Intentional overdose of glargine insulin: Determination of the parent compound in postmortem blood by LC-HRMS

Insulin glargine is a long-acting insulin analog that is converted after enzymatic cleavage of the arginine pair of the β-chain into its main metabolite M1 (21^A-Gly-insulin), which is responsible for the hypoglycemic activity. In all the overdose cases described in the literature, only M1 concentrations have been reported, whereas insulin glargine was always absent or below the limit of quantitation. In this study, we present a case of suicide of a young nurse by injection of insulin glargine in which the parent molecule was found at a toxic concentration in blood. The determination and the discrimination of insulin glargine from human insulin and other synthetic analogs in the blood specimen were performed by liquid chromatography coupled to high-resolution mass spectrometry (Waters XEVO G2-XS QToF) and extraction after precipitation in the presence of bovine insulin (internal standard), with a mixture of acetonitrile/methanol +1% formic acid followed by purification on solid phase extraction cartridges C18. Glargine insulin tested highly positive in the blood with a concentration of 1.06 mg/L. Due to the difficulty in obtaining a M1 pure standard, the metabolite could not be dosed. This unique presence of the parent molecule, reported for the first time, can be explained by inter-individual variability in the rate of conversion to metabolite. Intravenous injection versus subcutaneous injection can also explain the presence of insulin glargine. Finally, the dose injected may have been so high that saturation of the proteolytic enzymes responsible for conversion to M1 should have occurred.     

Radiodense bullet wipe around osseous entrance gunshot wounds

“Bullet wipe” is the material deposited by a bullet on any surface with which it comes into contact after it is fired and may contain debris from the gun barrel, including particles of primer and metal fragments from previously fired bullets. X‐ray analysis is a non‐destructive method by which traces of metallic elements can be visually detected. The analysis of osseous defects for radiodense bullet wipe (RBW) assists in determining the presence or absence of perforating gunshot wounds, especially in fragmented, skeletonized remains. The aim of our current study was to determine the frequency of RBW around entrance firearms injuries that perforated bone. We prospectively analyzed entrance gunshot wounds for RBW over a three‐year period using digital X‐ray analysis (n = 59). We retrospectively reviewed the corresponding autopsy reports to determine the frequency of RBW by biologic sex, reported ancestry, age‐at‐death, location of wound, manner of death, range of fire, bullet caliber, and presence of bullet jacket. Data were analyzed by Fisher's exact test or Chi‐square test with significance levels accepted at p < 0.05. RBW was present in 66% (n = 39) of examined cases. Decedent characteristics did not significantly alter RBW distribution, including biologic sex (p = 0.75), reported ancestry (p = 0.49), and age‐at‐death (p = 0.43). Additionally, the location of the osseous entrance gunshot wound, manner of death, range of fire, and cartridge caliber did not affect RBW detection. All cases involving non‐jacketed rounds (n = 5) showed RBW (p = 0.30). To our knowledge, this study is the first to report the frequency of RBW detection from osseous entrance gunshot wounds.     

Nation Branding as Nation Building: China’s Image Campaign

This paper illustrates the links between China’s nation building exercises and its efforts to promote the country as a ‘brand’. By using the examples of the Shanghai Expo, China’s national image films and the revival of Confucius, I show how Chinese soft power is both inward and outward looking. Understanding this dual role of soft power is important in comprehending the underlying motivations behind China’s attempts to create and manage its identity as orderly, prosperous and legitimate.     

Intellectual property rights on creativity and heritage: the case of the fashion industry

Recently, as different projects aiming to define and reinforce property rights in the fashion industry have been elaborated and discussed, a lot of papers have been dedicated to the question of property rights in this industry. Our paper considers the problems from a specific point of view; it focuses on the relation between property rights and creativity. If property rights allow the allocation of the majority of standard industrial goods without any special difficulty, however, when they are applied to creative goods, new problems arise. Then, for us, the persistence of a low system of IPRs in the fashion industry does not mainly derive from its efficiency but from the characteristics of the inputs that are used in the creative production process. They constitute strong constraints for defining, entitling, legitimating, enforcing, valuating and exchanging property rights. Thus, the different economic actors develop different kinds of strategic behaviour in order to obtain earnings and can try to protect copyrights, trademarks, new assets, old assets (heritage), private or collective assets, and so on. The institutional characteristics of this specific industry—such as the models of management, the type of ownership, the size of the firms, … lead to different historical models of management through IPRs. Peculiarly, the financial groups that integrate fashion into the new luxury industries currently try to implement new IPRs and to move towards a stronger system of IPRs but the management model of the street fashion puts an obstacle to this project.     

Analysis of active ricin and castor bean proteins in a ricin preparation, castor bean extract, and surface swabs from a public health investigation

In late February 2008, law enforcement officials in Las Vegas, Nevada, discovered in a hotel room, a copy of The Anarchist Cookbook, suspected castor beans and a "white powder" thought to be a preparation of ricin. Ricin is a deadly toxin from the seed of the castor bean plant (Ricinus communis). The United States regulates the possession, use, and transfer of ricin and it is the only substance considered a warfare agent in both the Chemical and the Biological Weapons Conventions. Six samples obtained from the hotel room were analyzed by laboratories at the Centers for Disease Control and Prevention using a panel of biological and mass spectrometric assays. The biological assays (real time-PCR, time resolved fluorescence and cytotoxicity) provided presumptive evidence of active ricin in each of the samples. This initial screen was followed by an in-depth analysis using a novel, state-of-the-art mass spectrometry-based ricin functional assay and high sensitivity tandem mass spectrometry for protein identification. Mass spectrometric analysis positively identified ricin and confirmed that in each of the samples it was enzymatically active. The tandem mass spectrometry analysis used here is the most selective method available to detect ricin toxin. In each sample, ricin was unequivocally identified along with other R. communis plant proteins, including the highly homologous protein RCA120. Although database searches using tandem mass spectra acquired from the samples indicated that additional controlled substances were not present in these samples, the mass spectrometric results did provide extensive detail about the sample contents. To the best of our knowledge following a review of the available literature, this report describes the most detailed analysis of a white powder for a public health or forensic investigation involving ricin.     

A case of fatal overdose involving both hydromorphone and kratom

Kratom is a plant originating in Southeast Asia that has been used for its dose-dependent stimulant and opioid effects. The main active compound in kratom is mitragynine, an alkaloid with affinity for the mu-opioid receptor. Toxicity and fatalities related to kratom use have increased substantially in recent years. In this case report, we describe a 44-year-old man who was found deceased in bed. The only significant finding at autopsy was abdominal distension with >4 L of ascites. Toxicology testing was performed on femoral blood which showed 79 ng/mL of hydromorphone, 560 ng/mL of mitragynine, and 240 ng/mL of olanzapine. In addition, creatinine and urea in vitreous humor were significantly elevated, consistent with renal impairment. Death was attributed to hydromorphone toxicity with mitragynine being a contributing factor.     

Phenibut screening and quantification with liquid chromatography–tandem mass spectrometry and its application to driving cases

An analytical strategy for identification by an LC–MS/MS multitarget screening method and a suitable LC–MS/MS based quantification were developed for the psychotropic drug phenibut. The samples analyzed were collected during traffic control and were associated with driving under the influence of drugs. A positive sample for phenibut was identified in a single case of driving under the influence. The quantification revealed a drug concentration of 1.9 μg/mL. An interaction with blood alcohol (BAC = 0.10%) was discussed as the explanation of the way of driving and deficit manifestations observed (swaying, nystagmus, quivering of the eyelid, and reddened eyes). According to the available information, the quantified phenibut concentration could be explained by an intake of four tablets (self-reported) during the day containing 250 mg of the drug. Chromatography was performed with a Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm analytical column, and a buffer system consisted of 10 mM ammonium acetate and 0.1% acetic acid (v/v) included in mobile phases marked as A (H₂O/methanol = 95/5, v/v) and B (H₂O/methanol = 3/97, v/v). An effective limit of detection (LOD = 0.002 μg/mL) could be achieved for the multitarget screening method. The quantification of phenibut was performed on a second LC–MS/MS system with LOD/LOQ values of 0.22/0.40 μg/mL. Since phenibut quantification data are rare, the presented information can be used with caution for evaluation of positive cases in the future.     

Fat embolism syndrome associated with atraumatic compartment syndrome of the bilateral upper extremities: An unreported etiology

Fat embolism syndrome (FES) is a potentially life-threatening condition that develops when fat embolism leads to clinical symptoms and multisystem dysfunction. The classic triad of respiratory distress, neurologic symptoms, and petechial rash are non-specific, and the lack of specific laboratory tests makes the diagnosis of FES difficult. Although FES is most common after long bone fractures, multiple conditions some of which are atraumatic have been associated with the development of FES. We report a case of FES that occurred in the setting of a non-traumatic compartment syndrome of the upper extremities. The pathologic and clinical findings, pathophysiology, diagnostic challenges, and pathologic methods to properly diagnose FES are discussed with a review of the relevant literature. This case highlights the importance of the autopsy in making a diagnosis of FES in cases where death could otherwise be incorrectly attributed to multi-organ system failure, shock, or sepsis.