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Sao Paulo Medical Journal = Revista... 2023Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics...
BACKGROUND
Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out.
CASE REPORT
A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement.
CONCLUSION
Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.
Topics: Female; Humans; Adult; Antipsychotic Agents; Haloperidol; Quetiapine Fumarate; Risperidone; Neuroleptic Malignant Syndrome
PubMed: 38055420
DOI: 10.1590/1516-3180.2022.0401.R1.13032023 -
Journal of Medical Toxicology :... Jul 2023Acetaminophen (APAP) is the most common cause liver injury following alcohol in US patients. Predicting liver injury and subsequent hepatic regeneration in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Acetaminophen (APAP) is the most common cause liver injury following alcohol in US patients. Predicting liver injury and subsequent hepatic regeneration in patients taking therapeutic doses of APAP may be possible using new 'omic methods such as metabolomics and genomics. Multi'omic techniques increase our ability to find new mechanisms of injury and regeneration.
METHODS
We used metabolomic and genomic data from a randomized controlled trial of patients administered 4 g of APAP per day for 14 days or longer with blood samples obtained at 0 (baseline), 4, 7, 10, 13 and 16 days. We used the highest ALT as the clinical outcome to be predicted in our integrated analysis. We used penalized regression to model the relationship between genetic variants and day 0 metabolite level, and then performed a metabolite-wide colocalization scan to associate the genetically regulated component of metabolite expression with ALT elevation. Genome-wide association study (GWAS) analyses were conducted for ALT elevation and metabolite level using linear regression, with age, sex, and the first five principal components included as covariates. Colocalization was tested via a weighted sum test.
RESULTS
Out of the 164 metabolites modeled, 120 met the criteria for predictive accuracy and were retained for genetic analyses. After genomic examination, eight metabolites were found to be under genetic control and predictive of ALT elevation due to therapeutic acetaminophen. The metabolites were: 3-oxalomalate, allantoate, diphosphate, L-carnitine, L-proline, maltose, and ornithine. These genes are important in the tricarboxylic acid cycle (TCA), urea breakdown pathway, glutathione production, mitochondrial energy production, and maltose metabolism.
CONCLUSIONS
This multi'omic approach can be used to integrate metabolomic and genomic data allowing identification of genes that control downstream metabolites. These findings confirm prior work that have identified mitochondrial energy production as critical to APAP induced liver injury and have confirmed our prior work that demonstrate the importance of the urea cycle in therapeutic APAP liver injury.
Topics: Humans; Acetaminophen; Alanine Transaminase; Genome-Wide Association Study; Maltose; Multiomics; Chemical and Drug Induced Liver Injury; Urea
PubMed: 37231244
DOI: 10.1007/s13181-023-00951-5 -
Redox Biology May 2024Acetaminophen (APAP)-induced liver injury is one of the most prevalent causes of acute liver failure (ALF). We assessed the role of the bone morphogenetic protein (BMP)...
Acetaminophen (APAP)-induced liver injury is one of the most prevalent causes of acute liver failure (ALF). We assessed the role of the bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 in APAP-induced hepatotoxicity. The molecular mechanisms that regulate the balance between cell death and survival and the response to oxidative stress induced by APAP was assessed in cultured human hepatocyte-derived (Huh7) cells treated with pharmacological inhibitors of ALK receptors and with modulated expression of ALK2 or ALK3 by lentiviral infection, and in a mouse model of APAP-induced hepatotoxicity. Inhibition of ALK3 signalling with the pharmacological inhibitor DMH2, or by silencing of ALK3, showed a decreased cell death both by necrosis and apoptosis after APAP treatment. Also, upon APAP challenge, ROS generation was ameliorated and, thus, ROS-mediated JNK and P38 MAPK phosphorylation was reduced in ALK3-inhibited cells compared to control cells. These results were also observed in an experimental model of APAP-induced ALF in which post-treatment with DMH2 after APAP administration significantly reduced liver tissue damage, apoptosis and oxidative stress. This study shows the protective effect of ALK3 receptor inhibition against APAP-induced hepatotoxicity. Furthermore, findings obtained from the animal model suggest that BMP signalling might be a new pharmacological target for the treatment of ALF.
Topics: Mice; Animals; Humans; Acetaminophen; Reactive Oxygen Species; Chemical and Drug Induced Liver Injury, Chronic; Liver; Hepatocytes; Oxidative Stress; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Morpholines
PubMed: 38401290
DOI: 10.1016/j.redox.2024.103088 -
Environmental Health Perspectives Aug 2023Childhood lead poisoning remains an important public health issue in the United States, as well as elsewhere in the world. Although primary prevention is a major goal...
BACKGROUND
Childhood lead poisoning remains an important public health issue in the United States, as well as elsewhere in the world. Although primary prevention is a major goal and it is critically important to keep children from getting poisoned, it is also important to explore ways to reduce the neurotoxic effects of lead in those children already poisoned. Whether lead-induced neurotoxicity and its related adverse outcomes are viewed as "permanent" or "persistent" may influence the way in which potential remediation efforts are considered for improving outcomes from childhood lead poisoning.
OBJECTIVES
The objective of this commentary was to discuss the ideas of permanence and persistence in relation to the direct neurotoxic effects of lead on the brain and the resulting adverse outcomes from these effects. Recent new insights regarding potential mitigation of lead-induced neurotoxic effects on brain and behavior are considered along with clinical information on neurorehabilitation to suggest potential strategies for improving cognitive/behavioral outcomes in lead-poisoned children.
DISCUSSION
The distinction between permanent and persistent in regard to lead-induced neurotoxicity and its resulting outcomes may have broad implications for public health policies in response to the problem of childhood lead exposure. The term permanent implies that the damage is irreversible with little chance of improvement. However, there is evidence that at least some of the adverse cognitive/behavioral outcomes from lead exposure are persistent rather than permanent and potentially amenable, under the appropriate circumstances, to some level of mitigation. This author recommends that clinical, interventional research efforts be devoted to exploring optimal neurorehabilitative and enrichment conditions to stimulate plasticity and enhance functioning to determine the extent to which promising results from preclinical studies of lead-induced brain damage and the mitigation of these effects can be successfully translated to humans. https://doi.org/10.1289/EHP12371.
Topics: Child; Humans; Lead; Brain; Lead Poisoning; Neurotoxicity Syndromes; Public Health
PubMed: 37639477
DOI: 10.1289/EHP12371 -
Toxins Jul 2023Exposure to phytotoxins that are present in imported ornamental or native plants is an important cause of animal disease. Factors such as animal behaviors (especially... (Review)
Review
Exposure to phytotoxins that are present in imported ornamental or native plants is an important cause of animal disease. Factors such as animal behaviors (especially indoor pets), climate change, and an increase in the global market for household and ornamental plants led to the appearance of new, previously unreported plant poisonings in Europe. This has resulted in an increase in the incidence of rarely reported intoxications. This review presents some of the emerging and well-established plant species that are responsible for poisoning episodes in companion animals and livestock in Europe. The main plant species are described, and the mechanism of action of the primary active agents and their clinical effects are presented. Data reflecting the real incidence of emerging poisoning cases from plant toxins are scarce to nonexistent in most European countries due to a lack of a centralized reporting/poison control system. The diversity of plant species and phytotoxins, as well as the emerging nature of certain plant poisonings, warrant a continuous update of knowledge by veterinarians and animal owners. The taxonomy and active agents present in these plants should be communicated to ensure awareness of the risks these toxins pose for domestic animals.
Topics: Animals; Plant Poisoning; Animals, Domestic; Europe; Toxins, Biological; Animal Diseases; Poisoning
PubMed: 37505711
DOI: 10.3390/toxins15070442 -
Hepatology Communications Oct 2023Ashwagandha herb is commonly used in Ayurveda and a "fad" dietary supplement for a host of indications based on low levels of evidence. Recently, ashwagandha was... (Review)
Review
BACKGROUND
Ashwagandha herb is commonly used in Ayurveda and a "fad" dietary supplement for a host of indications based on low levels of evidence. Recently, ashwagandha was implicated in multiple reports of herb-induced liver injury (HILI), mainly from the United States. We present the first, and currently largest, series of ashwagandha-HILI from multiple centers in India.
METHODS
We retrospectively analyzed the respective institutional electronic medical records for ashwagandha-HILI. Patients consuming ashwagandha as part of multiherbal formulations or along with other known hepatotoxic supplements or medicines were excluded. All patients underwent a detailed diagnostic workup to exclude competing causes reasonably. Where possible, the implicated herbal formulation was retrieved and subjected to chemical analysis.
RESULTS
Out of 23 patients with liver injury from ashwagandha (January 2019 to December 2022), we report 8 patients with single-ingredient formulation-related HILI. Study cohort was male predominant, and cholestatic hepatitis was the commonest presentation. Five patients had underlying chronic liver disease; 3 presented with acute-on-chronic liver failure, and all 3 died on follow-up. In others, the liver injury was prolonged, nonetheless self-limiting. Liver biopsy revealed cholestatic features predominantly with hepatocellular necrosis and lymphocyte/eosinophil predominant portal-based inflammation. One patient progressed to chronic HILI. Chemical analysis revealed only natural phytochemicals without adulteration or contamination.
CONCLUSIONS
Ashwagandha-HILI presents with cholestatic hepatitis and can lead to the syndrome of acute-on-chronic liver failure with high mortality in those with pre-existing liver disease. Educating the public on avoiding the use of potentially toxic and unrecommended herbal supplements can help mitigate the avoidable liver disease burden in the community.
Topics: Humans; Male; Retrospective Studies; Acute-On-Chronic Liver Failure; Chemical and Drug Induced Liver Injury, Chronic; Chemical and Drug Induced Liver Injury; India; Hepatitis
PubMed: 37756041
DOI: 10.1097/HC9.0000000000000270 -
Annals of African Medicine 2023The rapid onset of life-threatening clinical manifestations in venomous snake bite could be due to an intravenous bite. This article seeks to review and consider the... (Review)
Review
The rapid onset of life-threatening clinical manifestations in venomous snake bite could be due to an intravenous bite. This article seeks to review and consider the clinical implications, pathophysiology, and management of this rare route of snake envenomation broadly by venomous snakes which are little described in the available literature.
Topics: Animals; Humans; Snake Bites; Antivenins; Snakes
PubMed: 37417008
DOI: 10.4103/aam.aam_9_23 -
Science Advances Dec 2023Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked...
Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted the turnover of TOP2 from DNA with or without TOP2 poisons. Additionally, inhibition of proteasome activity enhanced the chromatin binding of RAD54L2, which in turn led to the removal of TOP2 from chromatin. In conclusion, we propose that RAD54L2-mediated TOP2 turnover is critically important for the avoidance of potential TOP2-linked DNA damage under physiological conditions and in response to TOP2 poisons.
Topics: Poisons; DNA Topoisomerases, Type II; DNA Damage; DNA Repair; DNA; Chromatin
PubMed: 38055811
DOI: 10.1126/sciadv.adi6681 -
Italian Journal of Dermatology and... Feb 2024Honeybees are becoming increasingly familiar to the general population due to the growing popularity of backyard and amateur beekeeping. Although bee venom produces...
Honeybees are becoming increasingly familiar to the general population due to the growing popularity of backyard and amateur beekeeping. Although bee venom produces reactions ranging from mild local irritation to life-threatening anaphylaxis, it is also used for life-saving desensitization immunotherapy in those with severe reactions to bee stings. The use of honeybee venom for immunotherapy has increased due to an enhanced interest in natural therapeutics. Recently, honeybee venom has been administered as a successful, safe, and cost-effective treatment for rheumatoid arthritis, back pain, and skin diseases. During the past two decades, studies have tested honeybee venom's efficacy for treating various skin disorders, including atopic dermatitis, wound healing, and psoriasis. We will review bee venom from multiple perspectives, including its medical applications and mechanisms for dermatological pathologies.
Topics: Humans; Bees; Animals; Bee Venoms; Insect Bites and Stings; Apitherapy; Anaphylaxis; Treatment Outcome
PubMed: 37997319
DOI: 10.23736/S2784-8671.23.07683-1 -
Toxins Jul 2023Ciguatera is a major circumtropical poisoning caused by the consumption of marine fish and invertebrates contaminated with ciguatoxins (CTXs): neurotoxins produced by... (Review)
Review
Ciguatera is a major circumtropical poisoning caused by the consumption of marine fish and invertebrates contaminated with ciguatoxins (CTXs): neurotoxins produced by endemic and benthic dinoflagellates which are biotransformed in the fish food-web. We provide a history of ciguatera research conducted over the past 70 years on ciguatoxins from the Pacific Ocean (P-CTXs) and Caribbean Sea (C-CTXs) and describe their main chemical, biochemical, and toxicological properties. Currently, there is no official method for the extraction and quantification of ciguatoxins, regardless their origin, mainly due to limited CTX-certified reference materials. In this review, the extraction and purification procedures of C-CTXs are investigated, considering specific objectives such as isolating reference materials, analysing fish toxin profiles, or ensuring food safety control. Certain in vitro assays may provide sufficient sensitivity to detect C-CTXs at sub-ppb levels in fish, but they do not allow for individual identification of CTXs. Recent advances in analysis using liquid chromatography coupled with low- or high-resolution mass spectrometry provide new opportunities to identify known C-CTXs, to gain structural insights into new analogues, and to quantify C-CTXs. Together, these methods reveal that ciguatera arises from a multiplicity of CTXs, although one major form (C-CTX-1) seems to dominate. However, questions arise regarding the abundance and instability of certain C-CTXs, which are further complicated by the wide array of CTX-producing dinoflagellates and fish vectors. Further research is needed to assess the toxic potential of the new C-CTX and their role in ciguatera fish poisoning. With the identification of C-CTXs in the coastal USA and Eastern Atlantic Ocean, the investigation of ciguatera fish poisoning is now a truly global effort.
Topics: Animals; Ciguatera Poisoning; Ciguatoxins; Public Health; Fishes; Dinoflagellida; Caribbean Region
PubMed: 37505722
DOI: 10.3390/toxins15070453