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1.
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
2.
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
3.
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
4.
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
5.
Curr Med Sci ; 39(2): 325-329, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016529

RESUMO

Despite growing attention to patients' safety worldwide, no data were available on the impact of adverse respiratory events (AREs) on post-anesthesia care and post-operation care in China. This study evaluated the occurrence of AREs, the impact of AREs on length of stay (LOS) in post-anesthesia care unit (PACU) and postoperative time in hospital, and PACU cost and inpatient healthcare costs. A retrospective, matched-cohort study was conducted by prospectively collecting the data of 159 AREs in PACU during 2016-2017 in an university hospital in China. Records were reviewed by pre-trained, qualified nurses and/or anesthesiologists. The incidence and the impact of AREs were analyzed. The LOS in PACU and postoperative time in hospital and the costs in PACU and inpatient healthcare costs were also obtained. Results showed that there were 253 AREs involving 156 patients. Hypoxia (n=141, 55.73%) and respiratory depression (n=70, 27.67%) were the most common AREs. Measurement data including body mass index (BMI) (22.85±4.36 vs. 22.32±3.83), duration of procedure (138.47±77.33 min vs. 137.44±72.33 min), duration of anesthesia (176.35±82.66 min vs. 174.61±78.08 min), LOS (16.53±10.65 days vs. 16.57±9.56 days), inpatient healthcare costs ($9465.57±9416.33 vs. $8166.51±5762.01), and postoperative LOS (11.26±8.77 days vs. 11.19±8.30 days) showed no significant differences between ARE and matched groups (P>0.05). Duration (81.65±54.79 min vs. 38.89±26.09 min) and costs ($31.99±17.80 vs. $18.72±8.39) in PACU were significantly different in ARE group from those in matched group (P<0.001). Proportion of patients with prolonged stay in PACU was significantly higher in ARE group than in matched group (18.59% vs. 1.28%), with an odds ratio (after matching) of 17.58 (95% CI=4.11 to 75.10; P<0.001). The AREs that occurred during the immediate postoperative period in PACU increased the incidence rate of prolonged stay, delayed the PACU stay, and increased the costs in PACU, resulting in the need of higher levels of postoperative care than anticipated, but the postoperative LOS and inpatient healthcare costs were unchanged.


Assuntos
Anestesia/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Transtornos Respiratórios/induzido quimicamente , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Hipóxia/induzido quimicamente , Lactente , Recém-Nascido , Pacientes Internados , Tempo de Internação , Masculino , Estudos Retrospectivos
6.
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
8.
Neurosci Bull ; 35(1): 79-90, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30617765

RESUMO

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.


Assuntos
Hipertensão/metabolismo , Hipóxia/induzido quimicamente , Óxido Nítrico Sintase Tipo I/metabolismo , Núcleo Solitário/metabolismo , Animais , Barorreflexo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Óxido Nítrico Sintase Tipo I/efeitos dos fármacos , Ratos Sprague-Dawley
9.
Drug Chem Toxicol ; 42(3): 321-327, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30426789

RESUMO

Methyl isocyanate (MIC) is a highly toxic industrial chemical causing acute lethality after inhalation. The objective of this study was to determine whether alterations in hemostasis also occur in the immediate hours after exposure. Male rats were exposed to MIC (125-500 ppm) by nose-only vapor inhalation for 30 min. Arterial O2 saturation was monitored prior to exposure, and hourly thereafter. Rats were euthanized at 1, 2, 4, and 8 hr and plasma analyzed for recalcification clotting time, tissue factor (TF) activity, and protein levels. Hypoxemia, as assessed by pulse oximetry, was an early feature of MIC inhalation. In contrast to sham or low (125 ppm) concentrations, 250 and 500 ppm MIC caused significant declines in blood oxygen saturation (% SpO2) at 1 hr, which remained at deficit during the postexposure period. Commensurate with hypoxemia, plasma clotting time was significantly accelerated 1 hr after MIC inhalation (sham treatment: 955 ± 62.8 s; 125 ppm MIC: 790 ± 62 s; 250 ppm: 676 ± 28.0 s; 500 ppm: 581 ± 175 s). This procoagulant effect was transient, with no difference observed between sham and all MIC groups by 8 hr. Similarly, elevated TF activity and protein were detected in plasma 1 hr after MIC inhalation, each of which showed a progressive decline back to control levels at later timepoints. This study demonstrates that MIC inhalation resulted in hypoxemia and transient hypercoagulability of blood. Accelerated clotting occurred rapidly and was likely due to intravascular TF, which initiates the extrinsic coagulation pathway.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Isocianatos/toxicidade , Tromboplastina/metabolismo , Animais , Relação Dose-Resposta a Droga , Hipóxia/sangue , Hipóxia/induzido quimicamente , Masculino , Oxigênio/sangue , Ratos , Ratos Sprague-Dawley
10.
Biomed Pharmacother ; 109: 1688-1697, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551423

RESUMO

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl2) treatment in rats. The aim of this experiment was to explore the potential ameliorative potency of Moringa oleifera ethanolic extract (MO) against experimentally induced hypoxia on the structure and function of the rat's brain. Fifty male rats were allocated to five groups (10 rats each): a control group, a MO-treated group (400 mg/kg bw, orally), a CoCl2-treated group (40 mg/kg bw/day, orally), a prophylaxis group, and a therapeutic co-treated group. Oxidative stress biomarkers and monoamine neurotransmitter were evaluated in brain tissue. In addition, qRT-PCR for expression pattern of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. Glial fibrillary acidic protein (GFAP), apoptotic markers (BCL-2 and caspase 3) were detected immunohistochemically in brain cells. The results revealed a significantly lower concentration of GABA, monoamine neurotransmitter in hypoxic rat's brain. Moreover, an evident up-regulation of the mRNA expression of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. There was marked encephalopathy manifested by pyknotic neurons with eosinophilic cytoplasm, vacuolations and cerebral congestions in the hypoxic rat brains. Additionally, the score of neuronal expression occupied by GFAP- positive astroglia, Caspase-3 and microglial CD68 were elevated but Bcl-2 expression was found decreased in the hypoxic group than control. The endpoints of this study clearly stated that MO ethanolic extract suggestively counteracted neurotoxic impacts caused by hypoxia, particularly when it administered prior to and concurrently with CoCl2 administration.


Assuntos
Eritropoetina/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Hipóxia/metabolismo , Monoaminoxidase/biossíntese , Moringa oleifera , NF-kappa B/biossíntese , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cobalto/toxicidade , Eritropoetina/genética , Expressão Gênica , Hipóxia/induzido quimicamente , Hipóxia/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Monoaminoxidase/genética , NF-kappa B/genética , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
11.
J Anesth Hist ; 4(4): 237-239, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30558769

RESUMO

During the 19th century, patients undergoing anesthesia for surgical and dental procedures were at risk of being given hypoxic or dilute nitrous oxide on four separate occasions. Primary and secondary saturation during surgery could account for two administrations of 100% nitrous-oxide anesthesia, while both diagnostic and therapeutic doses of dilute nitrous oxide were frequently administered in mental asylums.


Assuntos
Anestesia Dentária/história , Anestesia por Inalação/história , Anestésicos Inalatórios/história , Hospitais Psiquiátricos/história , Transtornos Mentais/história , Óxido Nitroso/história , Anestesia Dentária/efeitos adversos , Anestesia Dentária/métodos , Anestesia por Inalação/efeitos adversos , Anestesia por Inalação/métodos , Anestésicos Inalatórios/uso terapêutico , Assistência Odontológica/história , Assistência Odontológica/métodos , História do Século XIX , Humanos , Hipóxia/induzido quimicamente , Hipóxia/história , Transtornos Mentais/induzido quimicamente , Óxido Nitroso/efeitos adversos , Admissão do Paciente/normas
13.
BMJ Case Rep ; 20182018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30275022

RESUMO

Hypoxic hepatitis is a rather common complication of heart, circulatory or respiratory failure. We present the case of a patient with hypoxic hepatitis in the setting of heart failure and dehydration from furosemide as a reminder of an important clinical lesson. The pathogenesis of hypoxia (especially in the case of heart failure) is explained by a two-hit mechanism in which the liver at risk of hypoxic injury by passive hepatic congestion (right heart failure) is subsequently exposed to systemic hypoperfusion, which leads to a marked and transient elevation of aminotransferases. In the case presented, the use of furosemide (at least partially) promoted the second hit because it helped to generate hypotension and splanchnic hypovolaemia and favoured hepatic hypoxia.


Assuntos
Desidratação/induzido quimicamente , Furosemida/efeitos adversos , Insuficiência Cardíaca/complicações , Hepatite/etiologia , Doença Hepática Induzida por Substâncias e Drogas , Desidratação/complicações , Desidratação/terapia , Diagnóstico Diferencial , Diuréticos/efeitos adversos , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Hepatite/metabolismo , Humanos , Hipóxia/induzido quimicamente , Hepatopatias/complicações , Hepatopatias/metabolismo , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Pathol Res Pract ; 214(11): 1804-1810, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30193773

RESUMO

The protective effect of hydrogen sulfide (H2S) against hypoxia-induced injury via anti-apoptosis is well established, but the underlying mechanism remains unclear. The present study aimed to investigate whether miR-455 participated in the H2S protection of lung epithelial cells against CoCl2-induced apoptosis by regulating endoplasmic reticulum stress (ERS)-related genes. Human lung epithelial cells BEAS-2B were subjected to hypoxia injury with or without H2S preconditioning. It was found that hypoxia injury increased apoptosis of BEAS-2B cells, down-regulated the expression of miR-455, and upregulated the expression of calreticulin (Calr). H2S preconditioning attenuated lung epithelial cells apoptosis, enhanced cell viability, up-regulated the expression of miR-455, as well as down-regulated the expression of Calr following hypoxia injury. In addition, Calr, GRP78, C/EBP homologous protein (CHOP) and Caspase-12 protein was down-regulated by the miR-455 mimic and up-regulated by the miR-455 inhibitor. These results implicate miR-455 regulated H2S protection of lung epithelial cells against hypoxia-induced apoptosis by stimulating Calr.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/genética , Células Epiteliais/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Pulmão/patologia , MicroRNAs/genética , Calreticulina/biossíntese , Linhagem Celular , Cobalto/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Hipóxia/induzido quimicamente , Hipóxia/metabolismo , Hipóxia/patologia , Pulmão/metabolismo
15.
Adv Gerontol ; 31(2): 239-245, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30080331

RESUMO

In this article materials obtained during treatment of 61 patients with acute poisoning with phenobarbital, which is part of Corvalol and Valocordin, are presented. It has already been established that phenobarbital acute poisoning in elderly and senile patients is accompanied by more frequent development of central nervous system, respiratory system (pneumonia) and cardiovascular system complications, which cause more severe clinical course and risk of an adverse outcome of acute poisoning. This research has shown that for hypoxia correction during phenobarbital acute poisoning in elderly and senile patients it is advisable to include Reamberin in the treatment regimen, which has no adverse effects on central haemodynamic parameters and effectively reduces severity of metabolic disorders.


Assuntos
Barbitúricos/envenenamento , Hipóxia/terapia , Idoso , Humanos , Hipóxia/induzido quimicamente , Envenenamento/terapia
16.
J Vis Exp ; (138)2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30124658

RESUMO

An inexpensive, laboratory-based, strain gauge valve gape monitor (SGM) was developed to monitor the valve gape behavior of bivalve molluscs in response to diel-cycling hypoxia. A Wheatstone bridge was connected to strain gauges that were attached to the shells of oysters (Crassostrea virginica). The recorded signals allowed for the opening and closing of the bivalves to be recorded continuously over two-day periods of experimentally-induced diel-cycling hypoxia and diel-cycling changes in pH. Here, we describe a protocol for developing an inexpensive strain gauge monitor and describe, in an example laboratory experiment, how we used it to measure the valve gape behavior of Eastern oysters (C. virginica), in response to diel-cycling hypoxia and cyclical changes in pH. Valve gape was measured on oysters subjected to cyclical severe hypoxic (0.6 mg/L) dissolved oxygen conditions with and without cyclical changes in pH, cyclical mild hypoxic (1.7 mg/L) conditions and normoxic (7.3 mg/L) conditions. We demonstrate that when oysters encounter repeated diel cycles, they rapidly close their shells in response to severe hypoxia and close with a time lag to mild hypoxia. When normoxia is restored, they rapidly open again. Oysters did not respond to cyclical pH conditions superimposed on diel cycling severe hypoxia. At reduced oxygen conditions, more than one third of the oysters closed simultaneously. We demonstrate that oysters respond to diel-cycling hypoxia, which must be considered when assessing the behavior of bivalves to dissolved oxygen. The valve SGM can be used to assess responses of bivalve molluscs to changes in dissolved oxygen or contaminants. Sealing techniques to better seal the valve gape strain gauges from sea water need further improvement to increase the longevity of the sensors.


Assuntos
Hipóxia/induzido quimicamente , Animais , Crassostrea , Concentração de Íons de Hidrogênio
17.
Br J Pharmacol ; 175(20): 3976-3989, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30098019

RESUMO

BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure and death. Parenteral prostaglandins (PGs), including treprostinil, a prostacyclin analogue, represent the most effective medical treatment for severe PAH. We investigated the effect of treprostinil on established severe PAH and underlying mechanisms using the rat SU5416 (SU, a VEGF receptor-2 inhibitor)-chronic hypoxia (Hx) model of PAH. EXPERIMENTAL APPROACH: Male Sprague Dawley rats were injected with SU (20 mg·kg-1 , s.c.) followed by 3 weeks of Hx (10% O2 ) to induce severe PAH. Four weeks post-SU injection, baseline right ventricular (RV) systolic pressure (RVSP) was measured, and the rats were randomized to receive vehicle or treprostinil treatment (Trep-100: 100 ng·kg-1 ·min-1 or Trep-810: 810 ng·kg-1 ·min-1 ). Following 3 weeks of treatment, haemodynamic and echocardiographic assessments were performed, and tissue samples were collected for protein expression and histological analysis. KEY RESULTS: At week 7, no difference in RVSP or RV hypertrophy was observed between vehicle and Trep-100; however, Trep-810 significantly reduced RVSP and RV hypertrophy. Trep-810 treatment significantly improved cardiac structure and function. Further, a short-term infusion of treprostinil in rats with established PAH at 4 weeks post-SU produced an acute, dose-dependent reduction in RVSP consistent with a vasodilator effect. However, chronic Trep-810 treatment did not alter media wall thickness, degree of vascular occlusion or total vessel count in the lungs. CONCLUSIONS AND IMPLICATIONS: Treprostinil exerts therapeutic benefits in PAH through decreased vascular resistance and improved cardiac structure and function; however, treprostinil treatment does not have direct impact vascular remodelling.


Assuntos
Anti-Hipertensivos/uso terapêutico , Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Vasodilatadores/uso terapêutico , Inibidores da Angiogênese , Animais , Epoprostenol/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Hipóxia/induzido quimicamente , Hipóxia/tratamento farmacológico , Hipóxia/fisiopatologia , Indóis , Masculino , Inibidores de Proteínas Quinases , Pirróis , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Remodelação Vascular/fisiologia , Função Ventricular Direita/efeitos dos fármacos
18.
J Surg Orthop Adv ; 27(2): 148-154, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30084824

RESUMO

Postoperative analgesia after primary total knee arthroplasty (TKA) and revision knee arthroplasty (RKA) can be reliant on the use of opioids and may lead to opioid-related adverse events (ORAEs). This study evaluated the risk of ORAEs following TKA and RKA using the 5% Medicare claims (2010-2013) database. There were 41,702 TKA and 3817 RKA patients who met the inclusion criteria. At 90 days, respiratory complications were the most common complication (TKA: 6.12%; RKA: 8.01%), followed by postoperative nausea and vomiting (TKA: 2.86%; RKA: 3.95%), and urinary retention complications (TKA: 2.79%; RKA: 3.20%). For TKA, risk factors for respiratory complications included older age, lower socioeconomic status, more comorbidities, obesity, chronic obstructive pulmonary disease, white race, and patients in the Midwest and West (vs. South) (p 002). The average Medicare payment for treating complications within 90 days of a TKA was $6206 and $6222 following RKA. Awareness risks for ORAEs in select patients can assist in developing a multimodal postoperative pain control and patient education protocols. (Journal of Surgical Orthopaedic Advances 27(2):148-154, 2018).


Assuntos
Analgésicos Opioides/efeitos adversos , Artroplastia do Joelho , Dor Pós-Operatória/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Asfixia/induzido quimicamente , Confusão/induzido quimicamente , Constipação Intestinal/induzido quimicamente , Delírio/induzido quimicamente , Exantema/induzido quimicamente , Feminino , Humanos , Hipóxia/induzido quimicamente , Pseudo-Obstrução Intestinal/induzido quimicamente , Masculino , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Prurido/induzido quimicamente , Taxa Respiratória/efeitos dos fármacos
19.
Physiol Res ; 67(5): 721-728, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30044117

RESUMO

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.


Assuntos
Anestesia Geral , Anestésicos Gerais/farmacologia , Fenômenos Cronobiológicos/fisiologia , Ketamina/farmacologia , Pentobarbital/farmacologia , Tiletamina/farmacologia , Zolazepam/farmacologia , Anestesia Geral/efeitos adversos , Anestesia Geral/tendências , Anestésicos Gerais/efeitos adversos , Anestésicos Gerais/sangue , Animais , Gasometria/métodos , Fenômenos Cronobiológicos/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Hipercapnia/sangue , Hipercapnia/induzido quimicamente , Hipóxia/sangue , Hipóxia/induzido quimicamente , Ketamina/efeitos adversos , Pentobarbital/efeitos adversos , Ratos , Ratos Wistar , Tiletamina/efeitos adversos , Zolazepam/efeitos adversos
20.
Vet Anaesth Analg ; 45(4): 502-509, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29891211

RESUMO

OBJECTIVE: To evaluate clinical and physiological responses in moose to thiafentanil administration for immobilization. STUDY DESIGN: Cross-sectional clinical study. ANIMALS: Eleven (six males and five females) free-ranging adult moose (Alces alces). METHODS: Each moose was darted from a helicopter with 7.5 mg thiafentanil during March 2014 in northern Sweden. Physiological evaluation included vital signs and blood gases. Arterial blood was collected after induction and again after 10 minutes of intranasal oxygen administration and analyzed immediately with an i-STAT analyzer. A total of 10 mg naltrexone per milligram of thiafentanil was administered to all animals for reversal. Data were analyzed using descriptive statistics. RESULTS: All moose were sufficiently immobilized with a single dart injection. Induction occurred within 3 minutes in 10 of 11 moose. One individual became recumbent while crossing a river and naltrexone was immediately administered. Animals maintained sternal recumbency with their head raised and vital signs were stable. Nine of 10 moose were hypoxemic before oxygen administration, with seven becoming markedly hypoxemic [partial pressure of arterial oxygen (PaO2) between 40 and 59 mmHg (5.3-7.9 kPa)]. The PaO2 increased significantly between samples, but six moose remained hypoxemic despite therapy. Hypercapnia was seen in all moose, with eight having marked hypercapnia [partial pressure of arterial carbon dioxide (PaCO2) > 60 mmHg (>8.0 kPa)]. All moose were acidemic, with nine showing marked acidemia (pH < 7.20). The pH increased significantly with time and lactate decreased. Recoveries were rapid and uneventful, and all moose were living 6 months after capture. CONCLUSIONS: Thiafentanil provided rapid and sufficient immobilization of moose and its effects were rapidly reversed with naltrexone. As with other opioids, moose showed hypoxemia and varying degrees of respiratory and metabolic acidosis. Arterial oxygenation of moose improved following intranasal oxygen, but hypoxemia was not fully resolved despite therapy. CLINICAL RELEVANCE: Thiafentanil (7.5 mg per adult) is effective for immobilization of free-ranging moose. Supplemental oxygen may be of benefit when using this regimen; however, further investigation is required to confirm these results.


Assuntos
Cervos , Fentanila/análogos & derivados , Hipnóticos e Sedativos , Imobilização/veterinária , Animais , Animais Selvagens , Gasometria/veterinária , Temperatura Corporal/efeitos dos fármacos , Dióxido de Carbono/sangue , Estudos Transversais , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Fentanila/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Hipóxia/induzido quimicamente , Hipóxia/veterinária , Imobilização/efeitos adversos , Imobilização/métodos , Injeções Intramusculares/métodos , Injeções Intramusculares/veterinária , Masculino , Oxigênio/sangue , Taxa Respiratória/efeitos dos fármacos , Suécia
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