioxus possesses a single copy of this gene (amphiBmal) that encodes for a protein of 649 amino acids, which is quite similar to BMALs of other chordates. The gene is expressed by a restricted cell group in the anterior vesicle of the neural tube, and its expression site coincides with that of another clock gene, namely, amphiPer. The expression of amphiBmal shows a rhythmic fluctuation that persists under constant darkness and is, thus, circadian. Similar to the situation in craniates, the peak phases of the amphiBmal and amphiPer expression are offset by 12 hours. Based on these observations and the putative homology between the diencephalon of vertebrates and the anterior vesicle of lancelets, we suggest a homology between the suprachiasmatic nucleus of craniates and the amphiBmal/amphiPer-expressing cell group of amphioxus.

Nocturnal behavior and rhythmic period gene expression in a lancelet, Branchiostoma lanceolatum.

The authors here present the first anatomical, molecular biological, and ethological data on the organization of the circadian system of a lancelet, Branchiostoma lanceolatum, a close invertebrate relative of vertebrates. B. lanceolatum was found to be a nocturnal animal and, since its rhythmic activity persisted under constant darkness, it also appears to possess an endogenous, circadian oscillator. The authors cloned a homolog of the clock gene Period (Per), which plays a central (inhibitory) role in the biochemical machinery of the circadian oscillators of both vertebrates and protostomians. This gene from B. lanceolatum was designated as amphiPer. Both the sequence of its cDNA and that of the predicted protein are more similar to those of the Per paralogs of vertebrates than to those of the single protostomian Per gene. A strong expression of amphiPer was found in a small cell group in the anterior neural tube. The amphiPer mRNA levels fluctuated in a rhythmic manner, being high early in the day and low late at night. The authors' data suggest a homology of the amphiPer expessing cells to the suprachiasmatic nucleus of vertebrates.

Cannabinoids attenuate norepinephrine-induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine N-acetyltransferase activity without involvement of cannabinoid receptors.

Cannabinoids modulate neuronal and neuroendocrine circuits by binding to cannabinoid receptors acting upon cAMP/Ca(2+)-mediated intracellular signaling cascades. The rat pineal represents an established model to investigate intracellular signaling processes because a well defined input, the neurotransmitter norepinephrine, is transformed via cAMP/Ca(2+)-dependent mechanisms into an easily detectable output signal, the biosynthesis of melatonin. Here we investigated the impact of cannabinoids on norepinephrine-regulated melatonin biosynthesis in the rat pineal. We demonstrated that treatment of cultured rat pineals with 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced norepinephrine-induced arylalkylamine N-acetyltransferase (AANAT) activity and melatonin biosynthesis. These effects were not mimicked by the cannabinoid receptor agonist WIN55,212-2 and were not blocked by cannabinoid 1 and 2 receptor antagonists. The cannabinoids used did not affect norepinephrine-induced increases in cAMP/Ca(2+) levels. Notably, cannabinoids were found to directly inhibit AANAT activity in lysates of the pineal gland. This effect was specific in so far as cannabinoids did not influence the activity of hydroxyindole-O-methyltransferase (HIOMT), the last enzyme in melatonin biosynthesis. Taken together, our data strongly suggest that cannabinoids inhibit AANAT activity and attenuate melatonin biosynthesis through intracellular actions without involvement of classical cannabinoid receptor-dependent signaling cascades.

Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation.

We have previously shown that the extracellular nucleoside triphosphate-hydrolyzing enzyme NTPDase2 is highly expressed in situ by stem/progenitor cells of the two neurogenic regions of the adult murine brain: the subventricular zone (type B cells) and the dentate gyrus of the hippocampus (residual radial glia). We explored the possibility that adult multipotent neural stem cells express nucleotide receptors and investigated their functional properties in vitro. Neurospheres cultured from the adult mouse SVZ in the presence of epidermal growth factor and fibroblast growth factor 2 expressed the ecto-nucleotidases NTPDase2 and the tissue non-specific isoform of alkaline phosphatase, hydrolyzing extracellular ATP to adenosine. ATP, ADP and, to a lesser extent, UTP evoked rapid Ca(2+) transients in neurospheres that were exclusively mediated by the metabotropic P2Y(1) and P2Y(2) nucleotide receptors. In addition, agonists of these receptors and low concentrations of adenosine augmented cell proliferation in the presence of growth factors. Neurosphere cell proliferation was attenuated after application of the P2Y(1)-receptor antagonist MRS2179 and in neurospheres from P2Y(1)-receptor knockout mice. In situ hybridization identified P2Y(1)-receptor mRNA in clusters of SVZ cells. Our results infer nucleotide receptor-mediated synergism that augments growth factor-mediated cell proliferation. Together with the in situ data, this supports the notion that extracellular nucleotides contribute to the control of adult neurogenesis.

Mechanisms regulating melatonin synthesis in the mammalian pineal organ.

The day/night rhythm in melatonin production is a characteristic feature in vertebrate physiology. This hormonal signal reliably reflects the environmental light conditions and is independent of behavioral aspects. In all mammalian species, melatonin production is regulated by norepinephrine, which is released from sympathetic nerve fibers exclusively at night. Norepinephrine elevates the intracellular cAMP concentration via beta-adrenergic receptors and activates the cAMP-dependent protein kinase A. This pathway is crucial for regulation of the penultimate enzyme in melatonin biosynthesis, the arylalkylamine N-acetyltransferase (AANAT); cAMP/protein kinase A may, however, act in different ways. In ungulates and primates, pinealocytes constantly synthesize AANAT protein from continually available Aanat mRNA. During the day-in the absence of noradrenergic stimulation-the protein is immediately destroyed by proteasomal proteolysis. At nighttime, elevated cAMP levels cause phosphorylation of AANAT by protein kinase A. This posttranslational modification leads to interaction of phosphorylated AANAT with regulatory 14-3-3 proteins, which protect AANAT from degradation. Increases in AANAT protein are paralleled by increases in enzyme activity. Stimulation of the cAMP/protein kinase A pathway may also activate pineal gene expression. In rodents, transcriptional activation of the Aanat gene is the primary mechanism for the induction of melatonin biosynthesis and results in marked day/night fluctuations in Aanat mRNA. It involves protein kinase A-dependent phosphorylation of the transcription factor cyclic AMP response element-binding protein (CREB) and binding of phosphorylated CREB in the promoter region of the Aanat gene. In conclusion, a common neuroendocrine principle, the nocturnal rise in melatonin, is controlled by strikingly diverse regulatory mechanisms. This diversity has emerged in the course of evolution and reflects the high adaptive plasticity of the melatonin-generating pineal organ.

Dephosphorylation of pCREB by protein serine/threonine phosphatases is involved in inactivation of Aanat gene transcription in rat pineal gland.

The rat pineal gland is a suitable model to investigate neurotransmitter-controlled gene expression, because it is well established that the stimulation of melatonin biosynthesis by norepinephrine (NE) depends on the activation of the gene that encodes arylalkylamine N-acetyltransferase (AANAT), the melatonin rhythm enzyme. The mechanisms responsible for downregulation of Aanat transcription are less clear. In this in vitro study we investigated the role of pCREB dephosphorylation for termination of Aanat gene transcription. Immunosignals for pCREB, strongly induced after NE stimulation, rapidly decreased after withdrawal of NE. The immunoreactivity of the inhibitory transcription factor ICER increased twofold after NE treatment for 6 h, but did not change within 30 min after removal of the stimulus. Application of protein serine/threonine phosphatase (PSP) inhibitors prevented pCREB dephosphorylation and blocked the decreases in Aanat mRNA levels, AANAT protein amount and melatonin biosynthesis all of which occurred rapidly after NE withdrawal. PSPs in the rat pineal gland were characterized by immunocytochemistry and immunoblotting. NE-stimulation for 8 h induced accumulation of PSP1-catalytic subunit (CSU) in pinealocyte nuclei, but did not affect the distribution of PSP2A-CSU. The results identify dephosphorylation of pCREB by PSPs as an essential mechanism for downregulation of Aanat transcription in the rat pineal gland.

Norepinephrine-dependent phosphorylation of the transcription factor cyclic adenosine monophosphate responsive element-binding protein in bovine pinealocytes.

Norepinephrine (NE)-dependent activation of transcription factors is of central importance for the rhythmic production of melatonin in the rodent pineal gland. At variance with rodents, NE regulates melatonin biosynthesis through post-translational mechanisms in ungulates, and it is not yet known whether transcription factors play any role in ungulate pineal functions. Here, we investigated in isolated bovine pinealocytes the NE-dependent phosphorylation of the transcription factor cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB) and compared the effects of NE with those of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Treatment with 10(-7) m NE for 30 min induced a strong nuclear phosphorylated CREB (pCREB) immunoreaction in cells that were identified as pinealocytes by immunocytochemical demonstration of serotonin, a pinealocyte-specific marker. Immunoblots showed that the NE-induced immunoreaction was due to phosphorylation of the transcription factor CREB and another protein, presumably the activating transcription factor 1 (ATF-1). 10(-7) m isoproterenol (ISO) or 10(-5) m forskolin mimicked the response to NE indicating that NE acts through the beta-adrenergic/cAMP pathway. Also 10(-7) m PACAP, but not 10(-7) m VIP-enhanced CREB phosphorylation; however, only a subpopulation of cells was responsive to PACAP. Our results suggest that, irrespective of whether or not melatonin production is controlled via transcriptional mechanisms, NE-induced CREB phosphorylation represents a very conserved element in pineal physiology of mammals because NE increases pCREB levels in all mammalian species investigated so far. However, the genes targeted by pCREB may vary from one mammalian species to the other. Our results also suggest that transcription factors other than pCREB, like ATF-1, may play a role in pineal functions of mammals.

Signal transduction and regulation of melatonin synthesis in bovine pinealocytes: impact of adrenergic, peptidergic and cholinergic stimuli.

Limited studies of the regulation of pineal melatonin biosynthesis in ungulates indicate that it differs considerably from that in rodents. Here we have investigated several signal transduction cascades and their impact on melatonin synthesis in bovine pinealocytes. Norepinephrine increased the intracellular calcium ion concentration ([Ca2+]i) via alpha(1)-adrenergic receptors. Activation of beta-adrenergic receptors enhanced cAMP accumulation and rapidly elevated arylalkylamine N-acetyltransferase (AANAT) activity and melatonin secretion. The beta-adrenergically evoked increases in AANAT activity were potentiated by alpha(1)-adrenergic stimulation, but this was not seen with cAMP or melatonin production. PACAP treatment caused small increases in cAMP, AANAT activity and melatonin biosynthesis, apparently in a subpopulation of cells. VIP and glutamate did not influence any of these parameters. Activation of nicotinic and muscarinic acetylcholine receptors increased [Ca2+]i, but did not alter cAMP levels, AANAT activity or melatonin production. Our study reveals that discrete differences in pineal signal transduction exist between the cow and rodent, and emphasizes the potential importance that the analysis of ungulate pinealocytes may play in understanding regulation of pineal melatonin biosynthesis in primates and man, whose melatonin-generating system appears to be more similar to that in ungulates than to that in rodents.