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1.
J Physiol ; 602(10): 2227-2251, 2024 May.
Article En | MEDLINE | ID: mdl-38690610

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( Q ̇ $\dot Q$ ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q ̇ $\dot Q$ . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single-leg heating; (3) 3 h of two-leg heating; and (4) 2.5 h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q ̇ $\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q ̇ $\dot Q$ through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q ̇ $\dot Q$ ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and Q ̇ $\dot Q$ . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented Q ̇ $\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.


Cardiac Output , Hyperthermia , Humans , Male , Adult , Hyperthermia/physiopathology , Cardiac Output/physiology , Blood Flow Velocity/physiology , Regional Blood Flow/physiology , Fever/physiopathology , Young Adult , Hot Temperature , Hemodynamics
2.
Sci Rep ; 14(1): 10635, 2024 05 09.
Article En | MEDLINE | ID: mdl-38724575

It is well known that hyperthermia greatly impairs neuromuscular function and dynamic balance. However, whether a greater level of hyperthermia could potentially alter the lower limb simulated muscle activation when crossing an obstacle in female participants remains unknown. Therefore we examined the effect of a systematic increase in oral temperature on lower limb simulated muscle activation when crossing an obstacle in female participants. Eighteen female participants were recruited where they underwent a control trial (Con) and two progressive passive heating trials with Δ 1°C and Δ 2°C increase of oral temperature (Toral) using a 45°C water bath. In each trial, we assessed lower limb simulated muscle activation when crossing an obstacle height of 10%, 20%, and 30% of the participant's leg length and toe-off, toe-above-obstacle and heel-strike events were identified and analyzed. In all events, the lower limb simulated muscle activation were greater in Δ2°C than Δ1°C and Con when both leading and trailing limbs crossed the obstacle height of 20% and 30% leg length (all p < 0.001). However, the lower limb simulated muscle activation were not different between Δ1°C and Con across all obstacle heights (p > 0.05). This study concluded that a greater level of hyperthermia resulted in a greater lower limb simulated muscle activation to ensure safety and stability when females cross an obstacle height of 20% leg length or higher.


Muscle, Skeletal , Humans , Female , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Adult , Young Adult , Hyperthermia/physiopathology , Lower Extremity/physiology
3.
Article En | MEDLINE | ID: mdl-38643961

In fish, thermal and hypoxia tolerances may be functionally related, as suggested by the oxygen- and capacity-limited thermal tolerance (OCLTT) concept, which explains performance failure at high temperatures due to limitations in oxygen delivery. In this study the interrelatedness of hyperthermia and hypoxia tolerances in the Nile tilapia (Oreochromis niloticus), and their links to cardiorespiratory traits were examined. Different groups of O. niloticus (n = 51) were subjected to hypoxia and hyperthermia challenges and the O2 tension for aquatic surface respiration (ASR pO2) and critical thermal maximum (CTmax) were assessed as measurement endpoints. Gill filament length, total filament number, ventricle mass, length and width were also measured. Tolerance to hypoxia, as evidenced by ASR pO2 thresholds of the individual fish, was highly variable and varied between 0.26 and 3.39 kPa. ASR events increased more profoundly as O2 tensions decreased below 2 kPa. The CTmax values recorded for the O. niloticus individuals ranged from 43.1 to 44.8 °C (Mean: 44.2 ± 0.4 °C). Remarkably, there was a highly significant correlation between ASR pO2 and CTmax in O. niloticus (r = -0.76, p < 0.0001) with ASR pO2 increasing linearly with decreasing CTmax. There were, however, no discernible relationships between the measured cardiorespiratory properties and hypoxia or hyperthermia tolerances. The strong relationship between hypoxia and hyperthermia tolerances in this study may be related to the ability of the cardiorespiratory system to provide oxygen to respiring tissues under thermal stress, and thus provides some support for the OCLTT concept in this species, at least at the level of the entire organism.


Cichlids , Gills , Hypoxia , Animals , Gills/metabolism , Cichlids/physiology , Hypoxia/physiopathology , Thermotolerance , Oxygen/metabolism , Heart/physiopathology , Heart/physiology , Hyperthermia/physiopathology
4.
ACS Biomater Sci Eng ; 10(5): 2995-3005, 2024 May 13.
Article En | MEDLINE | ID: mdl-38654432

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.


Calcium , Cell Survival , Hyperthermia, Induced , Magnetic Fields , Reactive Oxygen Species , TRPV Cation Channels , Calcium/metabolism , Reactive Oxygen Species/metabolism , TRPV Cation Channels/metabolism , Humans , Hyperthermia, Induced/methods , Temperature , Ferritins/metabolism , Hyperthermia/metabolism
5.
Int J Hyperthermia ; 41(1): 2335201, 2024.
Article En | MEDLINE | ID: mdl-38583875

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.


Adenocarcinoma , Hyperthermia, Induced , Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Humans , Male , Animals , Mice , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Prostatic Neoplasms, Castration-Resistant/metabolism , PC-3 Cells , Reactive Oxygen Species/metabolism , Microwaves , Tumor Suppressor Protein p53/metabolism , Hyperthermia, Induced/methods , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/metabolism , DNA Repair , Apoptosis , Oxidative Stress , Hyperthermia , Adenocarcinoma/radiotherapy , DNA/metabolism , Cell Line, Tumor , Cell Proliferation
6.
Int J Mol Sci ; 25(6)2024 Mar 07.
Article En | MEDLINE | ID: mdl-38542073

Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). The 4T1 cells were orthotopically injected into Balb/C mice, and mEHT was performed on days 9, 12, and 15 after the implantation. DOX, LTLD, or PEGylated liposomal DOX (PLD) were administered for comparison. The tumor size and DOX accumulation in the tumor were measured. The cleaved caspase-3 (cC3) and cell proliferation were evaluated by cC3 or Ki67 immunohistochemistry and Western blot. The LTLD+mEHT combination was more effective at inhibiting tumor growth than the free DOX and PLD, demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the tumor one hour after treatment. Tumor cell damage was associated with cC3 in the damaged area, and with a reduction in Ki67 in the living area. These changes were significantly the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.


Doxorubicin/analogs & derivatives , Hyperthermia, Induced , Neoplasms , Mice , Animals , Liposomes , Ki-67 Antigen , Hyperthermia, Induced/methods , Doxorubicin/pharmacology , Hyperthermia , Cell Line, Tumor , Polyethylene Glycols
7.
J Therm Biol ; 121: 103827, 2024 Apr.
Article En | MEDLINE | ID: mdl-38518416

Exercise is a common trigger of heat-related illness (HRI) events in dogs, accounting for 74% of canine HRI cases treated under primary veterinary care in the United Kingdom. However, few empirical studies have evaluated the effectiveness of differing cooling methods for dogs with exertional hyperthermia or HRI. This study aimed to prospectively evaluate effects of ambient conditions and post-exercise management practices (cooling methods and vehicular confinement) on the post-exercise temperature change of dogs participating in UK canicross events. Canine temperature was recorded at three intervals post-exercise: as close as possible to 0- (immediately post-exercise), 5-, and 15-min post-exercise. Ambient conditions and post-exercise management were recorded for 115 cooling profiles from 52 dogs. In 28/115 (24.4%) profiles, the dog's temperature increased during the first 5-min post-exercise. Overall, 68/115 (59.1%) profiles included passive cooling (stood or walked outside), 35 (30.4%) active cooling (cold-water immersion or application of a cooling coat), and 12 (10.4%) involved no cooling and were immediately housed in vehicles. No dogs developed hypothermia during the study and no adverse effects were observed from any cooling method. In hyperthermic dogs, overall post-exercise body temperature change was significantly negatively associated (i.e. the dogs cooled more) with 0-min post-exercise body temperature (ß = -0.93, p < 0.001), and not being housed in a vehicle (ß = -0.43, p = 0.013). This study provides evidence cold-water immersion (in water at 0.1-15.0 °C) can be used to effectively and safely cool dogs with exertional hyperthermia. Progressive temperature increases in many dogs - even after exercise has terminated - supports the message to "cool first, transport second" when managing dogs with HRI. When transporting dogs post-exercise or with HRI even after active cooling, care should be taken to cool the vehicle before entry and promote air movement around the dog during transport to facilitate ongoing cooling and prevent worsening of hyperthermia during travel.


Hyperthermia , Physical Conditioning, Animal , Dogs , Animals , Male , Hyperthermia/therapy , Hyperthermia/veterinary , Hyperthermia/physiopathology , Dog Diseases/therapy , Dog Diseases/physiopathology , Female , United Kingdom , Body Temperature , Fever/therapy , Fever/veterinary , Fever/physiopathology , Body Temperature Regulation , Sports
8.
Forensic Sci Int ; 358: 111998, 2024 May.
Article En | MEDLINE | ID: mdl-38552403

Pediatric vehicular hyperthermia (PVH) has aroused wide public concern recently. High temperatures in closed vehicles with full sun exposure and no ventilation in summer seriously endanger children's lives. Aiming at this practical problem, this study first took the temperature of child's core body as a standard, and divided the hyperthermia into three stages: un-compensable heating (Tc > 37ºC), heat stroke (Tc > 40ºC) and critical thermal maximum (Tc > 42ºC). On this basis, two weeks of outdoor parking experiments during 10:00-18:00, using an equivalent size dummy were conducted to explore the influence of ambient temperature and solar irradiation on cabin temperature, humidity, and child's core body temperature. According to the experimental results, at an ambient temperature of 32.4ºC, the child in the cabin developed un-compensable heating within 72 min, suffered heat stroke within 129 min, and reached the critical thermal maximum within 151 min. Considering the limitations of the experiment, a numerical study was conducted to analyze the effects of ambient temperature, solar irradiation, and window radiation characteristics on cabin temperature and flow fields comprehensively. Simulation results were in good agreement with the experiments: even at low ambient temperature Ta = 23ºC or weak solar irradiation (ts = 18:00) condition, the temperature in a closed compartment could reach the "hazardous" level. This study can provide guidance for public to increase security and prevention awareness, and promote the development of relevant policies and technologies.


Temperature , Humans , Body Temperature , Child , Humidity , Hot Temperature , Hyperthermia , Heat Stroke , Automobiles , Sunlight
9.
Brain Inj ; 38(8): 652-658, 2024 Jul 02.
Article En | MEDLINE | ID: mdl-38555516

INTRODUCTION: Bromocriptine is a dopamine receptor agonist used for central hyperthermia with limited data. We describe our single-center experience utilizing bromocriptine for central hyperthermia, including the population treated, most common dosing regimens, adverse events, and discontinuation reasons. METHODS: A retrospective study was conducted screening patients who were admitted to intensive care units for acute neurological insults and administered bromocriptine for central hyperthermia between April 2016 and September 2022. Baseline characteristics, disease severity markers, and bromocriptine doses were collected. Body temperatures prior to the first dose of bromocriptine, at the time of dose, and after each dose were recorded. Co-administration of additional hyperthermia management therapies was noted. RESULTS: Thirty patients were included. The most common diagnosis was traumatic brain injury (TBI) (N = 14). The most common reason for discontinuation was resolution of indication (N = 14). Discontinuation due to mild adverse effects occurred in four patients; hepatotoxicity was the most common. There was a paired mean difference of -0.37°C (p = 0.005) between temperatures before and after bromocriptine initiation. CONCLUSION: Bromocriptine is a potential therapy for the management of central hyperthermia in patients with severe acute neurologic insults who have failed other therapies. Bromocriptine was well tolerated and associated with a low incidence of adverse events.


Bromocriptine , Dopamine Agonists , Humans , Bromocriptine/therapeutic use , Male , Female , Retrospective Studies , Middle Aged , Adult , Dopamine Agonists/therapeutic use , Dopamine Agonists/administration & dosage , Aged , Brain Injuries , Hyperthermia/drug therapy , Brain Injuries, Traumatic/complications , Treatment Outcome , Young Adult
10.
J Therm Biol ; 120: 103804, 2024 Feb.
Article En | MEDLINE | ID: mdl-38460451

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.


Bone Neoplasms , Hyperthermia, Induced , Humans , Male , Bone Neoplasms/radiotherapy , Bone Neoplasms/secondary , Hyperthermia/etiology , Pain , Pain Management , Treatment Outcome , Female
11.
ACS Appl Bio Mater ; 7(3): 1569-1578, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38349029

The therapeutic efficacy of bone tumor treatment is primarily limited by inadequate tumor resection, resulting in recurrence and metastasis, as well as the deep location of tumors. Herein, an injectable doxorubicin (DOX)-loaded magnetic alginate hydrogel (DOX@MAH) was developed to evaluate the efficacy of an alternating magnetic field (AMF)-responsive, chemothermal synergistic therapy for multimodality treatment of bone tumors. The prepared hydrogel exhibits a superior drug-loading capacity and a continuous DOX release. This multifunctionality can be attributed to the combined use of DOX for chemotherapy and iron oxide nanoparticle-containing alginate hydrogels as magnetic hyperthermia agents to generate hyperthermia for tumor elimination without the limit on penetration depth. Moreover, the hydrogel can be formed when in contact with the calcium ions, which are abundant in bone tissues; therefore, this hydrogel could perfectly fit the bone defects caused by the surgical removal of the bone tumor tissue, and the hydrogel could tightly attach the surgical margin of the bone to realize a high efficacy residual tumor tissue elimination treated by chemothermal synergistic therapy. The hydrogel demonstrates excellent hyperthermia performance, as evidenced by in vitro cytotoxicity tests on tumor cells. These tests reveal that the combined therapy based on DOX@MAH under AMF significantly induces cell death compared to single magnetic hyperthermia or chemotherapy. In vivo antitumor effects in tumor-bearing mice demonstrate that DOX@MAH injection at the tumor site effectively inhibits tumor growth and leads to tumor necrosis. This work not only establishes an effective DOX@MAH system as a synergistic chemothermal therapy platform for treating bone tumors but also sheds light on the application of alginate to combine calcium ions of the bone to treat bone defect diseases.


Bone Neoplasms , Hyperthermia, Induced , Animals , Mice , Hydrogels/pharmacology , Calcium , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Bone Neoplasms/drug therapy , Hyperthermia , Hyperthermia, Induced/methods , Alginates , Ions , Magnetic Phenomena
12.
Biomaterials ; 307: 122511, 2024 Jun.
Article En | MEDLINE | ID: mdl-38401482

Combination of different therapies is an attractive approach for cancer therapy. However, it is a challenge to synchronize different therapies for maximization of therapeutic effects. In this work, a smart composite scaffold that could synchronize magnetic hyperthermia and chemotherapy was prepared by hybridization of magnetic Fe3O4 nanoparticles and doxorubicin (Dox)-loaded thermosensitive liposomes with biodegradable polymers. Irradiation of alternating magnetic field (AMF) could not only increase the scaffold temperature for magnetic hyperthermia but also trigger the release of Dox for chemotherapy. The two functions of magnetic hyperthermia and chemotherapy were synchronized by switching AMF on and off. The synergistic anticancer effects of the composite scaffold were confirmed by in vitro cell culture and in vivo animal experiments. The composite scaffold could efficiently eliminate breast cancer cells under AMF irradiation. Moreover, the scaffold could support proliferation and adipogenic differentiation of mesenchymal stem cells for adipose tissue reconstruction after anticancer treatment. In vivo regeneration experiments showed that the composite scaffolds could effectively maintain their structural integrity and facilitate the infiltration and proliferation of normal cells within the scaffolds. The composite scaffold possesses multi-functions and is attractive as a novel platform for efficient breast cancer therapy.


Doxorubicin/analogs & derivatives , Hyperthermia, Induced , Neoplasms , Animals , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Hyperthermia , Magnetic Phenomena , Polyethylene Glycols
13.
ACS Appl Mater Interfaces ; 16(8): 9968-9979, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38358298

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.


Hyperthermia, Induced , Neoplasms , Nitrites , Transition Elements , Humans , Glucose Oxidase , Hydrogen Peroxide , Titanium/pharmacology , Hyperthermia , Neoplasms/therapy , Glucose , Hypoxia , Tumor Microenvironment , Cell Line, Tumor
14.
Leg Med (Tokyo) ; 68: 102418, 2024 May.
Article En | MEDLINE | ID: mdl-38335833

INTRODUCTION: The research aimed to determine individual variations in different core temperature measurements before the experiment, after submersion, after 20 min of exposure for heat stroke. METHODS: Rats were divided into three groups depending on the temperature and length of exposure to water: CG, G41-20 and G41-UD. The protocol was made according to the earlier described methodology of heat shock induction. RESULTS: A significant difference was observed in the G41-UD group; p < 0.0005. The lowest body temperature of the rats was observed, from normothermia, and the highest temperature after death, 37.87 ± 0.62 °C vs 41.20 ± 0.76 °C, the difference between all three groups is p < 0.0005. CONCLUSION: Exposure of Wistar rats to water temperatures in the CG and G41 groups led to a significant change in core temperature. In the control group, the thermoregulatory mechanism firmly established normothermia, while hyperthermia was revealed in the G41 group during the 20-minute exposure.


Body Temperature , Rats, Wistar , Animals , Rats , Male , Hyperthermia , Fever , Heat Stroke , Body Temperature Regulation/physiology
15.
Int J Hyperthermia ; 41(1): 2316085, 2024.
Article En | MEDLINE | ID: mdl-38346911

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.


Doxorubicin/analogs & derivatives , Hyperthermia, Induced , Urinary Bladder Neoplasms , Humans , Gemcitabine , Janus Kinases/therapeutic use , Ki-67 Antigen , STAT Transcription Factors/therapeutic use , Signal Transduction , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Hyperthermia , Hyperthermia, Induced/methods , Organoids/pathology
16.
J Med Case Rep ; 18(1): 3, 2024 Jan 03.
Article En | MEDLINE | ID: mdl-38167335

BACKGROUND: Dravet syndrome is a severe epilepsy disorder characterized by drug-resistant seizures and cognitive dysfunction, often caused by SCN1A gene mutations. It leads to neurodevelopmental delays and motor, behavioral, and cognitive impairments, with a high mortality rate. Treatment options include sodium valproate, clobazam, and newer agents such as cannabidiol and fenfluramine. Zonisamide, which is used in some cases, can cause hyperthermia and oligohydrosis. Herein, we present a case of a patient with Dravet syndrome whose seizures were controlled by treating infections and switching from zonisamide to perampanel. CASE PRESENTATION: A 24-year-old Japanese man with Dravet syndrome presented to our department with aspiration pneumonia. The patient had been treated with valproate, sodium bromide, and zonisamide for a long time. His seizures were triggered by hyperthermia. The patient was experiencing a sustained pattern of hyperthermia caused by infection, zonisamide, and persistent convulsions, which caused a vicious cycle of further seizures. In this case, the control of infection and switching from zonisamide to perampanel improved seizure frequency. CONCLUSION: Dravet syndrome usually begins with generalized clonic seizures in its infancy because of fever and progresses to various seizure types, often triggered by fever or seizure-induced heat due to mutations in the SCN1A gene that increases neuronal excitability. Seizures usually diminish with age, but the heat sensitivity remains. In this case, seizures were increased by repeated infections, and hyperthermia was induced by zonisamide, resulting in status epilepticus. Perampanel, an aminomethylphosphonic acid receptor antagonist, decreased seizures but caused psychiatric symptoms. It was effective in suppressing seizures of Dravet syndrome in this patient.


Epilepsies, Myoclonic , Hyperthermia, Induced , Male , Humans , Young Adult , Adult , Zonisamide/therapeutic use , Epilepsies, Myoclonic/complications , Epilepsies, Myoclonic/drug therapy , Epilepsies, Myoclonic/genetics , Seizures/drug therapy , Seizures/etiology , NAV1.1 Voltage-Gated Sodium Channel/genetics , Valproic Acid/therapeutic use , Hyperthermia/drug therapy , Anticonvulsants/therapeutic use
17.
J Mater Chem B ; 12(5): 1307-1316, 2024 Jan 31.
Article En | MEDLINE | ID: mdl-38226460

Bacterial infection is a key factor affecting wound healing. Conventional treatments might lead to the widespread emergence of drug-resistant bacteria due to the long-term and excessive use of antibiotics. It is necessary to develop an antibiotic-free method for effective treatment of bacterial wound infections. In this work, we constructed an antibiotic-free polysaccharide-based hydrogel dressing (ATB) with near-infrared light-actuated on-demand botanicals release and hyperthermia for the synergistic treatment of wound infections. The ATB hydrogel dressing was made up of agarose as a support matrix, berberine hydrochloride as the active botanicals and TA-Fe(III) nanoparticles as NIR laser-activated photothermal reagents. The ATB hydrogel dressing showed spatiotemporal botanicals release and excellent photothermal properties with NIR irradiation. With the results of in vitro and in vivo antibacterial experiments, the antibiotic-free ATB hydrogel could synergistically eliminate bacteria and accelerate wound healing. Overall, the near-infrared light-responsive ATB hydrogel could provide a promising antibiotic-free strategy for the treatment of bacterial wound infections.


Hyperthermia, Induced , Wound Infection , Humans , Hydrogels/pharmacology , Ferric Compounds , Hyperthermia , Polysaccharides/pharmacology , Infrared Rays , Bandages , Anti-Bacterial Agents/pharmacology , Wound Infection/drug therapy
18.
Pediatr Res ; 95(6): 1448-1454, 2024 May.
Article En | MEDLINE | ID: mdl-38253875

Abnormal temperature in preterm infants is associated with increased morbidity and mortality. Infants born prematurely are at risk of abnormal temperature immediately after birth in the delivery room (DR). The World Health Organization (WHO) recommends that the temperature of newly born infants is maintained between 36.5-37.5oC after birth. When caring for very preterm infants, the International Liaison Committee on Resuscitation (ILCOR) recommends using a combination of interventions to prevent heat loss. While hypothermia remains prevalent, efforts to prevent it have increased the incidence of hyperthermia, which may also be harmful. Delayed cord clamping (DCC) for preterm infants has been recommended by ILCOR since 2015. Little is known about the effect of timing of DCC on temperature, nor have there been specific recommendations for thermal care before DCC. This review article focuses on the current evidence and recommendations for thermal care in the DR, and considers thermoregulation in the context of emerging interventions and future research directions. IMPACT: Abnormal temperature is common amongst very preterm infants after birth, and is an independent risk factor for mortality. The current guidelines recommend a combination of interventions to prevent heat loss after birth. Despite this, abnormal temperature is still a problem, across all climates and economies. New and emerging delivery room practice (i.e., delayed cord clamping, mobile resuscitation trolleys, early skin to skin care) may have an effect on infant temperature. This article reviews the current evidence and recommendations, and considers future research directions.


Body Temperature Regulation , Delivery Rooms , Hypothermia , Infant, Premature , Humans , Infant, Newborn , Hypothermia/prevention & control , Umbilical Cord , Risk Factors , Infant, Extremely Premature , Hyperthermia
20.
Rinsho Shinkeigaku ; 64(1): 17-22, 2024 Jan 20.
Article Ja | MEDLINE | ID: mdl-38092414

A 70-year-old male who has medical history of Parkinson's disease for 26 years admitted to our hospital for trial of levodopa carbidopa intestinal gel (LCIG) therapy because of severe dyskinesia and frequent wearing-off. He developed deterioration when he was treated with one of the levodopa (LD) decacrboxylase inhibitor compounds in the past. Five days after LD had changed into equivalent dose of LD/carbidopa (CD), high fever with hyperCKemia appeared. He was diagnosed as having Parkinsonism-hyperpyrexia syndrome (PHS). Exchange of LD/CD to LD drugs improved the symptoms quickly. Four days after LCIG administration, PHS reappeared. Simultaneously, the patient developed sepsis and disseminated intravascular coagulation (DIC). Thrombocytopenia did not improve after recovery from infection and DIC. Anti-PA IgG and drug-induced lymphocyte stimulation test (DLST) against LCIG showed positive. Exchange of LCIG to LD drugs and intravenous methylprednisolone administration improved the symptoms and thrombocytopenia. CD induced type II and type IV allergy were suspected. This case offers a caution that physicians should be aware of drug allergy in cases of which unexpected symptoms occurred in altering one LD compound to another.


Hypersensitivity , Parkinson Disease , Thrombocytopenia , Male , Humans , Aged , Carbidopa , Levodopa , Antiparkinson Agents/adverse effects , Hyperthermia/drug therapy , Lymphocyte Activation , Parkinson Disease/drug therapy , Hypersensitivity/drug therapy , Drug Combinations , Syndrome
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