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Annals of the Rheumatic Diseases May 2023
PubMed: 36261246
DOI: 10.1136/ard-2022-222938 -
Aging and Disease Oct 2020Recent studies have revealed novel forms of cell death beyond the canonical types of cellular apoptosis and necrosis, and these novel forms of cell death are induced by... (Review)
Review
Recent studies have revealed novel forms of cell death beyond the canonical types of cellular apoptosis and necrosis, and these novel forms of cell death are induced by extreme microenvironmental factors. Pyroptosis, a type of regulated cell death, occurs when pattern recognition receptors (PRRs) induce the activation of cysteine-aspartic protease 1 (caspase-1) or caspase-11, which can trigger the release of the pyrogenic cytokines interleukin-1β (IL-1β) and IL-18. Osteoarthritis (OA), the most common joint disease worldwide, is characterized by low-grade inflammation and increased levels of cytokines, including IL-1β and IL-18. Additionally, some damaged chondrocytes associated with OA exhibit morphological changes consistent with pyroptosis, suggesting that this form of regulated cell death may contribute significantly to the pathology of OA. This review summarizes the molecular mechanisms of pyroptosis and shows the critical role of NLRP3 (NLR family, pyrin domain containing 3; NLR refers to "nucleotide-binding domain, leucine-rich repeat") inflammasomes. We also provide evidence describing potential role of pyroptosis in OA, including the relationship with OA risk factors and the contribution to cartilage degradation, synovitis and OA pain.
PubMed: 33014529
DOI: 10.14336/AD.2019.1127 -
Zeitschrift Fur Rheumatologie Jun 2024Fever is a frequent and important symptom in patients with rheumatological diseases and can be an expression of activity of the underlying rheumatological disease.... (Review)
Review
Fever is a frequent and important symptom in patients with rheumatological diseases and can be an expression of activity of the underlying rheumatological disease. There is great variability in the incidence of fever as a symptom of the disease between individual diseases. The growing understanding of the molecular signatures of the diseases can help to explain these discrepancies: A genetic overactivation of potently pyrogenic cytokines is the reason why fever is nearly always present in autoinflammatory syndromes. In contrast, fever is less common in polyarthritis and myositis and mostly limited to severe courses of disease. In the diagnostic work-up of fever, frequent differential diagnoses, such as infections, malignancies, side effects of drugs and hypersensitivity reactions should be considered. This article provides an overview of the physiology of the development of fever, describes the relevance of fever in individual rheumatological diseases and proposes a workflow for the clinical clarification of rheumatological patients who present with fever.
Topics: Humans; Rheumatic Diseases; Fever; Diagnosis, Differential; Fever of Unknown Origin
PubMed: 38634905
DOI: 10.1007/s00393-024-01505-y -
European Journal of Clinical... Jan 2020Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to... (Review)
Review
PURPOSE
Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia.
METHODS
A comprehensive search was performed across 5 databases covering the period of inception to March 2019, for publications that reported hyperthermia associated with drug use. Studies that reported potential drug association with hyperthermia due to altered thermoregulatory mechanisms were included. Case reports of less than 3 cases were excluded, as well as hyperthermia due to other causes, such as hypersensitivity, malignant hyperthermia and neuroleptic malignant syndrome. The primary outcomes of interest were hospitalisation and mortality.
RESULTS
The literature search initially identified a total of 2609 records. Based on full-text analysis, 11 articles met the inclusion criteria, of which there were 5 case-control studies, 2 case series and 4 retrospective analyses. Studies reported heat-related hospitalisations or emergency department presentations associated with the use of psychotropics (antipsychotics, antidepressants and anxiolytics), anticholinergics, antihistamines, diuretics, cardiovascular agents, non-steroidal anti-inflammatory drugs and anticoagulants. Psychotropic drugs were reported to be associated with increased heat-related mortality, other than through neuroleptic malignant syndrome, but findings varied among the studies.
CONCLUSION
Given the relative lack of publications, more research is necessary to study specific effects of drugs on body temperature and the likelihood of inducing non-pyrogenic hyperthermia. In particular, psychotropics, anticholinergics, diuretics and cardiovascular agents are of interest for future studies.
Topics: Anti-Anxiety Agents; Antipsychotic Agents; Body Temperature Regulation; Cholinergic Antagonists; Drug-Related Side Effects and Adverse Reactions; Fever; Humans; Psychotropic Drugs; Retrospective Studies
PubMed: 31642960
DOI: 10.1007/s00228-019-02763-5 -
World Journal of Gastrointestinal... May 2024Gastrointestinal (GI) cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,...
Gastrointestinal (GI) cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality, especially in the colorectum, esophagus, stomach, and liver. Interleukin-1β (IL-1β) is a leukocytic pyrogen recognized as a tumor progression-related cytokine. IL-1β secretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3, inflammasome formation, and activation of IL-1 converting enzyme. Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments, promoting proliferation and metastatic potential of cancer cells and tumorigenesis . The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types. However, as a leukocytic pro-inflammatory cytokine, IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers. This editorial discusses the up-to-date roles of IL-1β in GI cancers, including underlying mechanisms and downstream signaling pathways. Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.
PubMed: 38764841
DOI: 10.4251/wjgo.v16.i5.1676 -
International Journal of Molecular... Apr 2024Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell... (Review)
Review
Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment.
Topics: Humans; Lipopolysaccharides; Obesity; Gastrointestinal Microbiome; Animals; Inflammation
PubMed: 38673890
DOI: 10.3390/ijms25084305 -
Molecules (Basel, Switzerland) Jul 2020Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety... (Review)
Review
Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety profiles. IIMIs are a large family of molecules with diverse compositions and structures that contribute to the immune-mediated adverse effects (IMAE) of drug products. Pyrogenicity (the ability to induce fever) and activation of innate immune responses underlying both acute toxicities (e.g., anaphylactoid reactions or pseudoallergy, cytokine storm) and long-term effects (e.g., immunogenicity) are among the IMAE commonly related to IIMI contamination. Endotoxins of gram-negative bacteria are the best-studied IIMIs in that both methodologies for and pitfalls in their detection and quantification are well established. Additionally, regulatory guidance documents and research papers from laboratories worldwide are available on endotoxins. However, less information is currently known about other IIMIs. Herein, we focus on one such IIMI, namely, beta-glucans, and review literature and discuss the experience of the Nanotechnology Characterization Lab (NCL) with the detection of beta-glucans in nanotechnology-based drug products.
Topics: Drug Compounding; Drug Contamination; Nanotechnology; Pharmaceutical Preparations; beta-Glucans
PubMed: 32722261
DOI: 10.3390/molecules25153367 -
ALTEX 2021Monocyte activation tests (MAT) are widely available but rarely used in place of animal-based pyrogen tests for safety assessment of medical devices. To address this...
Monocyte activation tests (MAT) are widely available but rarely used in place of animal-based pyrogen tests for safety assessment of medical devices. To address this issue, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods and the PETA International Science Consortium Ltd. convened a workshop at the National Institutes of Health on September 18-19, 2018. Participants included representatives from MAT testing laboratories, medical device manufacturers, the U.S. Food and Drug Administration's Center for Devices and Radiologic Health (CDRH), the U.S. Pharmacopeia, the International Organization for Standardization, and experts in the development of MAT protocols. Discussions covered industry experiences with the MAT, remaining challenges, and how CDRH's Medical Device Development Tools (MDDT) Program, which qualifies tools for use in evaluating medical devices to streamline device development and regulatory evaluation, could be a pathway to qualify the use of MAT in place of the rabbit pyrogen test and the limulus amebocyte lysate test for medical device testing. Workshop outcomes and follow-up activities are discussed.
Topics: Animal Testing Alternatives; Animals; Endotoxins; Equipment and Supplies; Monocytes; Pyrogens; Rabbits; Toxicity Tests
PubMed: 33452530
DOI: 10.14573/altex.2012021 -
BioTechniques May 2021Testing of parenteral pharmaceuticals and medical devices for pyrogens (fever-inducing substances) is critical to patient safety. The original rabbit pyrogen test has...
Testing of parenteral pharmaceuticals and medical devices for pyrogens (fever-inducing substances) is critical to patient safety. The original rabbit pyrogen test has largely been replaced by different bacterial endotoxin tests based on amebocyte lysate (LAL), sourced from the blood equivalent of horseshoe crabs after comparative studies to the rabbit pyrogen test. Since 2004 a bacterial endotoxin test based on recombinant factor C (rFC), the endotoxin sensor protein inside of LAL, has been used as an animal-free alternative to LAL. Likewise, numerous studies compared LAL and rFC. Here we describe the history of pyrogen and bacterial endotoxin testing and summarize the evidence presented by those studies. We demonstrate that rFC and LAL are equivalent and comparable.
Topics: Animal Testing Alternatives; Animals; Endotoxins; Horseshoe Crabs; Pyrogens; Rabbits
PubMed: 33956506
DOI: 10.2144/btn-2020-0165 -
Scientific Reports Jul 2022Many medical procedures could benefit from the use of tissue sealants which allow for reduced surgery time, limited blood loss, easier tissue handling, and fewer...
Many medical procedures could benefit from the use of tissue sealants which allow for reduced surgery time, limited blood loss, easier tissue handling, and fewer postoperative complications. The safety and biocompatibility of surgical sealants are of paramount importance therefore, the aim of this study is to investigate the biocompatibility of NE'X Glue Surgical Adhesive. Chemical characterization (VOC and elements), cytotoxicity (MEM elution), genotoxicity (AMES and MLA), endotoxin contamination, sensitization potential, intracutaneous reactivity, acute and subchronic systemic toxicity with implantation as well as pyrogenicity were evaluated to investigate the biocompatibility of the NE'X Glue Surgical Adhesive. Studies were conducted according to ISO 10993 standards. The biocompatibility requirements with accordance to ISO 10993-1 for NE'X Glue were met. In vitro studies showed that NE'X Glue surgical adhesive is non-cytotoxic and non-mutagenic. Also, in vivo studies demonstrated that NE'X Glue shows no signs of toxicity, has no pyrogenic potential, and is non-sensitizing and non-irritating. The chemical characterization showed that no compounds were identified above Analytical Evaluation Threshold (AET), and no elements with concentrations higher than element-specific PDE (µg/day) were detected. NE'X Glue Surgical Adhesive is a versatile and promising new surgical sealant with a wide range of potential applications and very good*0* biocompatibility.
Topics: Albumins; Aldehydes; Humans; Injections; Postoperative Complications; Tissue Adhesives
PubMed: 35882896
DOI: 10.1038/s41598-022-16853-5