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1.
Medicine (Baltimore) ; 99(45): e23061, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157963

RESUMO

OBJECTIVE: This study is aims to compare the anesthetic safety of propofol combined with etomidate for painless gastroscopy. METHODS: Three hundred patients undergoing painless gastroscopy were randomly assigned to P, PE1, and PE2 groups. Patients were anesthetized with propofol (P group) or propofol combined with etomidate (volume ratio 1: 1, PE1 group; volume ratio 2: 1, PE2 group). The hemodynamics and adverse reactions were observed. The sleep quality satisfaction and nature of dreams were recorded. RESULTS: Compared with pre-anesthesia, the mean arterial pressure and heart rate of the 3 groups were significantly slower during the examination and at the end of the examination. PE1 group had a higher incidence of muscle spasm, body moving, choking, and deglutition. The incidence of hypoxemia and injection pain was higher in P group. P and PE2 group had higher sleep quality satisfaction and dream incidence after awaking. However, there was no difference in the nature of dreams among 3 groups. CONCLUSION: Our data indicate that the combination of 10 ml 1.0% propofol and 5 ml 0.2% etomidate for painless gastroscopy reduces adverse reactions while not affecting the patients respiratory function. Moreover, it is safe and effective, which is worthy of clinical application and promotion.


Assuntos
Anestésicos Intravenosos/efeitos adversos , Etomidato/efeitos adversos , Gastroscopia/métodos , Propofol/efeitos adversos , Adulto , Obstrução das Vias Respiratórias/induzido quimicamente , Anestésicos Intravenosos/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Estudos de Casos e Controles , Quimioterapia Combinada , Etomidato/administração & dosagem , Feminino , Gastroscopia/tendências , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipóxia/induzido quimicamente , Incidência , Reação no Local da Injeção , Masculino , Pessoa de Meia-Idade , Mioclonia/induzido quimicamente , Propofol/administração & dosagem , Segurança , Espasmo/induzido quimicamente , Espasmo/epidemiologia , Resultado do Tratamento
2.
Infect Dis (Lond) ; 52(9): 659-661, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496938

RESUMO

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemólise , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Idoso , Azitromicina/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Transfusão de Sangue , Terapia de Substituição Renal Contínua , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Haptoglobinas/análise , Humanos , Hidroxicloroquina/uso terapêutico , Hipóxia/induzido quimicamente , Hipóxia/complicações , Masculino , Nasofaringe/virologia , Pandemias , Vírus da SARS/genética , Vírus da SARS/isolamento & purificação
3.
Artigo em Russo | MEDLINE | ID: mdl-32323948

RESUMO

A case of acute oral poisoning by 1.4-butanediol, complicated by the development of severe hypoxia in a 34-year-old patient actively engaged in bodybuilding, is presented. The psychoactive substance was used by the patient to increase sexual activity and physical stamina. The duration of systematic daily intake was 4 months. The toxicogenic stage of acute poisoning was caused by a single dose of 50 ml of undiluted 13% 1.4-butanediol together with ethanol, manifested by convulsive syndrome, depression of consciousness to the level of coma II, acute respiratory failure with aspiration syndrome, respiratory acidosis (pH 7.22; partial pressure carbon dioxide 61.2 mm Hg), lactic acidosis up to 7 mmol / L, hyperammonemia up to 240 µmol / L, cerebral edema (decrease in white matter density to 21.6 ± 1.7 HU units), loss of vascular tone resistance (pareso arterioles) and a significant increase in cerebral blood flow rate to 115 ± 20.1 ml / 100 g per minute, increasing the volume of extracellular fluid (+ 130% of the proper volumes). Intensive therapy was complex, including infusion and detoxification therapy, correction of acid-base disorders, hypoxic disorders by using a substrate antihypoxant (Cytoflavin) in a daily dosage of 0.57 ml / kg body weight daily, for 9 days. The article discusses the toxicokinetics and toxicodynamics of 1.4-butanediol, radiation diagnostics and the clinical picture of acute poisoning, the features of its course, and pathogenetic approaches to therapy.


Assuntos
Butileno Glicóis/administração & dosagem , Butileno Glicóis/envenenamento , Coma/induzido quimicamente , Etanol/administração & dosagem , Etanol/envenenamento , Adulto , Coma/complicações , Humanos , Hipóxia/induzido quimicamente , Hipóxia/complicações
4.
Acta Orthop ; 91(3): 293-298, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32237931

RESUMO

Background and purpose - The bone cement implantation syndrome characterized by hypotension and/or hypoxia is a well-known complication in cemented arthroplasty. We studied the incidence of hypotension and/or hypoxia in patients undergoing cemented or uncemented hemiarthroplasty for femoral neck fractures and evaluated whether bone cement was an independent risk factor for postoperative mortality.Patients and methods - In this retrospective cohort study, 1,095 patients from 2 hospitals undergoing hemiarthroplasty with (n = 986) and without (n = 109) bone cementation were included. Pre-, intra-, and postoperative data were obtained from electronic medical records. Each patient was classified for grade of hypotension and hypoxia during and after prosthesis insertion according to Donaldson's criteria (Grade 1, 2, 3). After adjustments for confounders, the hazard ratio (HR) for the use of bone cement on 1-year mortality was assessed.Results - The incidence of hypoxia and/or hypotension was higher in the cemented (28%) compared with the uncemented group (17%) (p = 0.003). The incidence of severe hypotension/hypoxia (grade 2 or 3) was 6.9% in the cemented, but not observed in the uncemented group. The use of bone cement was an independent risk factor for 1-year mortality (HR 1.9, 95% CI 1.3-2.7), when adjusted for confounders.Interpretation - The use of bone cement in hemiarthroplasty for femoral neck fractures increases the incidence of intraoperative hypoxia and/or hypotension and is an independent risk factor for postoperative 1-year mortality. Efforts should be made to identify patients at risk for BCIS and alternative strategies for the management of these patients should be considered.


Assuntos
Artroplastia de Quadril/efeitos adversos , Cimentos para Ossos/efeitos adversos , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Hipotensão/induzido quimicamente , Hipóxia/induzido quimicamente , Complicações Intraoperatórias/induzido quimicamente , Idoso de 80 Anos ou mais , Artroplastia de Quadril/métodos , Artroplastia de Quadril/mortalidade , Cimentos para Ossos/uso terapêutico , Feminino , Fraturas do Colo Femoral/mortalidade , Hemiartroplastia/métodos , Hemiartroplastia/mortalidade , Humanos , Masculino , Estudos Retrospectivos
5.
Ann N Y Acad Sci ; 1479(1): 168-179, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32242940

RESUMO

Exposure to phosphine (PH3 ), a common grain fumigant, is characterized by diverse nonspecific symptoms and a high mortality rate. Although PH3 poisoning is thought to target oxidative respiration, the exact mechanism of action remains largely unknown, resulting in limited treatment options. In our study, the effects of PH3 on female rats were assessed to elucidate potential sex-specific differences and obtain a more comprehensive understanding of PH3 toxicity. Lethality, physiology, and behavior were evaluated in female rats exposed to gaseous PH3 (13,200-26,400 ppm × min), and results were compared with corresponding findings in male rats. Median lethal concentration-time (LCt50 ) and time of death (tTOD ) did not differ significantly between the sexes. Cardiopulmonary changes induced by PH3 were also of comparable magnitude, although temporally, respiratory responses occurred earlier and cardiovascular variations manifested later in female rats. Behavioral observations corroborated physiological findings and indicated a response to hypoxic conditions and low cardiac output. Together, these results provided insights on the toxic mechanisms of PH3 , in particular, its potential interference with oxygen transport and circulation.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Baixo Débito Cardíaco , Hipóxia , Oxigênio/sangue , Fosfinas/envenenamento , Caracteres Sexuais , Animais , Baixo Débito Cardíaco/sangue , Baixo Débito Cardíaco/induzido quimicamente , Baixo Débito Cardíaco/fisiopatologia , Feminino , Hipóxia/sangue , Hipóxia/induzido quimicamente , Hipóxia/fisiopatologia , Ratos , Ratos Sprague-Dawley
6.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165753, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32126269

RESUMO

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated to intermittent hypoxia (IH) and is an aggravating factor of non-alcoholic fatty liver disease (NAFLD). We investigated the effects of hypoxia in both in vitro and in vivo models of NAFLD. METHODS: Primary rat hepatocytes treated with free fatty acids (FFA) were subjected to chemically induced hypoxia (CH) using the hypoxia-inducible factor-1 alpha (HIF-1α) stabilizer cobalt chloride (CoCl2). Triglyceride (TG) content, mitochondrial superoxide production, cell death rates, cytokine and inflammasome components gene expression and protein levels of cleaved caspase-1 were assessed. Also, Kupffer cells (KC) were treated with conditioned medium (CM) and extracellular vehicles (EVs) from hypoxic fat-laden hepatic cells. The choline deficient L-amino acid defined (CDAA)-feeding model used to assess the effects of IH on experimental NAFLD in vivo. RESULTS: Hypoxia induced HIF-1α in cells and animals. Hepatocytes exposed to FFA and CoCl2 exhibited increased TG content and higher cell death rates as well as increased mitochondrial superoxide production and mRNA levels of pro-inflammatory cytokines and of inflammasome-components interleukin-1ß, NLRP3 and ASC. Protein levels of cleaved caspase-1 increased in CH-exposed hepatocytes. CM and EVs from hypoxic fat-laden hepatic cells evoked a pro-inflammatory phenotype in KC. Livers from CDAA-fed mice exposed to IH exhibited increased mRNA levels of pro-inflammatory and inflammasome genes and increased levels of cleaved caspase-1. CONCLUSION: Hypoxia promotes inflammatory signals including inflammasome/caspase-1 activation in fat-laden hepatocytes and contributes to cellular crosstalk with KC by release of EVs. These mechanisms may underlie the aggravating effect of OSAS on NAFLD. [Abstract word count: 257].


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Hepatopatia Gordurosa não Alcoólica/genética , Apneia Obstrutiva do Sono/genética , Animais , Caspase 1/genética , Deficiência de Colina/genética , Deficiência de Colina/metabolismo , Deficiência de Colina/patologia , Cobalto/toxicidade , Modelos Animais de Doenças , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Ácidos Graxos não Esterificados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Hipóxia/induzido quimicamente , Hipóxia/metabolismo , Hipóxia/patologia , Inflamassomos/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/genética , Macrófagos do Fígado/metabolismo , Macrófagos do Fígado/patologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Triglicerídeos/genética
7.
Anesthesiology ; 132(5): 1138-1150, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32044798

RESUMO

BACKGROUND: As severe acute hypoxemia produces a rapid inhibition of the respiratory neuronal activity through a nonopioid mechanism, we have investigated in adult rats the effects of hypoxemia after fentanyl overdose-induced apnea on (1) autoresuscitation and (2) the antidotal effects of naloxone. METHODS: In nonsedated rats, the breath-by-breath ventilatory and pulmonary gas exchange response to fentanyl overdose (300 µg · kg · min iv in 1 min) was determined in an open flow plethysmograph. The effects of inhaling air (nine rats) or a hypoxic mixture (fractional inspired oxygen tension between 7.3 and 11.3%, eight rats) on the ability to recover a spontaneous breathing rhythm and on the effects of naloxone (2 mg · kg) were investigated. In addition, arterial blood gases, arterial blood pressure, ventilation, and pulmonary gas exchange were determined in spontaneously breathing tracheostomized urethane-anesthetized rats in response to (1) fentanyl-induced hypoventilation (7 rats), (2) fentanyl-induced apnea (10 rats) in air and hyperoxia, and (3) isolated anoxic exposure (4 rats). Data are expressed as median and range. RESULTS: In air-breathing nonsedated rats, fentanyl produced an apnea within 14 s (12 to 29 s). A spontaneous rhythmic activity always resumed after 85.4 s (33 to 141 s) consisting of a persistent low tidal volume and slow frequency rhythmic activity that rescued all animals. Naloxone, 10 min later, immediately restored the baseline level of ventilation. At fractional inspired oxygen tension less than 10%, fentanyl-induced apnea was irreversible despite a transient gasping pattern; the administration of naloxone had no effects. In sedated rats, when PaO2 reached 16 mmHg during fentanyl-induced apnea, no spontaneous recovery of breathing occurred and naloxone had no rescuing effect, despite circulation being maintained. CONCLUSIONS: Hypoxia-induced ventilatory depression during fentanyl induced apnea (1) opposes the spontaneous emergence of a respiratory rhythm, which would have rescued the animals otherwise, and (2) prevents the effects of high dose naloxone.


Assuntos
Analgésicos Opioides/toxicidade , Fentanila/toxicidade , Hipóxia/fisiopatologia , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Vigília/efeitos dos fármacos , Animais , Hipnóticos e Sedativos/toxicidade , Hipóxia/induzido quimicamente , Hipóxia/tratamento farmacológico , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Índice de Gravidade de Doença , Vigília/fisiologia
8.
Nutrients ; 12(2)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092924

RESUMO

Acai (Euterpe oleracea Mart. Palmae, Arecaceae) is a palm plant native to the Brazilian Amazon. It contains many nutrients, such as polyphenols, iron, vitamin E, and unsaturated fatty acids, so in recent years, many of the antioxidant and anti-inflammatory effects of acai have been reported. However, the effects of acai on hematopoiesis have not been investigated yet. In the present study, we administered acai extract to mice and evaluated its hematopoietic effects. Acai treatment significantly increased the erythrocytes, hemoglobin, and hematocrit contents compared to controls for four days. Then, we examined the hematopoietic-related markers following a single injection. Acai administration significantly increased the levels of the hematopoietic-related hormone erythropoietin in blood compared to controls and also transiently upregulated the gene expression of Epo in the kidney. Furthermore, in the mice treated with acai extract, the kidneys were positively stained with the hypoxic probe pimonidazole in comparison to the controls. These results demonstrated that acai increases the erythropoietin expression via hypoxic action in the kidney. Acai can be expected to improve motility through hematopoiesis.


Assuntos
Eritropoetina/metabolismo , Euterpe/química , Hematínicos/farmacologia , Hipóxia/induzido quimicamente , Extratos Vegetais/farmacologia , Animais , Brasil , Modelos Animais de Doenças , Hematopoese/efeitos dos fármacos , Rim/efeitos dos fármacos , Camundongos , Regulação para Cima/efeitos dos fármacos
9.
Anaesthesia ; 75(3): 338-347, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31420989

RESUMO

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected.


Assuntos
Hipóxia/induzido quimicamente , Hipóxia/fisiopatologia , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Ventilação Pulmonar , Rocurônio/efeitos adversos , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Adulto , Idoso , Dióxido de Carbono/sangue , Humanos , Hipercapnia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Prospectivos , Músculos Respiratórios/efeitos dos fármacos , Músculos Respiratórios/fisiopatologia , Fatores de Risco , Adulto Jovem
10.
Biol Pharm Bull ; 43(3): 432-439, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875579

RESUMO

Salvia przewalskii Maxim is a traditional Chinese herbal medicine and is known to have antibacterial, antiviral, anti-oxidant, anti-thrombotic and anti-depressant properties. However, the major active components of S. przewalskii and its anti-hypoxic effects are still unclear. This study probed the major active component and anti-hypoxic activity of S. przewalskii. The major active components of S. przewalskii were detected by HPLC. The anti-hypoxic effects of S. przewalskii were detected in mice and a rat model of hypoxic preconditioning. The results showed that there are eight active components, including sodium danshensu, rosmarinic acid, lithospermic acid, salvianolic acid B, dihydrotanshinone I, cryptotanshinone, tanshinone I and tanshinone IIA, and each component showed a certain anti-hypoxic effect. Moreover, S. przewalskii enhanced anti-hypoxia in mice, which was manifested as prolonged survival time in acute hypoxic preconditioning and the amelioration of acute hypoxia-induced changes in the activity of superoxide dismutase (SOD) and lactate dehydrogenase (LDH). In addition, S. przewalskii also repaired tissue damage in chronic hypoxia by downregulating hypoxia inducible factor-1α (HIF-1α), proliferating cell nuclear antigen (PCNA), Bcl-2, CDK4, CyclinD1 and P27Kip1 and inhibiting pro-inflammatory cytokines and the RhoA-Rho-associated protein kinase (ROCK) signalling pathway. Our findings provide new insight into the anti-hypoxic effect of S. przewalskii as a promising agent for high-altitude pulmonary hypertension treatment.


Assuntos
Hipóxia/tratamento farmacológico , Extratos Vegetais/farmacologia , Salvia/química , Quinases Associadas a rho/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Coração/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/induzido quimicamente , Camundongos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
11.
A A Pract ; 14(2): 60-62, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31770132

RESUMO

Clevidipine-induced pulmonary shunting is a little-reported adverse effect, manifesting as refractory hypoxemia, which may cause significant patient harm. We present the case of a mechanically ventilated patient admitted to the intensive care unit following a neurosurgical procedure. He was treated postoperatively with clevidipine for blood pressure management, and within 16 hours, he developed profound refractory hypoxemia, requiring increased ventilatory support. A workup for other causes was negative. The hypoxemia recovered within 1 hour of clevidipine discontinuation. Though other calcium channel blockers have been reported to cause pulmonary shunting from vasodilation, this is a novel case report for clevidipine-induced hypoxemia.


Assuntos
Hipóxia/induzido quimicamente , Procedimentos Neurocirúrgicos/efeitos adversos , Piridinas/efeitos adversos , Adolescente , Humanos , Hipertensão/tratamento farmacológico , Masculino , Respiração Artificial
12.
Life Sci ; 238: 116876, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655194

RESUMO

AIMS: Adiponectin (APN) is a protein hormone secreted mainly by adipose tissue that exhibits biological functions such as anti-inflammatory, anti-atherosclerotic, anti-apoptotic, hearing-protective and microcirculation-regulating functions. In this study, we explored whether APN could attenuate damage caused by CoCl2-induced hypoxic conditions in smooth muscle cells (SMCs) of the spiral modiolar artery (SMA). MAIN METHODS: We first cultured and identified primary SMCs of the SMA. Afterward, the SMCs were pre-treated with APN and then stimulated with CoCl2. KEY FINDINGS: Compared with the control group, the group treated with CoCl2 for 24 h exhibited significantly decreased cell viability, significantly increased apoptosis rates and Malondialdehyde (MDA) levels, and decreased Superoxide Dismutase (SOD) activity. In addition, the expression levels of Bax and cleaved caspase-3 were upregulated, while those of Bcl2 were downregulated evidently. Compared with the CoCl2 group, the group pre-treated with APN before receiving CoCl2 treatment had increased cell viability and SOD activity but decreased MDA levels and apoptosis rates. The expression levels of Bcl2, p-AMPKα and Cx43 were evidently increased, while those of Bax and cleaved caspase-3 were decreased, in the group pre-treated with APN compared to the CoCl2 group. The protective effect of APN was blocked by the AMPK inhibitor Compound C and the Cx43 inhibitor Gap19. SIGNIFICANCE: Our study demonstrated that APN protected SMCs against CoCl2-induced hypoxic injury via the AMPK signalling pathway and regulated the expression of Cx43 in cells. Therefore, APN might be a promising treatment for diseases related to circulation disturbances of the inner ear.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/farmacologia , Apoptose/efeitos dos fármacos , Artérias/efeitos dos fármacos , Cóclea/irrigação sanguínea , Conexina 43/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Animais , Antimutagênicos/toxicidade , Artérias/metabolismo , Artérias/patologia , Cobalto/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Cobaias , Hipóxia/induzido quimicamente , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Hipóxia/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Espécies Reativas de Oxigênio
13.
Mar Drugs ; 17(11)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31652920

RESUMO

The hypoxia/reoxygenation (H/R) injury causes serious complications after the blood supply to the kidney is stopped during surgery. The main mechanism of I/R injury is the release of high-mobility group protein B1 (HMGB1) from injured tubular epithelial cells (TEC, TCMK-1 cell), which triggers TLR4 or RAGE signaling, leading to cell death. We evaluated whether the extracts of Ecklonia cava (E. cava) would attenuate TEC death induced by H/R injury. We also evaluated which phlorotannin-dieckol (DK), phlorofucofuroeckol A (PFFA), pyrogallol phloroglucinol-6,6-bieckol (PPB), or 2,7-phloroglucinol-6,6-bieckol (PHB)-would have the most potent effect in the context of H/R injury. We used for pre-hypoxia treatment, in which the phlorotannins from E. cava extracts were added before the onset of hypoxia, and a post- hypoxia treatment, in which the phlorotannins were added before the start of reperfusion. PPB most effectively reduced HMGB1 release and the expression of TLR4 and RAGE induced by H/R injury in both pre- and post-hypoxia treatment. PPB also most effectively inhibited the expression of NF-kB and release of the inflammatory cytokines TNF-α and IL-6 in both models. PPB most effectively inhibited cell death and expression of cell death signaling molecules such as Erk/pErk, JNK/pJNK, and p38/pp38. These results suggest that PPB blocks the HGMB1-TLR4/RAGE signaling pathway and decreases TEC death induced by H/R and that PPB can be a novel target for renal H/R injury therapy.


Assuntos
Hipóxia/tratamento farmacológico , Feófitas/química , Pirogalol/farmacologia , Animais , Linhagem Celular , Citocinas/metabolismo , Dioxinas/farmacologia , Células Epiteliais/efeitos dos fármacos , Proteína HMGB1/metabolismo , Hipóxia/induzido quimicamente , Rim/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Taninos/farmacologia , Receptor 4 Toll-Like/metabolismo
14.
Gastrointest Endosc ; 90(4): 591-601, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31278907

RESUMO

BACKGROUND AND AIMS: Hypoxia is one of the most frequent adverse events with sedated GI endoscopy and can lead to serious consequences. No modalities have been found previously to prevent hypoxia. High-flow nasal cannula (HFNC) supportive oxygen therapy provides heated and humidified oxygen up to 60 L/minute. Because of its ability to improve respiratory function and good tolerance, we aimed to evaluate the validity and safety of HFNC supportive oxygen therapy in preventing the incidence of hypoxia in patients undergoing gastroscopy with propofol sedation. METHODS: In a multicenter, prospective randomized single-blinded study, 1994 outpatients undergoing routine gastroscopy with propofol sedation provided by an anesthesiologist were randomized into 2 groups: the nasal cannula group (O2 [2 L/minute] was supplied via an HFNC) and the HFNC group (O2 [30-60 L/minute] was supplied via an HFNC) at 3 centers from November 2017 to February 2018. The primary outcome was the incidence of hypoxia. Other adverse events were also recorded. RESULTS: HFNC supportive oxygen therapy decreased the incidence of hypoxia (75% ≤ Spo2 < 90% for <60 seconds) and severe hypoxia (Spo2 < 75% for any duration or 75% ≤ Spo2 < 90% for ≥60 seconds) from 8.4% to 0% (P < .001) and from 0.6% to 0% (P = .03), respectively. The only HFNC-related adverse event was xeromycteria/rhinalgia (1.7%), which was observed 1 minute after the procedure and disappeared after 30 minutes. CONCLUSIONS: HFNC supportive oxygen therapy can prevent the incidence of hypoxia and severe hypoxia in patients in America Society of Anesthesiologists class I-II undergoing elective gastroscopy under propofol sedation, with minimal related adverse events and good tolerance. (Clinical trial registration number: NCT03332433.).


Assuntos
Gastroscopia/métodos , Hipóxia/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Oxigenoterapia/métodos , Adulto , Idoso , Cânula , Delírio do Despertar/epidemiologia , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipóxia/induzido quimicamente , Hipóxia/epidemiologia , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Propofol/efeitos adversos , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/epidemiologia , Índice de Gravidade de Doença
15.
Vet Anaesth Analg ; 46(4): 466-475, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31176572

RESUMO

OBJECTIVE: To compare immobilization efficacy of a nonpotent opioid drug combination, ketamine-butorphanol-medetomidine (KBM) to the preferred etorphine-azaperone (EA) combination in zebras. STUDY DESIGN: Randomized crossover trial. ANIMALS: A group of ten adult zebra (six females and four male). METHODS: KBM and EA were administered once to the zebras in random order by dart, 3 weeks apart. Once a zebra was recumbent and instrumented, physiological parameters were measured and recorded at 5-minute intervals until 20 minutes. Antagonist drugs were administered at 25 minutes. KBM was antagonised using atipamezole (7.5 mg mg-1 medetomidine dose) and naltrexone (2 mg mg-1 butorphanol dose). EA was antagonized using naltrexone (20 mg mg-1 etorphine dose). Induction and recovery (following antagonist administration) times were recorded. Physiological parameters, including invasive blood pressure and blood gas analysis, were compared between combinations using a general linear mixed model. Data are reported as mean ± standard deviation or median (interquartile range). RESULTS: The doses of KBM and EA administered were 3.30 ± 0.18, 0.40 ± 0.02 and 0.16 ± 0.01 mg kg-1; and 0.02 ± 0.001 and 0.20 ± 0.01 mg kg-1, respectively. KBM and EA induction times were 420 (282-564) and 240 (204-294) seconds, respectively (p = 0.03). Zebras remained recumbent throughout the study procedures. Systolic blood pressure (226 ± 42 and 167 ± 42 mmHg) and oxygen partial pressure (64 ± 12 and 47 ± 13 mmHg) were higher for KBM compared to EA (p < 0.01). Recovery time, after administering antagonists, was 92 (34-1337) and 26 (22-32) seconds for KBM and EA, respectively (p = 0.03). CONCLUSIONS AND CLINICAL RELEVANCE: Compared to EA, KBM also immobilized zebras effectively. Systemic hypertension and moderate hypoxaemia are clinical concerns of KBM and severe hypoxaemia is a concern of EA. This occurrence of hypoxaemia highlights the importance of oxygen administration during immobilization.


Assuntos
Analgésicos Opioides/farmacologia , Anestésicos Dissociativos/farmacologia , Equidae , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Dissociativos/administração & dosagem , Animais , Animais Selvagens , Azaperona/administração & dosagem , Azaperona/efeitos adversos , Azaperona/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Butorfanol/administração & dosagem , Butorfanol/farmacologia , Estudos Cross-Over , Combinação de Medicamentos , Etorfina/administração & dosagem , Etorfina/efeitos adversos , Etorfina/farmacologia , Feminino , Hipertensão/induzido quimicamente , Hipertensão/veterinária , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipóxia/induzido quimicamente , Hipóxia/veterinária , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/farmacologia , Masculino , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Medetomidina/farmacologia , Oxigênio/administração & dosagem , Distribuição Aleatória
16.
Neurourol Urodyn ; 38(6): 1560-1570, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31194269

RESUMO

AIMS: To measure the effects of nicotine on lower urinary tract symptoms (LUTS), bladder blood flow, and the urothelial markers hypoxia-inducible factor 1α (HIF1α), uroplakin III (UPIII), and aquaporin 3 (AQP3). METHODS: Ten-week-old female Sprague Dawley rats were subcutaneously injected with 2 mg/kg nicotine (n = 17) or vehicle (control, n = 18) twice daily for 13 days. Some nicotine-treated rats (n = 10) were injected daily with 1 mg/kg tadalafil for the last 6 days of nicotine treatment. One day before cystometry, the bladders of some nicotine-treated and control rats were instilled with 0.08% acetic acid. Urinary frequency and volume were measured 1 day after treatment. Blood flow in the bladder neck was measured, and the urothelia were immunochemically assayed for HIF1α, UPIII, and AQP3. RESULTS: Following acetic acid treatment, both voiding interval and micturition volume of the nicotine-treated rats were significantly lower than controls. Nicotine-treated rats had lower blood flow than controls, and the urothelial expression of HIF1α was higher than controls. Simultaneously, the expressions of UPIII and AQP3 were decreased. Tadalafil treatment increased bladder blood flow, and nicotine-treated rats had increased voiding interval and micturition volume. Further, the expression of HIF1α decreased, and both UPIII and AQP3 levels increased. CONCLUSIONS: Nicotine-treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. Changes in tissue markers in the nicotine-treated rats were consistent with hypoxia and loss of urothelial function. Restoration of blood flow reversed the nicotine effects. Nicotine may induce LUTS through reduced bladder blood flow and urothelial hypoxia.


Assuntos
Hipóxia/fisiopatologia , Bexiga Urinária/fisiopatologia , Micção/fisiologia , Urotélio/fisiopatologia , Animais , Aquaporina 3/metabolismo , Feminino , Hipóxia/induzido quimicamente , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Nicotina , Ratos , Ratos Sprague-Dawley , Tadalafila/farmacologia , Bexiga Urinária/metabolismo , Uroplaquina III/metabolismo , Urotélio/metabolismo
17.
Medicine (Baltimore) ; 98(20): e15712, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096522

RESUMO

BACKGROUND: Sedation with etomidate or propofol alone during gastroscopy has many side effects. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of the combined use of propofol and etomidate for sedation during gastroscopy. METHODS: PubMed, Embase, Medline (via Ovid SP), Cochrane library databases, CINAHL (via EBSCO), China Biology Medicine disc (CBMdisc), Wanfang, VIP, and China National Knowledge Infrastructure (CNKI) databases were systematically searched. We included randomized controlled trials (RCTs) comparing the combined use of propofol and etomidate vs etomidate or propofol alone for sedation during gastroscopy. Data were pooled using the random-effects models or fixed-effect model based on heterogeneity. RESULTS: Fifteen studies with 2973 participants were included in the analysis. Compared to propofol alone, the combined use of propofol and etomidate possibly increased recovery time (SMD = 0.14, 95% CI = 0.04-0.24; P = .005), and the risk for myoclonus (OR = 3.07, 95% CI = 1.73-5.44; P < .001), injection pain, and nausea and vomiting. Furthermore, compared to propofol alone, the combination of propofol and etomidate produced an apparent beneficial effect for mean arterial pressure (MAP) after anesthesia (SMD = 1.32, 95% CI = 0.38-2.26; P = .006), SPO2 after anesthesia (SMD = 0.99, 95% CI = 0.43-1.55; P < .001), apnea or hypoxemia (OR = 0.16, 95% CI = 0.08-0.33; P < .001), injection pain, and body movement. Further, compared to etomidate alone, the combination of propofol and etomidate reduced the risk for myoclonus (OR = 0.15, 95% CI = 0.11-0.22; P < .001), body movement, and nausea and vomiting. CONCLUSION: The combination of propofol and etomidate might increase recovery time vs that associated with propofol, but it had fewer side effects on circulation and respiration in patients undergoing gastroscopy. The combined use of propofol and etomidate can improve and produce an apparent beneficial effect on the adverse effects of propofol or etomidate alone, and it was safer and more effective than propofol or etomidate alone.


Assuntos
Anestésicos Combinados/efeitos adversos , Etomidato/efeitos adversos , Gastroscopia/métodos , Propofol/efeitos adversos , Anestésicos Combinados/administração & dosagem , Anestésicos Combinados/uso terapêutico , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , China/epidemiologia , Etomidato/administração & dosagem , Etomidato/uso terapêutico , Feminino , Humanos , Hipóxia/induzido quimicamente , Reação no Local da Injeção/patologia , Masculino , Mioclonia/induzido quimicamente , Náusea/induzido quimicamente , Propofol/administração & dosagem , Propofol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Vômito/induzido quimicamente
18.
Anesthesiology ; 130(6): 1064-1077, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30998510

RESUMO

Respiratory function is fundamental in the practice of anesthesia. Knowledge of basic physiologic principles of respiration assists in the proper implementation of daily actions of induction and maintenance of general anesthesia, delivery of mechanical ventilation, discontinuation of mechanical and pharmacologic support, and return to the preoperative state. The current work provides a review of classic physiology and emphasizes features important to the anesthesiologist. The material is divided in two main sections, gas exchange and respiratory mechanics; each section presents the physiology as the basis of abnormal states. We review the path of oxygen from air to the artery and of carbon dioxide the opposite way, and we have the causes of hypoxemia and of hypercarbia based on these very footpaths. We present the actions of pressure, flow, and volume as the normal determinants of ventilation, and we review the resulting abnormalities in terms of changes of resistance and compliance.


Assuntos
Anestesia Geral/normas , Anestesiologistas/educação , Anestesiologistas/normas , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia , Anestesia Geral/efeitos adversos , Dióxido de Carbono/metabolismo , Humanos , Hipercapnia/induzido quimicamente , Hipercapnia/fisiopatologia , Hipóxia/induzido quimicamente , Hipóxia/fisiopatologia , Troca Gasosa Pulmonar/efeitos dos fármacos , Troca Gasosa Pulmonar/fisiologia , Respiração Artificial/métodos , Volume de Ventilação Pulmonar/efeitos dos fármacos , Volume de Ventilação Pulmonar/fisiologia
19.
Nat Microbiol ; 4(7): 1196-1207, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30936483

RESUMO

Numerous human APOBEC3 cytidine deaminases have proven to be, inter alia, host cell restriction factors for retroviruses and hepadnaviruses. Although they can bind to genomic RNA and become encapsidated, they are only catalytically active on single-stranded DNA. As there are many cellular deoxyribonucleases (DNases), we hypothesized that a parallel could be struck between APOBEC3 and DNases. For human hepatitis B virus (HBV), we show that DNase I can considerably reduce the virion genome copy number from a variety of transfected or infected cells. DNASE1 is overexpressed and encapsidated in HBV particles in vitro in hypoxic environments and in vivo in cirrhotic patient livers as well as in the serum of infected patients. The use of CoCl2 and dimethyloxalylglycine, mimetic agents used to induce hypoxia by inhibiting prolyl hydroxylase enzymes that stabilize hypoxia-inducible factor (HIF)-1α, showed that the formation of HIF-1α/HIF-1ß heterodimers results in the induction of DNASE1. Indeed, transfection with HIF-1α and HIF-1ß expression constructs upregulated DNASE1. These findings suggest that human DNase I can impact HBV replication through the catabolism of the DNA genome within the capsid. The activity of DNases in general may explain in part the high frequency of empty or 'light' hepatitis B virions observed in vivo.


Assuntos
Desoxirribonuclease I/metabolismo , Vírus da Hepatite B/fisiologia , Hipóxia , Replicação Viral , Linhagem Celular , Cobalto/farmacologia , DNA Viral/metabolismo , Desoxirribonuclease I/genética , Expressão Gênica , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatite B/enzimologia , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Humanos , Hipóxia/induzido quimicamente , Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/enzimologia , Mutação , Vírion/metabolismo , Replicação Viral/efeitos dos fármacos
20.
Respir Res ; 20(1): 79, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023308

RESUMO

BACKGROUND: C-X-C chemokine receptor type 4 (CXCR4) may be involved in the development of pulmonary arterial hypertension (PAH). CXCR4 inhibitor AMD3100 was described to have a positive effect on the prevention of pulmonary arterial muscularization in PAH models. Silibinin is a traditional medicine that has an antagonistic effect on CXCR4. We investigated the effect of silibinin using rat models of PAH. METHODS: PAH was induced by a single subcutaneous injection of monocrotaline. The rats were maintained in a chronic hypoxic condition (10% O2) with or without silibinin. To evaluate the efficacy of silibinin on PAH, right ventricular systolic pressure (RVSP), Fulton index (weight ratio of right ventricle to the left ventricle and septum), percent medial wall thickness (% MT), and vascular occlusion score (VOS) were measured and calculated. Immunohistochemical analysis was performed targeting CXCR4 and c-Kit. Reverse transcription-quantitative polymerase chain reaction was performed for the stem cell markers CXCR4, stromal cell derived factor-1 (SDF-1), c-Kit, and stem cell factor (SCF), and the inflammatory markers monocyte chemoattractant protein 1 (MCP1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). Statistical analyses were performed using t-test and one-way analysis of variance with Bonferroni's post hoc test. RESULTS: Silibinin treatment for 1 week reduced RVSP and Fulton index. Treatment for 2 weeks reduced RVSP, Fulton index, % MT, and VOS, as well as downregulating the expression of CXCR4, SDF-1, and TNFα in pulmonary arteries. In contrast, treatment for 3 weeks failed to ameliorate PAH. The time-course study demonstrated that RVSP, Fulton index, % MT, and VOS gradually increased over time, with a decrease in the expression of CXCR4 and TNFα occurring after 2 weeks of PAH development. After 3 weeks, SDF-1, c-Kit, and SCF began to decrease and, after 5 weeks, MCP1 and IL-6 gradually accumulated. CONCLUSIONS: The CXCR4 inhibitor silibinin can ameliorate PAH, possibly through the suppression of the CXCR4/SDF-1 axis, until the point where PAH becomes a severe and irreversible condition. Silibinin results in reduced pulmonary arterial pressure and delays pulmonary arteriolar occlusion and pulmonary vascular remodeling.


Assuntos
Modelos Animais de Doenças , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Monocrotalina/toxicidade , Receptores CXCR4/antagonistas & inibidores , Silibina/uso terapêutico , Animais , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipóxia/induzido quimicamente , Hipóxia/metabolismo , Masculino , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores CXCR4/fisiologia , Resultado do Tratamento
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