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British Journal of Anaesthesia Jul 2023The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who...
The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who have a personal or family history consistent with malignant hyperthermia under anaesthesia and are subsequently demonstrated through diagnostic testing to be at risk.
Topics: Humans; Malignant Hyperthermia; Halothane; Caffeine; Anesthesia; Biopsy
PubMed: 37198032
DOI: 10.1016/j.bja.2023.04.014 -
Clinical Genetics Mar 2024Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early... (Review)
Review
Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.
Topics: Humans; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel; Risk Factors; Risk Assessment
PubMed: 38148504
DOI: 10.1111/cge.14475 -
Journal of Biochemistry Jul 2023Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious... (Review)
Review
Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious consequences can arise due to the unwanted but unavoidable responses of biological systems to heat. This review aims to present a range of responses to heat in biological systems across various spatial scales. We begin by examining the impaired thermogenesis of malignant hyperthermia in model mice and skeletal muscle cells, demonstrating that the progression of this disease is caused by a positive feedback loop between thermally driven Ca2+ signaling and thermogenesis at the subcellular scale. After we explore thermally driven force generation in both muscle and non-muscle cells, we illustrate how in vitro assays using purified proteins can reveal the heat-responsive properties of proteins and protein assemblies. Building on these experimental findings, we propose the concept of 'trans-scale thermal signaling'.
Topics: Animals; Mice; Ryanodine Receptor Calcium Release Channel; Malignant Hyperthermia; Calcium; Muscle, Skeletal
PubMed: 37461189
DOI: 10.1093/jb/mvad053 -
Anesthesia and Pain Medicine Jul 2023Dantrolene sodium (DS) was first introduced as an oral antispasmodic drug. However, in 1975, DS was demonstrated to be effective for managing malignant hyperthermia (MH)... (Review)
Review
Dantrolene sodium (DS) was first introduced as an oral antispasmodic drug. However, in 1975, DS was demonstrated to be effective for managing malignant hyperthermia (MH) and was adopted as the primary therapeutic drug after intravenous administration. However, it is difficult to administer DS intravenously to manage MH. MH is life-threatening, pharmacogenomically related, and induced by depolarizing neuromuscular blocking agents or inhalational anesthetics. All anesthesiologists should know the pharmacology of DS. DS suppresses Ca2+ release from ryanodine receptors (RyRs). RyRs are expressed in various tissues, although their distribution differs among subtypes. The anatomical and physiological functions of RyRs have also been demonstrated as effective therapeutic drugs for cardiac arrhythmias, Alzheimer's disease, and other RyR-related diseases. Recently, a new formulation was introduced that enhanced the hydrophilicity of the lipophilic DS. The authors summarize the pharmacological properties of DS and comment on its indications, contraindications, adverse effects, and interactions with other drugs by reviewing reference articles.
PubMed: 37691593
DOI: 10.17085/apm.22260 -
Nature Communications Aug 2023Nanoparticle-based drug delivery systems have gained much attention in the treatment of various malignant tumors during the past decades. However, limited tumor...
Nanoparticle-based drug delivery systems have gained much attention in the treatment of various malignant tumors during the past decades. However, limited tumor penetration of nanodrugs remains a significant hurdle for effective tumor therapy due to the existing biological barriers of tumoral microenvironment. Inspired by bubble machines, here we report the successful fabrication of biomimetic nanodevices capable of in-situ secreting cell-membrane-derived nanovesicles with smaller sizes under near infrared (NIR) laser irradiation for synergistic photothermal/photodynamic therapy. Porous Au nanocages (AuNC) are loaded with phase transitable perfluorohexane (PFO) and hemoglobin (Hb), followed by oxygen pre-saturation and indocyanine green (ICG) anchored 4T1 tumor cell membrane camouflage. Upon slight laser treatment, the loaded PFO undergoes phase transition due to surface plasmon resonance effect produced by AuNC framework, thus inducing the budding of outer cell membrane coating into small-scale nanovesicles based on the pore size of AuNC. Therefore, the hyperthermia-triggered generation of nanovesicles with smaller size, sufficient oxygen supply and anchored ICG results in enhanced tumor penetration for further self-sufficient oxygen-augmented photodynamic therapy and photothermal therapy. The as-developed biomimetic bubble nanomachines with temperature responsiveness show great promise as a potential nanoplatform for cancer treatment.
Topics: Biomimetics; Hyperthermia, Induced; Photochemotherapy; Phototherapy; Indocyanine Green; Oxygen; Nanoparticles; Cell Line, Tumor
PubMed: 37567901
DOI: 10.1038/s41467-023-40474-9 -
Biomedical Materials (Bristol, England) Aug 2023Glioblastoma (GBM) is the most aggressive and lethal malignant brain tumor, and it is challenging to cure with surgery and treatment. The prevention of permanent brain... (Review)
Review
Glioblastoma (GBM) is the most aggressive and lethal malignant brain tumor, and it is challenging to cure with surgery and treatment. The prevention of permanent brain damage and tumor invasion, which is the ultimate cause of recurrence, are major obstacles in GBM treatment. Besides, emerging treatment modalities and newer genetic findings are helping to understand and manage GBM in patients. Accordingly, researchers are focusing on advanced nanomaterials-based strategies for tackling the various problems associated with GBM. In this context, researchers explored novel strategies with various alternative treatment approaches such as early detection techniques and theranostics approaches. In this review, we have emphasized the recent advancement of GBM cellular models and their roles in designing GBM therapeutics. We have added a special emphasis on the novel genetic and drug target findings as well as strategies for early detection. Besides, we have discussed various theranostic approaches such as hyperthermia therapy, phototherapy and image-guided therapy. Approaches utilized for targeted drug delivery to the GBM were also discussed. This article also describes the recentandadvances using innovative theranostic approaches.
Topics: Humans; Precision Medicine; Glioblastoma; Hyperthermia, Induced; Phototherapy; Drug Delivery Systems
PubMed: 37582381
DOI: 10.1088/1748-605X/acf0ab -
Neuromuscular Disorders : NMD Oct 2023Mutations in RYR1 encoding the ryanodine receptor (RyR) skeletal muscle isoform (RyR1) are a common cause of inherited neuromuscular disorders. Despite its expression in...
Mutations in RYR1 encoding the ryanodine receptor (RyR) skeletal muscle isoform (RyR1) are a common cause of inherited neuromuscular disorders. Despite its expression in a wide range of tissues, non-skeletal muscle manifestations associated with RYR1 mutations have only been rarely reported. Here, we report three patients with a diagnosis of Central Core Disease (CCD), King-Denborough Syndrome (KDS) and Malignant Hyperthermia Susceptibility (MHS), respectively, who in addition to their (putative) RYR1-related disorder also developed symptoms and signs of acute pancreatitis. In two patients, episodes were recurrent, with severe multisystem involvement and sequelae. RyR1-mediated calcium signalling plays an important role in normal pancreatic function but has also been critically implicated in the pathophysiology of acute pancreatitis, particularly in bile acid- and ethanol-induced forms. Findings from relevant animal models indicate that pancreatic damage in these conditions may be ameliorated through administration of the specific RyR1 antagonist dantrolene and other compounds modifying pancreatic metabolism including calcium signalling. These observations suggest that patients with RYR1 gain-of-function variants may be at increased risk of developing acute pancreatitis, a condition which should therefore be considered in the health surveillance of such individuals.
Topics: Animals; Humans; Acute Disease; Calcium; Malignant Hyperthermia; Mutation; Pancreatitis; Ryanodine Receptor Calcium Release Channel
PubMed: 37783627
DOI: 10.1016/j.nmd.2023.09.003