Sedation and Acute Encephalopathy in a Pediatric Patient Following Ingestion of Delta-8-Tetrahydrocannabinol Gummies

BACKGROUND Delta-8 tetrahydrocannabinol (delta-8 THC) is an isomer of delta-9-tetrahydrocannabinol (delta-9 THC), the primary psychoactive cannabinoid in the marijuana plant. Typically found at lower concentrations in marijuana, delta-8 THC exhibits psychoactive properties similar to delta-9 THC. Products containing delta-8 THC are readily available across the US and currently there is a lack of available confirmatory testing specific to delta-8 THC as there is cross-reactivity to other naturally occurring cannabinoids in standard immunoassays. Pediatric exposures to this substance are on the rise. CASE REPORT We present a case with laboratory confirmation of a previously healthy 2-year-old girl ingesting approximately 15 mg/kg of delta-8 THC gummies. The patient arrived minimally responsive and requiring intubation for encephalopathy. Laboratory confirmation of delta-8 THC exposure is not routinely available with common testing modalities. A urine drug screen preformed in the hospital was positive for delta-9 THC. With the collaboration of the Drug Enforcement Administration\u27s Toxicology Testing Program, detection and confirmation of delta-8 THC was performed in the serum and urine using liquid chromatography-quadrupole time-of-flight mass spectrometry. CONCLUSIONS The prevalence of delta-8 THC-containing products in the illicit drug market is increasing rapidly. Delta-8 THC products are now available in gas stations and in headshops. The clinical presentation of delta-8 THC exposure is similar to known effects of delta-9 THC exposure. These similarities limit the clinicians\u27 abilities to determine the specific substance ingested. Symptomatic and supportive care remains an effective treatment for cannabinoid toxicity

Oncolytic viruses derived from the gamma34.5-deleted herpes simplex virus recombinant R3616 encode a truncated UL3 protein.

Replication-competent herpes simplex virus (HSV-1) mutants are used in clinical trials in the experimental treatment of cancer. Mutants G207, HSV1716, NV1020, and Oncovex GM-CSF share in common a defect in one or both copies of the gene encoding the neurovirulence factor, ICP34.5, and are thus neuroattenuated. These viruses are acknowledged to differ from one another (a) in the specific types of mutations intentionally introduced during their derivation and (b) in the inherent genetic differences retained from the different parent strains used in their construction. Unintended mutations are expected to emerge at some low frequency during the selection for and passage of mutant viruses. Here we demonstrate that during the construction of the oncolytic virus R3616, a nonsense mutation arose in an untargeted region of the HSV-1 genome that resulted in a substantial truncation of the viral protein known as UL3. This report is the first published documentation that oncolytic herpesviruses developed and used in clinical trials contain adventitious mutations. The implications of these findings for the characterization and development of vectors proposed for use in clinical trials are discussed

Microglial activation and antioxidant responses induced by the Parkinson's disease protein α-synuclein.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder typified by tremor, rigidity, akinesia and postural instability due in part to the loss of dopamine within the nigrostriatal system. The pathologic features of this disorder include the loss of substantia nigra dopamine neurons and attendant striatal terminals, the presence of large protein-rich neuronal inclusions containing fibrillar α-synuclein and increased numbers of activated microglia. Evidence suggests that both misfolded α-synuclein and oxidative stress play an important role in the pathogenesis of sporadic PD. Here we review evidence that α-synuclein activates glia inducing inflammation and that Nrf2-directed phase-II antioxidant enzymes play an important role in PD. We also provide new evidence that the expression of antioxidant enzymes regulated in part by Nrf2 is increased in a mouse model of α-synuclein overexpression. We show that misfolded α-synuclein directly activates microglia inducing the production and release of the proinflammatory cytokine, TNF-α, and increasing antioxidant enzyme expression. Importantly, we demonstrate that the precise structure of α-synuclein is important for induction of this proinflammatory pathway. This complex α-synuclein-directed glial response highlights the importance of protein misfolding, oxidative stress and inflammation in PD and represents a potential locus for the development of novel therapeutics focused on induction of the Nrf2-directed antioxidant pathway and inhibition of protein misfolding

Microglial activation and antioxidant responses induced by the Parkinson's disease protein α-synuclein.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder typified by tremor, rigidity, akinesia and postural instability due in part to the loss of dopamine within the nigrostriatal system. The pathologic features of this disorder include the loss of substantia nigra dopamine neurons and attendant striatal terminals, the presence of large protein-rich neuronal inclusions containing fibrillar α-synuclein and increased numbers of activated microglia. Evidence suggests that both misfolded α-synuclein and oxidative stress play an important role in the pathogenesis of sporadic PD. Here we review evidence that α-synuclein activates glia inducing inflammation and that Nrf2-directed phase-II antioxidant enzymes play an important role in PD. We also provide new evidence that the expression of antioxidant enzymes regulated in part by Nrf2 is increased in a mouse model of α-synuclein overexpression. We show that misfolded α-synuclein directly activates microglia inducing the production and release of the proinflammatory cytokine, TNF-α, and increasing antioxidant enzyme expression. Importantly, we demonstrate that the precise structure of α-synuclein is important for induction of this proinflammatory pathway. This complex α-synuclein-directed glial response highlights the importance of protein misfolding, oxidative stress and inflammation in PD and represents a potential locus for the development of novel therapeutics focused on induction of the Nrf2-directed antioxidant pathway and inhibition of protein misfolding