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1.
Exp Anim ; 70(3): 412-418, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-33952794

RESUMO

The mouse bioassay for diarrhetic shellfish poisoning (DSP) toxins had been used as the official method in Japan and also used in the world. In this study, hypothermia, one of the symptoms observed in mice after inoculation with DSP toxins, were characterized. Lethal and sublethal doses of okadaic acid (OA), a representative component of DSP toxins, were inoculated intraperitoneally into mice. Body-temperature changes over time were measured by an electronic thermometer or monitored by an infrared camera. Drastic hypothermia (<30°C in some mice) was observed in a few hours after administration of a lethal dose of OA. Dose-dependency was clearly seen between doses of OA inoculated and body-temperature decrease. Drastic hypothermia was also detected by using an infrared camera. These results suggest that hypothermia could be used as an index for the humane endpoint in experimental animal toxicological studies.


Assuntos
Hipotermia/induzido quimicamente , Toxinas Marinhas/efeitos adversos , Ácido Okadáico/efeitos adversos , Intoxicação por Frutos do Mar/diagnóstico , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Organismos Livres de Patógenos Específicos
2.
Nat Commun ; 12(1): 2648, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976193

RESUMO

The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1-the chemosensor for 2MT. Here we report that Trpa1-/- mice show diminished 2MT-evoked c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel) and nucleus of the solitary tract (NTS). Whereas tetanus toxin light chain-mediated inactivation of NTS-projecting PSTh neurons suppress, optogenetic activation of direct PSTh-rostral NTS pathway induces hypothermia and tail vasodilation. Furthermore, selective opto-stimulation of 2MT-activated, PSTh-projecting PBel neurons by capturing activated neuronal ensembles (CANE) causes hypothermia. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel or PSTh, or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail vasodilation. These studies identify PSTh as a major thermoregulatory hub that connects PBel to NTS to mediate 2MT-evoked innate fear-associated hypothermia and tail vasodilation.


Assuntos
Medo/fisiologia , Hipotermia/metabolismo , Núcleo Solitário/metabolismo , Núcleo Subtalâmico/metabolismo , Canal de Cátion TRPA1/metabolismo , Animais , Regulação da Temperatura Corporal/fisiologia , Medo/psicologia , Hipotermia/induzido quimicamente , Hipotermia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Optogenética/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Canal de Cátion TRPA1/genética , Tiazóis , Vasodilatação/fisiologia
3.
J Physiol Sci ; 71(1): 10, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784982

RESUMO

The aim of the present study was to establish a novel method for inducing deep hypothermia in rats. Cooling rats anesthetized with isoflurane caused a time-dependent decrease in rectal temperature, but cardiac arrest occurred before their body temperature reached 20 °C when isoflurane inhalation was continued during the cooling process. Stopping inhalation of isoflurane when the rectal temperature reached 22.5 °C successfully induced deep hypothermia, although stopping the inhalation at 27.5 °C resulted in spontaneous recovery of rectal temperature. The hypothermic condition was able to be maintained for up to 6 h. A large number of c-Fos-positive cells were detected in the hypothalamus during hypothermia. Both the maintenance of and recovery from hypothermia caused organ injury, but the damage was transient and recovered within 1 week. These findings indicate that the established procedure is appropriate for inducing deep hypothermia without accompanying serious organ injury in rats.


Assuntos
Anestésicos Inalatórios/farmacologia , Temperatura Baixa , Hipotermia/induzido quimicamente , Isoflurano/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Frequência Cardíaca , Hexametônio/farmacologia , Masculino , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley
4.
Life Sci Space Res (Amst) ; 28: 18-21, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33612175

RESUMO

The maintenance of pharmacological torpor and hypothermia (body temperature 28 °C - 33 °C) in rats for a week is presented. For this purpose, our laboratory has developed a device (BioFeedback-2) for the feed-back controlled multiple injections of small doses of a pharmacological composition that we created earlier. On the 7th day, the rat spontaneously come out of the pharmacological torpor, the body temperature returned to normal, and on the 8th day, the animal could consume food and water. The proposed approach for maintaining multi-day pharmacological torpor can be applied in medicine, as well as for protecting astronauts during long missions in space.


Assuntos
Hipotermia/induzido quimicamente , Torpor/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Difenidramina/administração & dosagem , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Retroalimentação , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Ivabradina/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Masculino , Fenotiazinas/administração & dosagem , Propranolol/administração & dosagem , Propiltiouracila/administração & dosagem , Ratos Wistar , Reserpina/administração & dosagem , Serotonina/administração & dosagem , Telemetria/veterinária
5.
Pharmacol Biochem Behav ; 202: 173116, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33493547

RESUMO

Advances in drug vapor exposure systems have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; and 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Sprague Dawley and Wistar rats (N = 22, 5-6/sex per group) received THC via passive vapor exposure (200 mg/mL; 5 conditions) and IP injection (1-20 mg/kg) in a within subject design. The effects of vaped and injected THC on appetite was determined using progressive ratio responding for food pellets. THC effects on nociception, measured using the tail withdrawal assay, and body temperature were also assessed during a 5-h test period for evaluation of time course of effects. Plasma THC concentrations were assessed after THC vapor and 10 mg/kg IP THC. THC vapor produced exposure-related increases and decreases in motivation to obtain food under the progressive ratio schedule. IP THC (3-20 mg/kg) reduced breakpoints. Vaped and injected THC produced exposure and dose-dependent antinociception and hypothermia. Sex and strain differences in THC effects were also observed. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL), but magnitude of behavioral effects were comparable. THC vapor exposure produced reliable, dose orderly effects on food-maintained behavior, nociception, and body temperature that are comparable to effects of IP THC, although there were differences in the time course of behavioral outcomes.


Assuntos
Analgésicos/administração & dosagem , Apetite/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Dronabinol/administração & dosagem , Hipotermia/induzido quimicamente , Nociceptividade/efeitos dos fármacos , Administração por Inalação , Analgésicos/sangue , Analgésicos/química , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Dronabinol/sangue , Dronabinol/química , Feminino , Injeções Intraperitoneais , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Fatores Sexuais , Volatilização
6.
Exp Clin Psychopharmacol ; 29(1): 1-13, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32297788

RESUMO

An inhalation system based on e-cigarette technology produces hypothermic and antinociceptive effects of Δ9-tetrahydrocannabinol (THC) in rats. Indirect comparison of some prior investigations suggested differential impact of inhaled THC between Wistar (WI) and Sprague-Dawley (SD) rats; thus, this study was conducted to directly compare the strains across inhaled and injected routes of administration. Groups (N = 8 per strain) of age-matched male SD and WI rats were prepared with radiotelemetry devices to measure temperature and then exposed to vapor from the propylene glycol (PG) vehicle or THC (25-200 mg/mL of PG) for 30 or 40 min. Additional studies evaluated effects of THC inhalation on plasma THC (50-200 mg/mL) and nociception (100-200 mg/mL) as well as the thermoregulatory effect of intraperitoneal injection of THC (5-30 mg/kg). Hypothermic effects of THC were more pronounced in SD rats, where plasma levels of THC were identical across strains, under either fixed inhalation conditions or injection of a mg/kg equivalent dose. Strain differences in hypothermia were largest after i.p. injection of THC, with SD rats exhibiting dose-dependent temperature reduction after 5 or 10 mg/kg, i.p. and the WI rats only exhibiting significant hypothermia after 20 mg/kg, i.p. The antinociceptive effects of inhaled THC (100, 200 mg/mL) did not differ significantly across the strains. These studies confirm an insensitivity of WI rats, compared with SD rats, to hypothermia induced by THC following inhalation conditions that produced identical plasma THC and antinociception. Thus, quantitative, albeit not qualitative, strain differences may be obtained when studying thermoregulatory effects of THC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Dronabinol/administração & dosagem , Sistemas Eletrônicos de Liberação de Nicotina , Alucinógenos/administração & dosagem , Hipotermia/induzido quimicamente , Locomoção/efeitos dos fármacos , Administração por Inalação , Animais , Regulação da Temperatura Corporal/fisiologia , Dronabinol/toxicidade , Alucinógenos/toxicidade , Hipotermia/fisiopatologia , Injeções Intraperitoneais , Locomoção/fisiologia , Masculino , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Especificidade da Espécie
8.
Korean J Anesthesiol ; 74(1): 53-58, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32498491

RESUMO

BACKGROUND: Interscalene brachial plexus block (ISBPB) is commonly used with general anesthesia for postoperative pain management in shoulder surgery. This study investigated the incidence of hypothermia and changes in the body temperature in patients undergoing arthroscopic shoulder surgery under ISBPB with propofol sedation. METHODS: This retrospective study enrolled 220 patients who underwent arthroscopic shoulder surgery. Patients were divided into general anesthesia (n = 34) and ISBPB with propofol sedation (n = 186) groups, and medical records were retrospectively compared. In addition, patients from the ISBPB group were further divided according to age (elderly, [≥ 65 years]; n = 98 vs. young, [< 65 years]; n = 88), and the incidence of hypothermia and changes in the body temperature were compared. RESULTS: Twenty-seven patients (12.3%) experienced perioperative hypothermia (range; 35.3-35.9℃). The incidence of perioperative hypothermia was 29.4% and 9.1% in the general anesthesia and ISBPB groups, respectively, and there was a significant difference between the two groups (P = 0.002). The incidence of perioperative hypothermia according to age in the ISBPB group was 9.2% and 9.1% in the elderly and young groups, respectively, and there was no significant difference between the two groups (P = 0.983). CONCLUSIONS: The incidence of perioperative hypothermia during arthroscopic shoulder surgery under ISBPB with propofol sedation is lower than that under general anesthesia. Furthermore, when using ISBPB with propofol sedation, the incidence of perioperative hypothermia in elderly patients is similar to that in younger patients.


Assuntos
Bloqueio do Plexo Braquial , Hipotermia , Propofol , Idoso , Anestesia Geral/efeitos adversos , Bloqueio do Plexo Braquial/efeitos adversos , Humanos , Hipotermia/induzido quimicamente , Hipotermia/epidemiologia , Hipotermia/prevenção & controle , Propofol/efeitos adversos , Estudos Retrospectivos , Ombro/cirurgia
9.
J Integr Neurosci ; 19(4): 619-628, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33378836

RESUMO

Therapeutic strategies for traumatic spinal cord injury generally involve rectifying concomitant destruction to the spinal cord from inflammation, mitochondrial dysfunction, and eventual neuronal apoptosis. Elevating the expression of spinal cord injury-attenuated CDGSH iron-sulfur domain-2 has been shown to mitigate the pathologies above. In the current work, hypothermia was induced via continuous cryogen spray cooling in a rat spinal cord hemisection model. Spinal cord injury was shown to elevate the mRNA expression of proinflammatory mediators, including NFκB, iNOS, TNF-α, and regulated upon activation, normal T-cell expressed and secreted as well as lower CDGSH iron-sulfur domain-2 expression. Cryogen spray cooling treatment was shown to attenuate inflammatory reactions and elevate CDGSH iron-sulfur domain-2 expression. Immunohistochemical analysis of the glial fibrillary acidic protein, caspase-3 and NeuN in spinal cord injured rats that underwent cryogen spray cooling treatment revealed notable reductions in injury-induced astrocytic activation, apoptosis, neuronal loss, and decline in CDGSH iron-sulfur domain-2 expression. These results demonstrate the CDGSH iron-sulfur domain-2 preserving effects of cryogen spray cooling, which could contribute to the prevention of astrocytic activation, astrocyte-mediated neuroinflammation, apoptosis, and neuron loss.


Assuntos
Apoptose , Astrócitos , Hipotermia Induzida , Hipotermia/induzido quimicamente , Inflamação , Proteínas de Membrana/metabolismo , Traumatismos da Medula Espinal , Animais , Apoptose/fisiologia , Astrócitos/imunologia , Astrócitos/metabolismo , Astrócitos/patologia , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/terapia , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia
10.
J Vet Med Sci ; 82(12): 1757-1762, 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33055454

RESUMO

Hypothermia during anesthetic events is a common adverse effect of anesthesia in laboratory animals. In particular, small rodents such as mice is susceptible to hypothermia during anesthetic events. Therefore, the animals will need additional thermal support by external heating devices during and after anesthesia. In general, the time of recovery from anesthesia is typically longer in case of injectable anesthesia rather than inhalant anesthesia. However, the durations of thermal support have been almost limited to 1 hr from administration of anesthesia in general. Our study objectives are two-fold: 1) to compare the levels of hypothermia induced by injectable anesthesia with medetomidine-midazolam-butorphanol (MMB) and inhalant anesthesia with isoflurane (ISO); 2) to find the adequate durations of thermal support for preventing hypothermia induced by their anesthesia in mice. Adult male ICR mice were anesthetized during 40 min without and with the thermal support for 1 (both anesthetic groups), 2, 3, and 5 hr (in MMB group). Without thermal support, the decrease of body temperature in MMB group were more severe than that in ISO group. The durations of thermal support completely prevented hypothermia at 5 hr-support in MMB group and that at 1 hr-support in ISO group. However, the other short durations did not prevent hypothermia at 1, 2 and 3 hr-support in MMB group. These results suggest that the mice should be received thermal support over 5 hr after injection of MMB anesthesia to prevent hypothermia.


Assuntos
Anestesia , Hipotermia , Anestesia/efeitos adversos , Anestesia/veterinária , Anestésicos Combinados , Animais , Butorfanol , Hipotermia/induzido quimicamente , Hipotermia/prevenção & controle , Hipotermia/veterinária , Masculino , Medetomidina , Camundongos , Camundongos Endogâmicos ICR , Midazolam
11.
J Am Assoc Lab Anim Sci ; 59(6): 719-725, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32907696

RESUMO

Accurate pain assessment methods are necessary to ensure animal welfare and reliable data collection in animal research. The Rat Grimace Scale (RGS), a facial expression pain scale, allows effective identification of pain. However, the potential confounds of this method remain mostly unexplored. General anesthesia, which is used in many laboratory procedures, suppresses thermoregulation and results in hypothermia. We investigated the effects of isoflurane-induced hypothermia on RGS scores. Twenty (10 male and 10 female) Sprague-Dawley rats each received 30 min of anesthesia, followed by 30 min of observation after the return of sternal recumbency. Rats were randomized to receive warming with an electric heating pad or no warming during both periods. Unwarmed rats became hypothermic within 15 min after isoflurane exposure began and returned to normothermia within 15 min after returning to sternal recumbency. Warmed rats did not deviate from the normothermic range. The RGS scores of unwarmed rats were significantly higher than baseline levels for 3 h after anesthesia and were higher than those of warmed rats at 5 and 180 min after anesthesia. Hypothermia resulted in a larger proportion of rats crossing a predetermined analgesic intervention threshold. Our findings show that hypothermia induced by isoflurane anesthesia presents a confound to accurate RGS scoring. These results emphasize the importance of maintaining normothermia to avoid inflated pain scores and to obtain accurate pain assessment.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Hipotermia/veterinária , Isoflurano/administração & dosagem , Medição da Dor/veterinária , Ratos Sprague-Dawley , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , Feminino , Hipotermia/induzido quimicamente , Hipotermia/complicações , Masculino , Ratos
13.
J Therm Biol ; 92: 102658, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32888562

RESUMO

The constancy of the activation energy of metabolism (E) for all living organisms is one of the most impressive, though controversial, statements of the modern metabolic theory of evolution. According to WBE-theory suggested by West, Brown, and Enquist, E should be in the range from -0.6 to -0.7 eV. However, there are many examples of significant deviations of E from the predictions of the theory. Now we have conducted a study of this value using rats in different types of pharmacological hypothermia: 1. Short-term (for several hours) hypothermia induced by anesthetic xylazine; 2. Daily torpor-like state induced by the pharmacological composition developed in our previous study. It has been found that in pharmacological daily hypothermia E = -0.56 ± 0.03 eV, which was close to that in daily heterotherms found in literature, E = -0.57 ± 0.04 eV. In short-term hypothermia E was substantially lower, E = -0.17 ± 0.071 eV. Our analysis revealed that in short-term hypothermia, changes in body temperature may lag behind changes in metabolic rate for a period Δt, affecting E. We propose an approach for estimating Δt and obtaining an adjusted E = -0.68 ± 0.17 eV, which corresponds to theoretical predictions. We assume that a similar consideration of Δt should be done when calculating E of daily heterotherms. We assume that in ectotherms, when the ambient temperature changes rapidly, changes in metabolic rate may lag behind changes in body temperature for a period (-) Δt, that should also be considered in E calculations. The proposed approach may contribute to the further development of the metabolic theory of evolution and may be useful in comparing artificial and natural hypothermia, as well as in studying the energy transformations in ecosystems.


Assuntos
Metabolismo Energético , Hipnóticos e Sedativos , Hipotermia/induzido quimicamente , Torpor , Xilazina , Animais , Temperatura Corporal , Regulação da Temperatura Corporal , Metabolismo Energético/efeitos dos fármacos , Hibernação , Hipnóticos e Sedativos/efeitos adversos , Hipotermia/metabolismo , Masculino , Ratos Wistar , Xilazina/efeitos adversos
14.
Sci Rep ; 10(1): 14180, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843655

RESUMO

Na+/K+-ATPase is a transmembrane ion pump that is essential for the maintenance of ion gradients and regulation of multiple cellular functions. Na+/K+-ATPase has been associated with nuclear factor kappa B (NFκB) signalling, a signal associated with lipopolysaccharides (LPSs)-induced immune response in connection with activated Toll-like receptor 4 (TLR4) signalling. However, the contribution of Na+/K+-ATPase to regulating inflammatory responses remains elusive. We report that mice haploinsufficient for the astrocyte-enriched α2Na+/K+-ATPase isoform (α2+/G301R mice) have a reduced proinflammatory response to LPS, accompanied by a reduced hypothermic reaction compared to wild type litter mates. Following intraperitoneal injection of LPS, gene expressions of Tnf-α, Il-1ß, and Il-6 was reduced in the hypothalamus and hippocampus from α2+/G301R mice compared to α2+/+ littermates. The α2+/G301R mice experienced increased expression of the gene encoding an antioxidant enzyme, NRF2, in hippocampal astrocytes. Our findings indicate that α2Na+/K+-ATPase haploinsufficiency negatively modulates LPS-induced immune responses, highlighting a rational pharmacological target for reducing LPS-induced inflammation.


Assuntos
Hipocampo/patologia , Hipotálamo/patologia , Lipopolissacarídeos/toxicidade , Enxaqueca com Aura/enzimologia , ATPase Trocadora de Sódio-Potássio/fisiologia , Animais , Astrócitos/metabolismo , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Introdução de Genes , Heterozigoto , Hipocampo/metabolismo , Hipotálamo/metabolismo , Hipotermia/induzido quimicamente , Hipotermia/enzimologia , Hipotermia/genética , Interleucina-1beta/biossíntese , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-6/biossíntese , Interleucina-6/sangue , Interleucina-6/genética , Macrófagos/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Enxaqueca com Aura/genética , Mutação de Sentido Incorreto , Fator 2 Relacionado a NF-E2/biossíntese , Fator 2 Relacionado a NF-E2/genética , ATPase Trocadora de Sódio-Potássio/deficiência , ATPase Trocadora de Sódio-Potássio/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
15.
Sci Rep ; 10(1): 14160, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843685

RESUMO

Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is "spurious". Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranolol- or pertussis toxin-pretreated mice. It also caused a rapid and reversible drop in rat blood pressure, which did not overlap with IgE-mediated hypotension. These effects could be countered by a bradykinin-B2 receptor antagonist icatibant, and consistently, penicillin indeed increased rat plasma bradykinin. Moreover, penicillin not only directly activated contact system FXII-dependently, but also promoted bradykinin release in plasma incubated-human umbilical vein endothelial cells. In fact, besides penicillin, other beta-lactams also activated the contact system in vitro. Since the autoactivation of FXII can be affected by multiple-factors, plasma from different healthy individuals showed vastly different amidolytic activity in response to penicillin, suggesting the necessity of determining the potency of penicillin to induce individual plasma FXII activation. These results clarify that penicillin-initiated non-allergic anaphylaxis is attributed to contact system activation, which might bring more effective diagnosis options for predicting penicillin-induced fatal risk and avoiding costly and inappropriate treatment clinically.


Assuntos
Anafilaxia/induzido quimicamente , Coagulação Sanguínea/efeitos dos fármacos , Fator XIIa/metabolismo , Sistema Calicreína-Cinina/efeitos dos fármacos , Penicilina G/toxicidade , Anafilaxia/imunologia , Animais , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Bradicinina/fisiologia , Antagonistas dos Receptores da Bradicinina/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipotermia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Penicilina G/efeitos adversos , Toxina Pertussis/toxicidade , Propranolol/toxicidade , Ratos , Ratos Sprague-Dawley , Receptor B2 da Bradicinina/efeitos dos fármacos , Receptor B2 da Bradicinina/fisiologia , beta-Lactamas/toxicidade
17.
Biochem Pharmacol ; 180: 114158, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32702371

RESUMO

Inhibitors of Type 4 cAMP-phosphodiesterases (PDE4s) exert a number of promising therapeutic benefits, including potent anti-inflammatory, memory- and cognition-enhancing, metabolic, and antineoplastic effects. We report here that treatment with a number of distinct PDE4 inhibitors, including Rolipram, Piclamilast, Roflumilast and RS25344, but not treatment with the PDE3-selective inhibitor Cilostamide, induces a rapid (10-30 min), substantial (-5 °C) and long-lasting (up to 5 h) decrease in core body temperature of C57BL/6 mice; thus, identifying a critical role of PDE4 also in the regulation of body temperature. As little as 0.04 mg/kg of the archetypal PDE4 inhibitor Rolipram induces hypothermia. As similar or higher doses of Rolipram were used in a majority of published animal studies, most of the reported findings are likely paralleled by, or potentially impacted by hypothermia induced by these drugs. We further show that PDE4 inhibition affects central body temperature regulation and acts by lowering the cold-defense balance point of behavioral (including posture and locomotion) and autonomous (including cutaneous tail vasodilation) cold-defense mechanisms. In line with the idea of an effect on central body temperature regulation, hypothermia is induced by moderate doses of various brain-penetrant PDE4 inhibitors, but not by similar doses of YM976, a PDE4 inhibitor that does not efficiently cross the blood-brain barrier. Finally, to begin delineating the mechanism of drug-induced hypothermia, we show that blockade of D2/3-type dopaminergic, but not ß-adrenergic, H1-histaminergic or opiate receptors, can alleviate PDE4 inhibitor-induced hypothermia. We thus propose that increased D2/3-type dopaminergic signaling, triggered by PDE4 inhibitor-induced and cAMP-mediated dopamine release in the thermoregulatory centers of the hypothalamus, is a significant contributor to PDE4 inhibitor-induced hypothermia.


Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Hipotermia/induzido quimicamente , Hipotermia/metabolismo , Locomoção/fisiologia , Inibidores da Fosfodiesterase 4/toxicidade , Animais , Benzamidas/farmacologia , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Regulação da Temperatura Corporal/fisiologia , Relação Dose-Resposta a Droga , Feminino , Hipotermia/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores da Fosfodiesterase 4/farmacologia , Piridinas/farmacologia
18.
Drug Alcohol Depend ; 214: 108166, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717503

RESUMO

The use of Δ9-tetrahydrocannabinol (THC) by inhalation using e-cigarette technology grows increasingly popular for medical and recreational purposes. This has led to development of e-cigarette based techniques to study the delivery of THC by inhalation in laboratory rodents. Inhaled THC reliably produces hypothermic and antinociceptive effects in rats, similar to effects of parenteral injection of THC. This study was conducted to determine the extent to which the hypothermic response depends on interactions with the CB1 receptor, using pharmacological antagonist (SR141716, AM-251) approaches. Groups of rats were implanted with radiotelemetry devices capable of reporting activity and body temperature, which were assessed after THC inhalation or injection. SR141716 (4 mg/kg, i.p.) blocked or attenuated antinociceptive effects of acute THC inhalation in male and female rats. SR141716 was unable to block the initial hypothermia caused by THC inhalation, but temperature was restored to normal more quickly. Alterations in antagonist pre-treatment time, dose and the use of a rat strain with less sensitivity to THC-induced hypothermia did not change this pattern. Pre-treatment with SR141716 (4 mg/kg, i.p.) blocked hypothermia induced by i.v. THC and reversed hypothermia when administered 45 or 90 min after THC (i.p.). SR141716 and AM-251 (4 mg/kg, i.p.) sped recovery from, but did not block, hypothermia caused by vapor THC in female rats made tolerant by prior repeated THC vapor inhalation. The CB2 antagonist AM-630, had no effect. These results suggest that hypothermia consequent to THC inhalation is induced by other mechanisms in addition to CB1 receptor activation.


Assuntos
Dronabinol/farmacologia , Sistemas Eletrônicos de Liberação de Nicotina , Hipotermia/induzido quimicamente , Receptor CB1 de Canabinoide/metabolismo , Administração por Inalação , Animais , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Dronabinol/administração & dosagem , Feminino , Injeções , Masculino , Ratos , Rimonabanto/farmacologia
19.
BMC Psychiatry ; 20(1): 290, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517724

RESUMO

BACKGROUND: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. CASE PRESENTATION: A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89 °F (31.7 °C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. DISCUSSION: While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drug-disease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. CONCLUSIONS: Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.


Assuntos
Antipsicóticos/efeitos adversos , Regulação da Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Clozapina/administração & dosagem , Clozapina/efeitos adversos , Hipotermia/induzido quimicamente , Idoso , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Pacientes Internados
20.
Ann Afr Med ; 19(2): 137-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32499471

RESUMO

Objective: Administration of warm intravenous (IV) fluid infusion and use of forced air warmers is the most easy and physiologically viable method for maintaining normothermia during surgery and postsurgical periods This study was conducted to assess the effect of combination of active warming (AW) methods namely warm IV fluid infusion and forced air warming versus forced air warming only (WA) on maternal temperature during elective C-delivery under spinal anesthesia. Materials and Methods: A total of 100 patients scheduled for elective c-section were grouped into those who received both warmed IV fluid infusion and forced air warmer (Combination of active warming WI= 50) and those who received only forced air warmer (WA = 50). Core body temperature and shivering incidence were recorded using a tympanic thermometer from prespinal till the end of surgery every 10 min and in postanesthesia care unit (PACU) at 0, 15, and 30 min. Results: Core temperature showed statistically significant difference in 15, 35, 45, and 55 min between air warmer and warm infusion groups and in PACU at 0, 15, and 30 min, it was statistically significant (P = 0.000) among WI group (mean temperature = 36.79°C) when compared to WA group (mean temperature = 35.96°C). There was a lower incidence of shivering in WI compared to WA group, which is statistically significant. Conclusion: Combination of warm Intravenous fluid infusion and Forced air warming is better than forced air warming alone. In maintaining near normal maternal core body temperature during elective cesarean section following spinal anesthesia. Combined warming method also reduces shivering incidence.


Assuntos
Anestesia Obstétrica/métodos , Raquianestesia/efeitos adversos , Cesárea/efeitos adversos , Temperatura Alta/uso terapêutico , Hipotermia/prevenção & controle , Infusões Intravenosas/métodos , Cuidados Intraoperatórios/métodos , Administração Intravenosa , Adulto , Período de Recuperação da Anestesia , Anestesia Obstétrica/efeitos adversos , Raquianestesia/métodos , Regulação da Temperatura Corporal , Cesárea/métodos , Feminino , Humanos , Hipotermia/induzido quimicamente , Hipotermia/etiologia , Monitorização Intraoperatória/métodos , Gravidez , Tremor por Sensação de Frio/efeitos dos fármacos , Tremor por Sensação de Frio/fisiologia , Fatores de Tempo , Resultado do Tratamento
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