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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 -
Clinical Psychopharmacology and... Feb 2021Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of... (Review)
Review
Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of different levels of the neuraxis. Several psychotropic drug classes and combinations have been associated with a classic clinical syndrome of hyperthermia, skeletal muscle hyper-metabolism, rigidity or rhabdomyolysis, autonomic dysfunction and altered mental status ranging from catatonic stupor to coma. It is critical for clinicians to have a high index of suspicion for these relatively uncommon drug-induced adverse effects and to become familiar with their management to prevent serious morbidity and mortality. Although these syndromes look alike, they are triggered by quite different mechanisms, and apart from the need to withdraw or restore potential triggering drugs and provide intensive medical care, specific treatments may vary. Clinical similarities have led to theoretical speculations about common mechanisms and shared genetic predispositions underlying these syndromes, suggesting that there may be a common "thermic stress syndrome" triggered in humans and animal models by a variety of pharmacological or environmental challenges.
PubMed: 33508784
DOI: 10.9758/cpn.2021.19.1.1 -
British Journal of Anaesthesia Aug 2022
Topics: Calcium Channels, L-Type; Czech Republic; Humans; Malignant Hyperthermia; Mutation; Ryanodine Receptor Calcium Release Channel; Slovakia
PubMed: 35718563
DOI: 10.1016/j.bja.2022.04.029 -
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 -
Journal of Clinical Medicine Jun 2023Malignant hyperthermia is a rare but life-threatening pharmacogenetic disorder triggered by exposure to specific anesthetic agents. Although this occurrence could affect... (Review)
Review
Malignant hyperthermia is a rare but life-threatening pharmacogenetic disorder triggered by exposure to specific anesthetic agents. Although this occurrence could affect virtually any patient during the perioperative time, the pediatric population is particularly vulnerable, and it has a five-fold higher incidence in children compared to adults. In the last few decades, synergistic efforts among leading anesthesiology, pediatrics, and neurology associations have produced new evidence concerning the diagnostic pathway, avoiding unnecessary testing and limiting false diagnoses. However, a personalized approach and an effective prevention policy focused on clearly recognizing the high-risk population, defining perioperative trigger-free hospitalization, and rapid activation of supportive therapy should be improved. Based on epidemiological data, many national scientific societies have produced consistent guidelines, but many misconceptions are common among physicians and healthcare workers. This review shall consider all these aspects and summarize the most recent updates.
PubMed: 37373564
DOI: 10.3390/jcm12123869 -
Anesthesiology Dec 2020It is timely to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here the authors pose a simple, but... (Review)
Review
It is timely to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here the authors pose a simple, but bold question: what would it take to end deaths from malignant hyperthermia? The authors review recent advances and propose a scientific and clinical pathway toward this audacious goal to provoke discussion in the field.
Topics: Genetic Predisposition to Disease; Genetic Testing; Genomics; Humans; Malignant Hyperthermia
PubMed: 32898259
DOI: 10.1097/ALN.0000000000003547 -
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 -
Cancers Nov 2021Malignant melanoma frequently develops cutaneous and/or subcutaneous metastases during the course of the disease. These may present as non-nodal locoregional metastases... (Review)
Review
Malignant melanoma frequently develops cutaneous and/or subcutaneous metastases during the course of the disease. These may present as non-nodal locoregional metastases (microsatellite, satellite, or in-transit) included in stage III or as distant metastases in stage IV. Their presentation is heterogeneous and associated with significant morbidity resulting from both disease-related functional damage and treatment side effects. The standard treatment is surgical excision, whereas local therapies or systemic therapies have a role when surgery is not indicated. Radiotherapy can be used in the local management of ITM, subcutaneous relapses, or distant metastases to provide symptom relief and prolong regional disease control. To increase the local response without increasing toxicity, the addition of hyperthermia and intralesional therapies to radiotherapy appear to be very promising. Boron neutron capture therapy, based on nuclear neutron capture and boron isotope fission reaction, could be an alternative to standard treatments, but its use in clinical practice is still limited. The potential benefit of combining radiotherapy with targeted therapies and immunotherapy has yet to be explored in this lesion setting. This review explores the role of radiotherapy in the treatment of cutaneous and subcutaneous lesions, its impact on outcomes, and its association with other treatment modalities.
PubMed: 34831017
DOI: 10.3390/cancers13225859