Journal of Medical Toxicology最新文献

Introduction: Pet Poison Helpline^® (PPH), a 24/7 international animal poison control center has observed a significant and rising number of exposures detailing multisystemic signs and adverse outcomes associated with oclacitinib maleate (Apoquel^®) overdoses.

Methods: Pet Poison Helpline^® utilizes a proprietary electronic database which was retrospectively reviewed for oclacitinib maleate exposure information from January 2022 to November 2024 through their toxicology consultation service.

Results: Market entry and distribution of chewable oclacitinib maleate occurred in October 2023. In the year following, there was a 299% increase in calls to PPH from inadvertent exposure. Of the 417 symptomatic cases reviewed, 63 cases were symptomatic cats, and 354 cases were symptomatic dogs. Multi-system organ involvement, including neurological, gastrointestinal, cardiovascular, renal, hepatic, and ocular signs, as well as laboratory abnormalities were observed.

Discussion: Introduction of a chewable formulation in October 2023 likely attributed to a marked increase in exposures. Accompanying this rise in overdose exposures, a notable escalation in multisystemic effects was seen, including neurological, gastrointestinal signs, cardiovascular disturbances, ocular irregularities, renal and hepatic injury, and complete blood count (CBC) hematological abnormalities. Treatment is largely symptomatic and supportive therapy.

Conclusion: The increased occurrence of exposures to oclacitinib maleate underscores necessity for additional research of JAK inhibitors in animals to better understand and address oclacitinib maleate toxicosis.

Poisoning is a major public health issue and one of the leading causes of injury related death in the US. Poisonings result from intentional or unintentional use of prescription drugs or illicit overdose including opioids, inhalation of toxic fumes, ingestion of contaminated food or drinking water, and envenomations. The cost of poisonings to US health care is large, especially when considering the costs of addiction and illicit opioids. As specially trained physicians, medical toxicologists play a major role in the treatment and care of poisoned patients while improving patient care, population health, and health care systems related to chemical exposures and poisonings including prevention. They also play a major role in the opioid epidemic and in caring for patients with opioid use disorder and substance use disorders more broadly. Regardless of these important roles, the recognition and knowledge of the value that medical toxicologists provide to health and the health care system is limited. As reimbursement becomes linked to outcome in a value-based care (VBC) market, medical toxicologists must continue to demonstrate their value to stakeholders. The American College of Medical Toxicology (ACMT) has long recognized the need for medical toxicologists to articulate their value and to advocate for themselves, the profession, and for the patients they serve. To that end, modeling infectious disease (ID) efforts in establishing value for their specialty, this paper outlines the 'value' of medical toxicologists in improving patient outcomes, and their positive impact on population health and health care systems.

These are the selected abstracts for the 2025 American College of Medical Toxicology (ACMT) Annual Scientific Meeting, which will take place from April 4-6, 2025, in Vancouver, Canada. This year's accepted abstracts include original research studies, including contributions from the Toxicology Investigators Consortium (ToxIC), and clinically significant case reports highlighting unique toxicologic phenomena. These presentations reflect the continued growth and impact of toxicology research, providing attendees with valuable insights into emerging trends, novel treatment strategies, and evolving best practices in the field.

Introduction: Acetaminophen (APAP) overdose remains a common cause of liver injury, primarily due to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). This study sought to investigate APAP-induced platelet aggregation in vitro, and the implication of CYP2E1 in the metabolism of APAP and hepatic cell toxicity.

Methods: Co-cultures of platelets and hepatic cells that do not (HepG2) and do express CYP2E1 (HepG2^E47) were exposed to APAP (0-20 mM), NAPQI (0-250 µM), APAP in the absence/presence of inhibitors of glutathione (50 μM buthionine sulphoximine (BSO)), or APAP in the absence/presence of inhibitors CYP2E1 (chlormethiazole (CMZ, 100 µM), or 4-methylpyrazole (4-MP, 5 mM)). Platelet aggregation, cell viability and reactive oxygen species (ROS) were analyzed. Changes in platelet aggregation was determined in platelets directly exposed to APAP/NAPQI.

Results: Exposure to APAP decreased platelet aggregation under co-culture conditions but not in platelet-only cultures. Conversely, NAPQI exposure decreased platelet aggregation in both co-culture and platelet-only conditions. Both APAP and NAPQI reduced cell viability in HepG2 and HepG2^E47 cells, with BSO enhancing APAP toxicity, while 4-MP mitigated it. Acetaminophen exposure led to ROS production in HepG2^E47 cells, with no effect of CMZ and 4-MP.

Conclusions: Acetaminophen exposure impacts platelet aggregation in co-cultures of platelets and HepG2/HepG2^E47 cells with increased ROS production in HepG2^E47 cells and 4-MP preventing APAP-induced cytotoxicity in HepG2^E47 cells. While APAP had no direct effect on platelets, NAPQI exposure acted to decrease platelet aggregation. These findings enhance our understanding of the mechanisms of APAP-induced hepatotoxicity and the potential role of APAP-induced hepatocellular toxicity in platelet aggregation.