Cytotoxic activity of human dendritic cells induces RIPK1-dependent cell death.

Dendritic cells (DCs), as potent phagocytes engulf dead cells and present peptide fragments of tumor antigens or pathogens derived from infected cells to naïve CD8+ T-lymphocytes. Dendritic cells can also induce apoptosis in target cells, thus getting an opportunity to sample their microenvironment. Here, we present that the supernatants of LPS- or CL075-activated DCs induced cell death in different cell lines, but during the differentiation to mature DCs, they lost their cytotoxic potential. Dexamethasone-pre-treated tolerogenic DCs induced less intensive death indicating that the tissue microenvironment can downregulate DC-mediated killing. Exploring the signaling of DC-induced cell death, we observed that the supernatant of activated DCs induced TNF-dependent cell death, since TNF antagonist blocked the cytotoxic activity of DCs, contrary to inhibitors of Fas and TRAIL receptors. We identified that the DC-induced killing is at least partially a RIPK1-dependent process, as RIPK1 positive target cells were more susceptible to DC-induced cell death than their RIPK1 deficient counterparts. Moreover, both the elevated phosphorylation of RIPK1 and the increase in RIPK1-caspase-8 interaction in target cells suggest that RIPK1-mediated signals contribute to DC supernatant-induced cell death. We also proved that the cytotoxic activity of DC-derived supernatant induced apoptosis in the target cells and not necroptosis, as it was completely abrogated with the pan caspase inhibitor (Z-VAD), while the necroptosis inhibitor (Nec-1) had no effect. Our work revealed that the supernatant of activated DCs induces the apoptosis of target cells in a RIPK1-dependent manner. This phenomenon could be relevant for the initiation of cross-presentation and may broaden the plethora of cytotoxic mechanisms acting against tumor cells.

Suicide by Intentional Air embolism.

Venous air embolism occurs when air enters the venous system. The main causes of venous air embolism include medical procedures, neck and head trauma, and injuries of the genitals. Self-induced suicidal (and intentional) air embolism is extremely rare. The authors report a rare case of a suicidal air embolism committed using a self-made tool composed of a plastic bottle and an infusion set, injecting nearly 2000 mL of air into the cubital vein. The toxicological analysis suggested that midazolam, together with air, was also injected into the circulation using the same bottle and infusion set.

PCR-based identification of drowning: four case reports.

Proper diagnosis in drowning victims is often difficult due to the lack of signs specific to drowning. The diatom test is a widely used procedure for the diagnosis. Some types of water contain only minimal amounts of diatom cells which may provide false-negative results, while a negative diatom test result does not exclude drowning. In proving drowning, we used a polymerase chain reaction (PCR)-based biological method in addition to the conventional methods. DNA was extracted from postmortem spleen tissues and water of the drowning site. Samples were tested with algae (diatoms and small green algae)- and cyanobacteria (blue-green algae)-specific primers. We present here multiple drowning cases in which diatom tests of the postmortem tissue samples and the water were negative. In each case, the presence of phytoplanktonic DNA strengthened the autopsy diagnosis of drowning even in the absence of visible diatoms. In the future, the PCR method may be of consideration as a possible supplement of the diatom test in the examination of presumed drowning cases.

The rate of RNA degradation in human dental pulp reveals post-mortem interval.

Post-mortem interval (PMI) is the amount of time elapsed since the time of death. Over the years, many methods were developed to assess PMI, but their precision and time frame of applicability are often limited. Our present pilot study aimed to prove if RNA degradation of human dental pulp can be used for PMI estimation. RNA was isolated from the pulps of healthy wisdom teeth and premolars. RNA degradation was determined as RNA integrity number (RIN) with Agilent Bioanalyzer and subsequently by amplification of different length products by PCR after reverse transcription. The RNA integrity analysis allowed us to determine the time of post-mortem interval with high confidence level in the first 21 days. With the PCR-based method, we were able to perform a crude estimation of incubation time of teeth between 20 and 42 days post extraction. These results show that this method might be a promising new tool for PMI estimation despite the limitations.

Drowning-related fatalities during a 5-year period (2008-2012) in South-West Hungary--a retrospective study.

The purpose of the present study was to investigate all the drowning-related cases in South-West Hungary between 2008 and 2012. It is a retrospective and descriptive study of 114 drowning-related deaths during that 5-year period. The investigation includes both unintentional and intentional drowning cases. We found that the most considerable risk factor of drowning in this area of Hungary is alcohol consumption, because in more than half of the cases the victims were under the influence of alcohol. We also concluded that more than two third of the cases included males. The cause of drowning in younger victims was mostly accident. In both genders subjects aged 50-70 had the highest risk of drowning in the period investigated. Seniors frequently committed suicide by drowning. Drowning deaths occurred in all types of water, mostly in lakes, rivers, canals and other types of catchment in the vicinity of victims' homes (most commonly in wells). This study might help to understand the circumstances and the causes leading to drowning and it may draw the attention to the possible preventive interventions.