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Genetic Control of Endotoxin Responsiveness: The Lps Gene Revisited
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Stefanie N. Vogel, Nayantara Bhat, Danielle Malo, Salman T. Qureshi
An important cautionary point with regard to the Lpsd phenotype is that the defect appears to be highly selective for protein-free LPS preparations. Most LPS preparations, particularly commercial ones, are contaminated with significant levels of endotoxin-associated proteins, which can be largely eliminated through repurification (19). These endotoxin-associated proteins are highly bioactive in and of themselves and when purified (i.e., rendered free of contaminating LPS) are equipotent in cells derived from Lpsn and Lpsd strains; like LPS, they exhibit synergistic bioactivity in the presence of IFN-γ (20). Hence, when considering papers that claim LPS responsiveness in Lpsd mice or in cells derived from Lpsd strains, it is necessary to evaluate the source and purity of the LPS used in the study. A corollary to this caveat can be found in studies in which C3H/HeJ mice or their cells respond differentially to a non-LPS stimulant. In such cases, sufficient information should be provided to established that low levels of contaminating endotoxin are not contributing to the observed response pattern (such as reagent testing with the Limulus amebocyte lysate assay). A good example of these issues can be found in a recent publication by Dunn and Chuluyan (21). Administration of a commercial preparation of LPS to C3H/HeN and C3H/HeJ mice led to the intriguing finding that the C3H/HeJ strain, as expected, failed to mount a normal catecholamine and pituitary-adrenal response, whereas induction of indolaminergic responses by this LPS preparation were similar in the two strains. In the absence of information on the purity of this LPS preparation or confirmation using a second, more purified LPS preparation, it is difficult to interpret these findings. Certainly, the more interesting possibility is that the induction of tryptophan and the downstream serotonin catabolite 5-HIAA represents a signaling pathway that is not disrupted by the expression of the Lpsd allele in vivo. However, in the absence of this critical information, the reader is left to wonder if contaminating moieties within the LPS preparation are able to elicit the indolaminergic pathway independently of LPS.
A Systematized Review of Drug-checking and Related Considerations for Implementation as A Harm Reduction Intervention
Published in Journal of Psychoactive Drugs, 2023
Francesca Giulini, Eamon Keenan, Nicki Killeen, Jo-Hanna Ivers
In most countries, individuals are at risk of criminal prosecution when handling illicit drugs (Burkhart 2001; Palamar, Salomone, and Barratt 2020). Consequently, DC providers internationally have designed their service so volunteers can never be considered in possession of a substance when handling the sample in question unless it is unidentified (Gerace et al. 2019; Sage and Michelow 2016). This limits DCS analysis options, excluding any methods that require preparation. In response, DCS in Italy employed portable RAMAN spectroscopy (Fornero et al. 2017), allowing DC through plastic without the sample leaving the patron’s hands (Gerace et al. 2019). Similarly, ANKROS uses reagent testing as it requires minimal preparation and no sample handling by volunteers (Sage and Michelow 2016). The illegality of transporting illicit drugs in Italy has made it more challenging to establish fixed-site DCS (Fornero et al. 2017).
Levamisole-adulterated cocaine poses a concern during the COVID-19 pandemic
Published in Journal of Addictive Diseases, 2020
Konrad Marski, Antonio Meaiki, Martin Shanouda
In the context of the COVID-19 pandemic caused by SARS-CoV-2 we in the medical profession have been especially concerned about our patients with compromised immune systems. There is, however, a cause of immunocompromise which may escape the attention of both practitioners and researchers: consumption of adulterated recreational drugs. Cocaine in particular is noteworthy for being, at the time of writing, near uniformly adulterated with the medication levamisole.1 This medication is used as an anthelmintic and is listed on the World Health Organization’s List of Essential Medicines.2 Used in doses of 50 mg to 150 mg (adult dosing) it is indicated for the treatment of ascariasis and other infections caused by hookworms and pinworms.2 Used in the illicit drug trade it provides a filler material for cocaine which reacts similarly to that drug on basic reagent testing.3 For this reason as well as a potential synergistic recreational effect levamisole has been added to cocaine hydrochloride prior to departure from distribution sites in Mexico. Thus the majority of cocaine found outside of that country and the few cocaine-producing countries will contain levamisole in some proportion.1,4 With a levamisole content of upwards of ten percent by mass, one gram of cocaine has the potential to include upwards of 100 mg of levamisole.4 And with re-dosing being common with cocaine use it is not possible to discount a substantial exposure to levamisole even if individual doses are smaller.
Deaths related to MDMA (ecstasy/molly): Prevalence, root causes, and harm reduction interventions
Published in Journal of Substance Use, 2018
In addition to on-site testing, kits can be purchased online so that users are able to test the purity of their MDMA in the privacy of their home. Personal test kits are available online and can be purchased via private retailers or e-commerce sites such as Amazon and eBay. A commonly used kit is the Marquis Reagent testing kit, which uses sulfuric acid and formaldehyde to test for certain compounds (DanceSafe, 2017). This type of personal test kit turns various colors to signal the presence of potentially harmful contaminants, as well as MDMA. Other types of reagent tests can be used to test for different drugs, depending on the preference of the user. A single personal testing kit, which is good for about 50 tests, can be purchased for approximately $20 and is usually delivered in a discrete unmarked box (DanceSafe, 2017).