Ventral striatum regulates behavioral response to ethanol and MDMA combination.

Our previous studies consistently showed that MDMA-induced locomotor hyperactivity is dramatically increased by coadministration of ethanol (EtOH) in rats, indicating possible potentiation of MDMA abuse liability. Thus, we aimed to identify the brain region(s) and neuropharmacological substrates involved in the pharmacodynamics of this potentiation. We first showed that potentiation of locomotor activity by the combination of ip administration of EtOH (1.5 g/kg) and MDMA (6.6 mg/kg) is delay sensitive and maximal when both drugs are injected simultaneously. Then, we used the 2-deoxyglucose quantitative autoradiography technique to assess the impact of EtOH, MDMA, or their combination on local cerebral metabolic rates for glucose (CMRglcs). We showed a specific metabolic activation in the ventral striatum (VS) under MDMA + EtOH versus MDMA or EtOH alone. We next tested if reversible (tetrodotoxin, TTX) or permanent (6-hydrodoxyopamine, 6-OHDA) lesion of the VS could affect locomotor response to MDMA and MDMA + EtOH. Finally, we blocked dopamine D1 or glutamate NMDA receptors in the VS and measured the effects of MDMA and MDMA + EtOH on locomotor activity. We showed that bilateral reversible inactivation (TTX) or permanent lesion (6-OHDA) of the VS prevented the potentiation by EtOH of MDMA-induced locomotor hyperactivity. Likewise, blockade of D1 or NMDA receptors in the VS also reduced the potentiation of MDMA locomotor activity by EtOH. These data indicate that dopamine D1 and glutamate NMDA receptor-driven mechanisms in the VS play a key role in the pharmacodynamics of EtOH-induced potentiation of the locomotor effects of MDMA.

An overview of forensic operations performed following the terrorist attacks on November 13, 2015, in Paris.

On the evening of November 13, 2015, the city of Paris and its surroundings was hit by a series of attacks committed by terrorist groups, using firearms and explosives. The final toll was 140 people deceased (130 victims and 10 terrorists or their relatives) and more than 413 injured, making these attacks the worst mass killings ever recorded in Paris in peacetime. This article presents the forensic operations carried out at the Medicolegal Institute of Paris (MLIP) following these attacks. A total of 68 autopsies of bodies or body fragments and 83 external examinations were performed within 7 days, and the overall forensic operations (including formal identification of the latest victims) were completed 10 days after the attacks. Over this period, 156 body presentations (some bodies were presented several times) were provided to families or relatives. Regarding the 130 civilian casualties, 129 died from firearm wounds and one died from blast injuries after an explosion. Of the 10 terrorists or their relatives who were killed, eight died from suicide bombing, one was shot by police and one died from crush injuries due to partial collapse of a building following the police raid against a terrorist's hideout after the attacks. All mass shootings were perpetrated with AK-47 or Zastava M70 assault rifles using 7.62 mm × 39 mm cartridges. In the case of ballistic injuries, death was most often obviously caused by craniocerebral injuries, extensive organ lacerations and/or massive haemorrhage. Among the terrorists killed by bombing, the lesion patterns were body transection, multiple amputations, extreme organ lacerations and the presence of foreign bodies owing to the shrapnel load (steel nuts, glass fragments) or the explosive charge fastening system of the devices. This discussion highlights the particular difficulties of interpretation encountered within the framework of ballistic injuries, a conclusion that should lead to a modest and realistic approach in these exceptional situations where forensic operations involve a very large number of victims in a constrained time.

Terrorist attacks: cutaneous patterns of gunshot and secondary blast injuries.

Terrorist attacks have been on the rise. During the recent terrorist attacks in France, terrorists perpetrated their acts using weapons of war, as well as explosive charges. These two modes of action, when combined, can create skin lesions with similar macroscopic appearances, which can sometimes go unnoticed because of body fragmentation. A total of 68 autopsies, 83 external examinations, 140 standard radiographic examinations, and 49 computed tomography (CT) scans were performed over 7 days during the 2015 terrorist attacks in France. Bodies were injured by firearms and shrapnel-like projectiles. We analysed the clinical findings for the secondary blast cutaneous lesions from the explosive devices and compared these lesions with ballistic-related lesions to highlight that patterns can be macroscopically similar on external examination. Secondary blast injuries are characterised by penetrating trauma associated with materials added to explosive systems that are propelled by explosive air movement. These injuries are caused most often by small, shrapnel-like metallic objects, such as nails and bolts. Propulsion causes ballistic-type injuries that must be recognised and distinguished from those caused by firearm projectiles. Differentiating between these lesions is very difficult when using conventional criteria (size, shape, number and distribution on the body) with only external examination of corpses. This is why the particularities of these lesions must be further illustrated and then confirmed by complete autopsies and radiological and anatomopathological examinations.Key pointsWhen occurring simultaneously in terrorist attacks, injuries caused by secondary blasts appear as cutaneous wound patterns that can be macroscopically very similar to those caused by firearm projectiles.The criteria usually found in the literature for distinguishing these two types of projectiles may be difficult to use.It is important in these difficult situations to benefit from systematic postmortem imaging.Systematic autopsy and then anatomopathological analyses of the orifices also help determine the cause of the wounds.

Terrorist explosive belt attacks: specific patterns of bone traumas.

In cases of terrorist bomb attacks, the issue of victim identification is the principal aim. For investigators and justice, terrorists must also be identified in a timely manner. The fragmentation of bodies caused by explosive devices however makes this operation difficult. The cases presented correspond to six autopsies of perpetrators carrying explosives. Their explosive belts produced different body sections on areas correlated with the location on the body of carrying explosive charges. Indeed, cross-sectional areas are the signature of the level of explosive devices on the body, and some fracture features through the damage of certain areas of constitutional weaknesses are specific elements to consider. These elements can allow a quick distinction between victims and terrorists, in order to assist in the medico-legal process of identification.

The potential of forensic analysis on human bones found in riverine environment.

Human remains found in aquatic contexts are frequently recovered incomplete and badly decomposed, and therefore present a challenge for medico-legal institutes as their possibilities of analysis for identification and investigation of cause and manner of death are limited. This article aims to demonstrate the potential of forensic examination and analyses (DNA, toxicology, diatoms and entomology) on a set of bones recovered from a river in Strasbourg and the possibility to trigger identification of the victim and circumstances of death despite the state of decomposition and incompleteness of remains.

Sexual abuse and anti-wrinkle cream: evidence from octocrylene.

We report an alleged case of sexual assault in which an anti-wrinkle cream could have been used as a lubricant. Three anorectal samples taken from the victim were given to us in an attempt to document the presence of remains of the cream involved. After examining the composition of the cream, octocrylene (OCT) was selected as the most relevant marker for this analysis. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for identification of OCT. Anorectal samples were diluted with methanol and injected onto an Acquity BEH C18 column using a gradient mode with 0.1% formic acid/acetonitrile as the mobile phase. Data were acquired using positive electrospray ionization and multiple reaction monitoring. Three transitions were selected for OCT (m/z 362.2>250.0, m/z 362.2>232.0 and m/z 362.2>204.0). The analysis of the cream seized at the offender's home confirmed the presence of OCT as an ingredient, and the analysis of extracts from the anorectal samples also allowed the formal identification of OCT. These results strongly suggest that a cosmetic containing octocrylene as an ingredient has in fact been applied to the anus of the alleged victim.

Suicide by skull stab wounds: a case of drug-induced psychosis.

Suicide by stabbing to the head and/or driving sharp objects into the skull is of extreme rarity. This article reports the case of a 27-year-old man, who committed suicide by multiple knife stabs and cuts to the head, the torso, one shoulder and the forearms. Autopsy showed a perforating wound of the skull and the 10-cm long broken blade of the knife being still embedded in the right temporal lobe of the brain. The deceased had no history of psychiatric illness but was currently treated by mefloquine, a quinine derivative associated with a high rate of psychiatric adverse effects. Toxicological examination confirmed a recent intake of mefloquine together with chloroquine, another antimalarial drug. To our knowledge, this is the first report of a completed suicide with very strong evidence of mefloquine implication. Discussion focuses upon mefloquine-induced psychiatric disorders and highlights the importance of performing toxicological investigations in cases of unusual suicides.

Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA.

Ecstasy (3,4-methylenedioxymethylamphetamine; MDMA) is a popular club drug often taken with ethanol (EtOH). We recently found EtOH potentiated the psychomotor effects of MDMA in rats. This potentiation could reflect pharmacodynamic or/and pharmacokinetic processes. To test the latter hypothesis, rats were injected i.p. with 6.6 or 10 mg/kg MDMA with or without 1.5 g/kg EtOH, and were killed at 5, 15 or 60 min after injection. MDMA, its primary metabolite, 3,4-methylenedioxyamphetamine (MDA), and EtOH concentrations were determined in the plasma and the hippocampus, frontal cortex and striatum at each time-point. EtOH potentiated MDMA-induced hyperactivity mainly during the first 60 min post-administration. Fifteen and 60 min after treatment with MDMA and EtOH, MDMA concentrations were greater than after MDMA alone in the blood and the three brain regions examined. EtOH, however, did not increase the fraction of MDMA converted to MDA, as shown by unaltered MDA/MDMA ratios at either MDMA dose. Interestingly, when combined with EtOH, the distribution of MDMA and MDA in the brain was not homogeneous. Concentrations of both were much higher in the striatum and cortex, than in the hippocampus. Thus, at least part of the potentiation of the MDMA-induced hyperlocomotion by EtOH might be the result of a higher concentration of MDMA and metabolites in the blood and brain. Our results present clear evidence that EtOH increases brain and blood concentrations of MDMA and leads to the possibility of both enhanced MDMA-based neurotoxicity and increased liability for abuse.

Determination of cannabinoids in whole blood by UPLC-MS-MS.

An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed and validated for the simultaneous determination of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in whole blood. Samples were prepared by protein precipitation followed by solid-phase extraction. Data were acquired using positive electrospray ionization and multiple reaction monitoring. Two transitions were selected for THC (m/z 315.0 > 193.0 and m/z 315.0 > 122.7) and THC-COOH (m/z 345.0 > 299.0 and m/z 345.0 > 327.0), and one transition was chosen for 11-OH-THC (m/z 331.0 > 313.0). Deuterated analogues of each analyte were used as internal standards for quantification. Run time was 10 min. Limits of quantification (LOQ) were 0.05 ng/mL for THC, 0.1 ng/mL for 11-OH-THC, and 0.2 ng/mL for THC-COOH. Linearity was established from LOQ to 50 ng/mL for each substance (r(2) always > 0.999). Accuracy ranged from 96 to 106%, and imprecision was less than 10% for all analytes. The UPLC-MS-MS method was found to be sensitive, specific, and rapid because it requires no derivatization step. It can be an alternative to gas chromatography-mass spectrometry for the determination of cannabinoids in whole blood.

Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination.

RATIONALE: In our previous work, we showed that ethanol (EtOH) potentiates 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperlocomotion while protecting against its hyperthermic effects. Whereas the effect on activity were found on all days (although declining over the three first days), the protection against hyperthermia completely disappeared on the second day. The latter effect was previously thought to reflect tolerance to ethanol or the combination, per se. OBJECTIVE: In the present study, we changed the treatment regimen to irregular and longer intervals between treatments (48, 120, and again 48 h) to check if tolerance was still observed. RESULTS: We found progressive sensitization of locomotor activity to EtOH (1.5 g/kg, i.p.)+MDMA (6.6 mg/kg, i.p.), and a partial EtOH protection against MDMA-induced hyperthermia that persisted after the first drug challenge day. When the monoamine neurotransmitters, dopamine, and serotonin were assessed 2 weeks after treatment, we found no consistent effect on the concentration of any of these neurotransmitters, whatever the treatment. Similarly, we found that regional brain concentrations of MDMA were not significantly affected by EtOH at a 45-min post-treatment delay; however, the overall ratio of the metabolite 3,4-methylenedioxyamphetamine (MDA) to MDMA was lower (overall, -16%) in animals treated with the combination compared to MDMA alone, indicating possible contribution of pharmacokinetic factors. This difference was especially marked in the striatum (-25%). CONCLUSIONS: These findings shed new light on the consequences of EtOH-MDMA, taken together at a nearly normal ambient temperature, both in terms of motivation and potential risks for recreational drug users.

Homicide by manual occipitoatlantal dislocation.

Occipitoatlantal dislocation is usually seen as a fatal injury in traffic accidents and has rarely been reported as a consequence of a homicide. The authors report the case of a women presenting a fatal occipitoatlantal dislocation, the circumstances of which pointed to a homicidal origin. Blood extravasation surrounding the muscles of the posterior part of the neck as well as abnormal mobility of the cranio-cervical joint was noted during autopsy; thus a complete dissection of this region was performed. This led to the finding of a fracture of the left occipital condyle and of the left superior articular facet of the atlas. This case clearly demonstrates the need to perform a large, systematic, posterior approach to the upper cervical spine, completed by the opening of the skull around the posterior fossa, when injury to the cranio-cervical junction is suspected. In these cases, the classic anterior approach give poor information and poor dissection possibilities.

Buprenorphine in drug-facilitated sexual abuse: a fatal case involving a 14-year-old boy.

The first case involving repetitive sexual abuse linked to the use of buprenorphine is reported. Under the tradename Subutex, buprenorphine is largely used for the substitution management of opiate-dependent individuals, but it can also be easily found on the black market. A 14-year-old boy was found dead at the home of a well-known sex offender of minors. At the autopsy, no particular morphological changes were noted, except for pulmonary and visceral congestion. There was no evidence of violence, and no needle marks were found by the pathologist. Toxicological analyses, as achieved by liquid chromatography-mass spectrometry, demonstrated both recent and repetitive buprenorphine exposure in combination with nordiazepam. Buprenorphine concentrations were 1.1 ng/mL and 23 pg/mg in blood and hair, respectively. The boy's death was attributed to accidental asphyxia in a facilitated repetitive sexual abuse situation due to the combination of buprenorphine and benzodiazepines, even at therapeutic concentrations. The use of buprenorphine as a sedative drug was not challenged by the perpetrator.

Homicide attempt with a Japanese samurai sword.

The use of Japanese swords for homicidal attempts is rare. A Japanese samurai sword is a sharp and cutting object. When faced with the use of this weapon, one must distinguish between stabs and incised wounds. Incised wounds can rarely lead to death, but because of the size of the weapon, stabs usually cause much more serious injuries. Stabs also imply a penetrating movement, whereas incised wounds can be the consequence of protective circular blows. Therefore, it is important to distinguish clinically between these two kinds of wounds. We report a case where the perpetrator argued he had given a circular blow, unfortunately hitting the victim. The pieces of evidence are discussed.

Penetration of a piece of World War II rifle grenade initially suspected as a stab wound.

The authors report the case of a 58-year-old man found dead by his son in the forest where he had gone to cut wood for winter. Initial examination showed an upper left laterocervical wound compatible with a stab wound. Radiography and autopsy performed the next day showed a piece of metal located in the left part of the occipital bone, associated with a half-ring fracture of the occipital bone and consequent diffuse subarachnoid hemorrhage. Death was attributed to a spinal shock after impact at the cervicocephalic junction. Investigators returned to the scene and found a few more metal elements and also a 20-cm deep and 40-cm wide crater underneath a fire the deceased had set. Army experts concluded that the metal pieces belonged to an ATM 9 antitank rifle grenade used by the U.S. Army during World War II. Death was considered accidental, the deceased having unfortunately set a fire over the grenade.