RESUMO
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.
Assuntos
Epilepsias Mioclônicas , Hipertermia Induzida , Masculino , Humanos , Adulto Jovem , Adulto , Zonisamida/uso terapêutico , Epilepsias Mioclônicas/complicações , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Convulsões/tratamento farmacológico , Convulsões/etiologia , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Ácido Valproico/uso terapêutico , Hipertermia/tratamento farmacológico , Anticonvulsivantes/uso terapêuticoRESUMO
The present study was designed to evaluate the antipyretic and antinociceptive activities of R. communis leaves and W. somnifera roots hydroalcoholic extracts in Wistar rats. To assess the antipyretic activity, Brewer's yeast suspension was used to induce hyperthermia. Antinociceptive activity was observed using acetic acid-induced abdominal writhing, formalin-induced paw licking reflex and heat-induced pain models. R. communis and W. somnifera extracts were used at 150, 250 and 500mg/kg. Results showed that administration of both plants significantly (p<0.001) lowered rectal temperature (°C) in a dose-dependent manner from 1h to 4h of study. R. communis and W. somnifera extracts showed a dose-dependent reduction in abdominal writhing induced by acetic acid and decreased the paw licking reflex in formalin-induced nociceptive response. In the heat test, R. communis and W. somnifera extracts exhibited significant (p<0.001) analgesic effects evidenced as an increase in latency time. However, R. communis exhibited prominent antipyretic and antinociceptive activities at 250 and 500mg/kg as compared to W. somnifera. Conclusively, R. communis and W. somnifera could be a potential source of antipyretic and analgesic agents which require further studies.
Assuntos
Analgésicos/farmacologia , Antipiréticos/farmacologia , Extratos Vegetais/farmacologia , Ricinus/química , Withania/química , Animais , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Hipertermia/induzido quimicamente , Hipertermia/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Raízes de Plantas/química , Ratos , Ratos Wistar , Saccharomyces cerevisiaeRESUMO
With the increasing clinical use of invasive medical devices, various healthcare-associated infections (HAIs) caused by bacterial biofilm colonization of biomedical devices have posed serious threats to patients. The formation of biofilms makes it much more difficult and costly to treat infections. Here, we report a nitric oxide (NO)-releasing gold nanocage (AuNC@NO) that is stimulated by near-infrared (NIR) irradiation to deliver NO and generate hyperthermia for biofilm elimination. AuNC@NO was prepared by immobilizing a temperature-responsive NO donor onto gold nanocages (AuNCs) through thiol-gold interactions. AuNC@NO possesses stable and excellent photothermal conversion efficiency, as well as the characteristics of slow NO release at physiological temperature and on-demand quick NO release under NIR irradiation. Based on these features, AuNC@NO exhibits enhanced in vitro bactericidal and antibiofilm efficacy compared with AuNCs, which could achieve 4 orders of magnitude bacterial reduction and 85.4% biofilm elimination under NIR irradiation. In addition, we constructed an implant biofilm infection model and a subcutaneous biofilm infection model to evaluate the anti-infective effect of AuNC@NO. The in vivo results indicated that after 5 min of 0.5 W cm-2 NIR irradiation, NO release from AuNC@NO was significantly accelerated, which induced the dispersal of methicillin-resistant Staphylococcus aureus (MRSA) biofilms and synergized with photothermal therapy (PTT) to kill planktonic MRSA that had lost its biofilm protection. Meanwhile, the surrounding tissues showed little damage because of controlled photothermal temperature and toxicity. In view of the above-mentioned results, the AuNC@NO nanocomposite developed in this work reveals potential application prospects as a useful antibiofilm agent in the field of biofilm-associated infection treatment.
Assuntos
Antibacterianos/farmacologia , Ouro/farmacologia , Hipertermia/tratamento farmacológico , Nanopartículas Metálicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Óxido Nítrico/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Feminino , Ouro/química , Camundongos , Camundongos Endogâmicos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óxido Nítrico/química , Tamanho da Partícula , Processos Fotoquímicos , Terapia Fototérmica , Propriedades de SuperfícieRESUMO
We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. This class of compounds is designed to carry a payload of a cytotoxic agent and adequately circulate in order to accumulate at a tumor that is being heated. At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Hipertermia Induzida , Hipertermia/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Doxorrubicina/síntese química , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Humanos , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêuticoRESUMO
BACKGROUND: Photothermal therapy (PTT), involving application of localized hyperthermia to kill cancer cells, has attracted wide attention in cancer therapy. The production of reactive oxygen species (ROS) during PTT may cause irreversible damage to healthy tissues around the tumor. Simultaneously, hyperthermia can stimulate inflammatory response, thus promoting tumor recurrence and metastasis. Therefore, it is of paramount importance to reduce the undesired side effects for further development of PTT. RESULTS: Using a hydrothermal method, spherical Prussian blue nanoparticles (PBs) with uniform size were prepared. The PBs exhibited good dispersion and stability in saline with an average hydrodynamic size of 110 nm. The prepared PBs had a high photothermal conversion efficiency and photothermal stability. The PBs showed intrinsic ROS scavenging properties in vitro. Antioxidant and anti-inflammatory effects of PBs were also observed in vivo. Assessment of toxicity and endoplasmic reticulum stress-inducing ability showed that PBs did not induce an inflammatory response. Tissues of major organs of mice stained with hematoxylin-eosin showed no significant damage, indicating good biocompatibility and safety of PBs. CONCLUSION: The designed single-component PBs with intrinsic ROS scavenging and anti-inflammatory properties could avoid inflammatory response and heat stress-induced ROS during PTT. Thus, further research on PBs is worthwhile to achieve their clinical translation and promote the development of PTT.
Assuntos
Ferrocianetos/química , Ferrocianetos/farmacologia , Hipertermia Induzida/métodos , Hipertermia/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Terapia Fototérmica/métodos , Animais , Neoplasias da Mama , Feminino , Hipertermia/patologia , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fármacos Fotossensibilizantes/farmacologia , Células RAW 264.7 , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Hyperthermia is one of the promising cancer treatment strategies enabled by local heating with the use of tumor-targeting magnetic nanoparticles (MNP) under a non-invasive magnetic field. However, one of the remaining challenges is how to achieve therapeutic levels of heat (without causing damages to regular tissues) in tumors that cannot be effectively treated with anti-tumor drug delivery. RESULTS: In this work, we report a facile method to fabricate magnetic nanorods for hyperthermia by one-step wet chemistry synthesis using 3-Aminopropyltrimethoxysilane (APTMS) as the shape-controlling agent and ferric and ferrous ions as precursors. By adjusting the concentration of APTMS, hydrothermal reaction time, ratios of ferric to ferrous ions, magnetic nanorods with aspect ratios ranging from 4.4 to 7.6 have been produced. At the clinically recommended field strength of 300 Oe (or less) and the frequency of 184 kHz, the specific absorption rate (SAR) of these nanorods is approximately 50 % higher than that of commercial Bionized NanoFerrite particles. CONCLUSIONS: This increase in SAR, especially at low field strengths, is crucial for treating deep tumors, such as pancreatic and rectal cancers, by avoiding the generation of harmful eddy current heating in normal tissues.
Assuntos
Antineoplásicos/farmacologia , Hipertermia/tratamento farmacológico , Magnetismo , Nanopartículas/uso terapêutico , Nanotubos/química , Compostos Férricos/uso terapêutico , Calefação , Temperatura Alta , Humanos , Hipertermia Induzida/métodos , Campos Magnéticos , Neoplasias/tratamento farmacológicoRESUMO
ETHNO-PHARMACOLOGICAL RELEVANCE: Artemisia judaica L is an aromatic medicinal plant growing widely in Saint Katherine, Sinai, Egypt, and used in traditional medicine as a herbal remedy for antibacterial, anthelmintic, antidiabetic, analgesic and anti-inflammatory activities. Additionally, other Arabic regions commonly used it in their folk medicines for the treatment of fungal infections, atherosclerosis, cancer, diabetes, arthritis, and inflammatory-related diseases. AIM OF THE STUDY: Based on the traditional medicinal uses of A. judaica, the present study was designed to validate some of the traditional uses as the analgesic, anti-inflammatory, antipyretic, hepatoprotective, antidiabetic, and antioxidant activities of 80% aqueous methanol extract (AME) of A. judaica aerial parts as well as isolation and identification of its flavonoid content. MATERIALS AND METHODS: AME of A. judaica aerial parts was fractionated using column chromatography and the structures of the isolated compounds were established using different spectroscopic data. Analgesic activity was evaluated using acetic acid-induced writhing in mice; antipyretic activity was assessed using yeast suspension-induced hyperthermia in rats; anti-inflammatory activity was evaluated using carrageenan-induced paw edema; the hepatoprotective effect was studied by measuring liver enzymes in carbon tetrachloride(CCl4)-induced hepatotoxicity rats while antidiabetic activity was estimated in alloxan hyperglycemia. RESULTS: Eight flavone compounds namely luteolin 4' methyl ether 7-O-ß-D-4C1-glucopyranoside (1), 8-methoxyapigenin 7-O-ß-D-4C1-galactopyranoside (2), isovitexin (3), 8-methoxyluteolin 7-O-ß-D-4C1-glucopyranoside (4), diosmetin (5), cirsimaritin (6), luteolin (7), and apigenin (8) were identified from AME of A. judaica. The AME was found to be non-toxic to mice up to 5 g/kg b.w. Moreover, it exhibits significant analgesic antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities in a dose-dependent manner. CONCLUSION: The AME was nontoxic; it exhibits significant analgesic, antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities. Moreover, the isolated flavone was identified from AME for the first time.
Assuntos
Artemisia/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antipiréticos/química , Antipiréticos/isolamento & purificação , Antipiréticos/farmacologia , Antipiréticos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Modelos Animais de Doenças , Edema/tratamento farmacológico , Egito , Feminino , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/uso terapêutico , Hipertermia/tratamento farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Medicina Tradicional , Metanol/química , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , RatosRESUMO
To ensure improved efficacy and minimized toxicity of therapeutic molecules, it is generally accepted that specifically delivering them to the subcellular site of their action will be attractive. Phototherapy has received considerable attention because of its noninvasiveness, high temporal-spatial resolution, and minimal drug resistance. As important functional organelles in cells, mitochondria and endoplasmic reticulum (ER) participate in fundamental cellular processes, which make them much more sensitive to reactive oxygen species (ROS) and hyperthermia. Thus, mitochondria- or ER-targeted phototherapy will be rational strategies for synergetic cancer therapy. In this review, we focus on the latest advances in molecules and nanomaterials currently used for mitochondria- and ER-targeted phototherapy.
Assuntos
Materiais Biocompatíveis/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Organelas/química , Fototerapia , Materiais Biocompatíveis/química , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Hipertermia/tratamento farmacológico , Hipertermia/metabolismo , Teste de Materiais , Mitocôndrias/metabolismo , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismoRESUMO
Magnetic fluid hyperthermia has been one clinical treatment method in malignancy on account of the sufficient heat generation, which originates from hysteresis loss of magnetic nanomedicine in alternating magnetic field. Magnetic nanomedicine can also be employed as drug carrier for chemotherapy. Nevertheless few magnetic nanocarries has been approved in clinic, owing to the high pharmaceutical demand. For broadening the clinical application of current magnetic nanomedicine, novel magnetic hydrogel complex (DOX@FMT-MC) constituted by Doxorubicin, Ferumoxytol and Medical Chitosan was produced for hyperthermia and chemo synergistic therapy. The three materials were approved in clinic. Heat induction in vitro and rheology mesurements suggested this complex succeed in transforming into physical hydrogel when reaching hyperthermia temperature in alternating magnetic field. Drug release experiment implied the complex has the temperature-dependent slow drug release behaviour. Cell apoptosis assay presented that DOX@FMT-MC complex gave enhanced synergistic efficacy with 32.4 % on colon carcinoma cell treatment in vitro, compared to other therapeutic groups. Heat induction in mice subcutaneous xenografted tumour demonstrated the better heating performance of the complex than that of DOX@FMT. The novel hydrogel complex incorporated with three clinical available drugs promises the great potential in tumour synergistic treatment, motivating the clinical indication development of magnetic nanomedicine.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Quitosana/farmacologia , Doxorrubicina/farmacologia , Óxido Ferroso-Férrico/farmacologia , Hidrogéis/farmacologia , Hipertermia/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Quitosana/administração & dosagem , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Óxido Ferroso-Férrico/administração & dosagem , Células HT29 , Humanos , Hidrogéis/administração & dosagem , Hipertermia/patologia , Hipertermia Induzida , Injeções Subcutâneas , Campos Magnéticos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg (Sanyeqing) is traditionally used as a folk medicine for the treatments of inflammation, high fever, hepatitis and cancer, and can improve the immune function of the patient. It belongs to the family of Vitaceae, and is mainly distributed in southeast China (Yunnan province) and can be found in India (Andaman Islands), Myanmar, Thailand, Vietnam, Malaysia and Indonesia in the valleys with 1100-1300 m above the sea level. AIM OF THE STUDY: The present study aimed to characterize the chemical properties of a purified polysaccharide extracted from the aerial part of Tetrastigma hemsleyanum (SYQP) and investigate its antipyretic and antitumor effects in mice models. MATERIALS AND METHODS: Water-soluble crude polysaccharides from the aerial parts of Tetrastigma hemsleyanum were extracted and fractionated by DEAE and gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, and FTIR analysis were performed to characterize the SYQP. Antipyretic effect of SYQP was examined using Brewer's yeast induced hyperthermia test. Antitumor effect was investigated using H22 tumor bearing mice. The serum cytokines were determined to evaluated the biological activities of SYQP. RESULTS: SYQP was composed of galacturonic acid (GalA), glucose (Glc), mannose (Man), arabinose (Ara), galactose (Gal), and rhamnose (Rha) with a molar ratio of 11.3:7.1:2.5:1.0:0.9:0.5 and it had an average molecular weight of 66.2 kDa. The oral administration of SYQP at 200 and 400 mg/kg could markedly suppress the hyperthermia of mice induced by Brewer's yeast and decrease the production of cytokines especially prostaglandin E2 (PGE2) in the serum of mice. SYQP inhibited the growth of H22 tumor in mice with inhibitory rate of 39.9% at the administration dose of 200 mg/kg and increased the production of cytokines such as tumor necrosis factor-alpha (TNF-a) and interferon γ (IFN-γ). Experimental results showed that the preventive administration of SYQP before lipopolysaccharide (LPS) reduced the high cytokine levels such as IL-6, IL-10 and IFN-γ, indicating that SYQP might act as a competitor with LPS to interact with toll like receptor 4 (TLR4), which further regulated the secretion of cytokines. CONCLUSION: The anti-inflammatory and antitumor activities of SYQP might be related to its regulation of host immune function by controlling the secretion of cytokines.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Antipiréticos/uso terapêutico , Hipertermia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico , Vitaceae , Animais , Linhagem Celular , Citocinas/sangue , Dinoprostona/sangue , Humanos , Hipertermia/induzido quimicamente , Lipopolissacarídeos , Linfócitos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Componentes Aéreos da Planta , Saccharomyces cerevisiae , Baço/citologia , Carga Tumoral/efeitos dos fármacosRESUMO
Deep vein thrombosis (DVT) is a common and lethal complication of surgery. In the clinic, thrombolytic drugs are primarily used for treating DVT. However, the utilization of thrombolytic drugs is limited due to the risk of urokinase (UK)-related hemorrhagic complications. In this paper, a binary eutectic phase-change fatty acid composed of lauric acid and stearic acid was used to block the pores of gold-mesoporous silica core-shell nanoparticles, so as to deliver thrombolytic drugs. The eutectic mixture has a well-defined melting point at 39.2 °C, which can be used as a biocompatible phase-change material for hyperthermia-triggered drug release. The prepared system presents remarkable photothermal effects due to the gold nanoparticles and quick drug release in response to near-infrared irradiation (NIR). In addition, localized hyperthermia could also enhance the lysis of the thrombus. The thrombolytic effect of this system was evaluated in vitro and in vivo. Herein, a rabbit femoral vein thrombosis model was first built for imitating thrombolysis in vivo. The B-ultrasound was then used to monitor the changes in the thrombus after treatment. The results indicated that the reported system could be potentially used to deliver thrombotic drugs in the clinic.