Roman Bux

Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

Abstract:  Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N‐acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post‐transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time‐of‐death groups (night/dawn/day/dusk) and analyzed for daytime‐dependent changes in phosphorylated AANAT (p31T‐AANAT) and in acetyl‐serotonin‐methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T‐AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T‐AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T‐AANAT and ASMT were often found to colocalize in cellular rod‐like structures that were also partly immunoreactive for the pinealocyte process‐specific marker S‐antigen (arrestin) in both, human and sheep pinealocytes. Protein–protein interaction studies with p31T‐AANAT, ASMT, and S‐antigen demonstrated a direct association and formation of robust complexes, involving also 14‐3‐3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T‐AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.

Sudden cardiovascular death associated with sexual activity

In recent discussions about potency-enhancing drugs such as sildenafil, health hazards associated with sexual activity have attracted increasing attention (1). In a medicolegal postmortem study performed in the Center of Legal Medicine at the University Hospital in Frank furt/Main over a 33-year period (1972–2004), about 32,000 forensic autopsies revealed 68 (0.22%) natural deaths occurring during sexual activity. Except for 5 women (7.4%; average age 39.8 years), in most cases, men were involved (92.6%; average age 59.1 years). The most frequent cause of death was myocardial infarction (n=28; 41.2%). In three cases, pericardial tamponade accompanied by myomalacia were observed. In 20 patients (29.4%), coronary artery disease (CAD) without signs of acute myocardial infarction (MI) was diagnosed. The medical history of 19 of the deceased indicated previous MI. There were seven cerebral hemorrhages (10.3%). The annual incidence of sudden cardiovascular death during sexual activity is estimated to be 1.9 per 1000 autopsies for men and 0.16 per 1000 autopsies for women (1). It is necessary to inform patients with CAD about prodromes and risk in relation to any form of physical and/or emotional stress.

Day–night expression patterns of clock genes in the human pineal gland

Abstract:  Rhythm generation within the mammalian circadian system is achieved by clock genes and their protein products. As an integral part of this system, the pineal gland serves the need to tune the body to the temporal environment by the rhythmic synthesis and release of melatonin. A number of human disorders and syndromes are associated with alterations in circadian rhythms of clock genes and their protein products and/or a dysfunction in melatonin synthesis. In the human, little is known about the molecular signature of time management. Pineal tissue from regular autopsies was allocated to asserted time‐of‐death groups (dawn, day, dusk, night), and analyzed by RT‐PCR, immunoblotting, immunohistochemistry, and confocal laser scanning microscopy for expression of clock genes. Despite the observed diurnal rhythms in activity of the arylalkylamine N‐acetyltransferase and in melatonin content, mRNA levels for the clock genes Period1, Cryptochrome1, Clock, and Bmal1, and also amounts of corresponding clock gene proteins showed no differences between time‐ of‐death groups. In contrast, a time‐of‐day‐dependent nucleocytoplasmic shuttling of clock gene proteins was detected. These data confirm the minor importance of a transcriptional regulation for dynamics in the human pineal gland, and offer a novel twist in the molecular competence of clock gene proteins.

Elektrowaffe ADVANCED TASER M 26 Funktionsweise, Wirksamkeit und Kasuistik

ZusammenfassungDer ADVANCED TASER M 26 ist eine Elektrowaffe, aus der mittels komprimiertem Stickstoff zwei kleine Pfeile verschossen werden, die über 6,40 m lange Drähte mit der Waffe verbunden bleiben. Nach deren Auftreffen werden elektrische Impulse in Form sog. T-Wellen übertragen, die die Erregungsleitung im Nervengewebe überlagern (electromuscular disruption, EMD) und so zu einem kurzzeitigen Verlust der Muskelkontrolle führen. Die waffenrechtliche Einordnung des Gerätes ist noch umstritten, es dürfte sich nach derzeitiger Auffassung, wie auch bei herkömmlichen Elektroschockgeräten, am ehesten um ein Hieb- und Stoßgerät nach § 1 Abs. 7 Satz 2 WaffG handeln. Bei dem deutschlandweit ersten Einsatz des Gerätes durch einen Polizeibeamten gelang es – nach erfolglosen Verhandlungen – einen psychisch kranken Mann zu überwältigen, der drohte, sich mit einem Messer zu verletzen und aus dem 5. Oberstock zu stürzen. Weder unmittelbar nach dem Vorfall, noch drei Tage danach wurden klinisch nachweisbare Nebenwirkungen festgestellt.AbstractThe Advanced Taser M 26 is a conducted energy weapon that shoots two small arrows up to 6.40 meters using compressed nitrogen. The arrows are connected to the weapon by insulated wire. After the arrows hit the target the weapon transmits electric impulses, called T-waves that interfere with the electric impulses used by the human nerve system to communicate with the skeletal muscles (electro-muscular disruption, EMD). Therefore the human target immediately looses control of his body and falls to the ground unable of any coordinated action. We report about an incident, where a 37-year-old man threatened to jump out of a 6th floor window. Police negotiators failed to convince the man to surrender. When finally the situation escalated and the man directly headed towards the open window a member of the special police forces fired his Advanced Taser M 26 at the man who was hit in the lateral part of the right abdomen and below the right knee joint, initially collapsed and could be fixed on the floor by police officers. He was conscious and able to walk. The man complained of feeling pressure in his chest under physical strain. At the cardiological department an ECG at rest on the day of the incident and three days later as well as a long-term ECG showed no pathological findings.

Plötzlicher Tod einer 12-Jährigen mit klinisch inapparenter Myokarditis unter psychischer und physischer Belastung

ZusammenfassungEin 12-jähriges klinisch gesundes Mädchen brach, nachdem es von einem PKW auf dem Bürgersteig verfolgt worden war, plötzlich tot zusammen. Bei der Obduktion zeigten sich eine deutliche Rötung der Atemwege, ein hochgradiges Lungenödem und eine akute Blutstauung der Organe des großen und kleinen Kreislaufs sowie die Zeichen des ausgeprägten Hirndruckes, jedoch keine sichere Todesursache. Die toxikologischen Untersuchungen verliefen negativ.Histologisch fand sich v. a. in der Muskulatur des rechten Herzventrikels eine perivaskulär betonte retikuläre Fibrose mit einem sehr schütteren lymphozytären Infiltrat, das ganz überwiegend aus CD3-positiven T-Zellen bestand. Die Lungen wiesen neben einer ausgeprägten Vermehrung des bronchusassoziierten Lymphgewebes eine diskrete interstitielle Pneumonie auf. Der im Myokard mittels “nested PCR” geführte Nachweis von viraler RNA des Koxsackievirus B3 in niedriger Kopienzahl (Institut für Pathologie, Universität Tübingen) erlaubte in Übereinstimmung mit den histologischen Befunden die Diagnose einer in Abheilung befindlichen Koxsackievirus-B3-Myokarditis, die den Tod durch massive psychische und physische Belastung erklären kann.AbstractA 12-year-old, clinically healthy girl suddenly collapsed and died after having been chased on the pavement by a car. Autopsy revealed signs of inflammation of the upper and lower airways, distinct cardiac edema of the lungs, acute congestion of the abdominal organs and increased cerebral pressure. However, the cause of death was not clear. Toxicological analyses were negative.Histologically, reticular fibrosis of the right heart focuses on the perivascular regions with only few lymphocytes, immunohistochemically proven as CD3-positive T cells, was detected. The lungs showed a remarkable increase of the peribronchial lymphatic tissue and slight signs of interstitial pneumonia. Nested PCR revealed traits of viral RNA of coxsackievirus B3 in the myocardium. A coxsackievirus B3 myocarditis close to recovery was diagnosed, which was consistent with the histological findings, explaining the sudden unexpected death under severe psychic and physical stress.

Melatonin synthesis in the human pineal gland

The mammalian pineal organ is a peripheral oscillator, depending on afferent information from the so-called master clock in the suprachiasmatic nuclei of the hypothalamus. One of the best studied outputs of the pineal gland is the small and hydrophobic molecule melatonin. In all vertebrates, melatonin is synthesized rhythmically with high levels at night, signalling the body the duration of the dark period. Changes or disruptions of melatonin rhythms in humans are related to a number of pathophysiological disorders, like Alzheimers disease, seasonal affective disorder or the Smith-Magenis-Syndrome. To use melatonin in preventive or curative interferences with the human circadian system, a complete understanding of the generation of the rhythmic melatonin signal in the human pineal gland is essential.

A fatal search for worms—a peculiar electrical accident

A 32-year-old man used a self-made electrical instrument to collect earthworms for fishing. It consisted of a metal stick with a plastic handle. The stick was connected to a 10 m long wire which ended in a single-phase plug. After watering the lawn and connecting the plug to one phase of a socket (AC 220 V), he touched both the handle and the metal stick, presumably while trying to push it deeper into the soil. Through this procedure he closed the electrical circuit from his left hand to his bare feet standing on the wet lawn and was killed instantly. The autopsy revealed burn marks only on the left palm. Petechiae were found in the facial skin and the mucous membranes. The inner organs showed intensive signs of blood congestion. Toxicological analysis of blood, urine, gastric contents, liver and bile was negative. The calculated current of about 111 mA flowing through the body exceeded the range of 80-100 mA generally considered to be lethal.