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1.
Am Heart J ; 225: 78-87, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32474207

RESUMO

BACKGROUND: The severity of aortic coarctation (CoA) may be underestimated during cardiac catheterization. We aimed to investigate whether epinephrine stress testing improves clinical decision making and outcome in CoA. METHODS: We retrospectively evaluated CoA patients >50 kg with a peak systolic gradient (PSG) ≤20 mm Hg during cardiac catheterization who underwent epinephrine stress testing. Subsequent interventional management (stenting or balloon dilatation), complications, and medium-term clinical outcome were assessed. RESULTS: Fifty CoA patients underwent cardiac catheterization with epinephrine stress testing. Patients with a high epinephrine PSG (>20 mm Hg; n = 24) were younger and more likely to have a hypertensive response to exercise compared to patients with a low epinephrine PSG (≤20 mm Hg; n = 26). In total, 21 patients (88%) with a high epinephrine PSG underwent intervention, and 20 patients (77%) with a low epinephrine PSG were treated conservatively. After a mean follow-up of 25 ±â€¯18 months, there was a lower prevalence of hypertension in patients with a high epinephrine PSG who underwent intervention compared to patients with a low epinephrine PSG treated conservatively (19% vs. 76%; P = .001). In a multivariate model, intervention was independently associated with a 14.3-mm Hg reduction in systolic blood pressure (P = .001) and a decrease in the use of antihypertensive agents. CONCLUSIONS: In CoA patients with a low baseline PSG but high epinephrine PSG, percutaneous intervention is associated with a substantial reduction in systemic blood pressure and the use of antihypertensive medication. Accordingly, epinephrine stress testing may be a useful addition in the evaluation of CoA.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Coartação Aórtica/cirurgia , Pressão Sanguínea/efeitos dos fármacos , Cateterismo Cardíaco , Epinefrina/farmacologia , Adolescente , Adulto , Coartação Aórtica/diagnóstico , Coartação Aórtica/fisiopatologia , Tomada de Decisão Clínica , Teste de Esforço/métodos , Feminino , Humanos , Hipertensão/etiologia , Masculino , Estudos Retrospectivos , Sístole/fisiologia , Adulto Jovem
2.
PLoS One ; 15(5): e0233558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469977

RESUMO

Eye temperature measured using infrared thermography (IRT) can be used as a non-invasive measure of autonomic nervous system (ANS) activity in cattle. The objective of this study was to evaluate if changes in eye temperature (measured using IRT) can be used to non-invasively measure ANS activity in sheep. Twenty, 2 to 4-year-old, Romney ewes were randomly assigned to receive either epinephrine (EPI) or physiological saline (SAL) for 5 min administered via jugular catheter (n = 10 ewes/treatment). Eye temperature (°C) was recorded continuously using IRT for approximately 25 min before and 20 min after the start of infusion. Heart rate and heart rate variability, measured using the root mean square of successive differences (RMSSD) and the standard deviation of all inter-beat intervals (SDNN), were recorded for 5 min before and up to 10 min after the start of infusion. Blood samples were taken before and after the infusion period to measure plasma epinephrine, norepinephrine, cortisol and packed cell volume (PCV) concentrations. During the infusion period, maximum eye temperature was on average higher (P<0.05) in sheep that received epinephrine than those that received saline. On average, heart rate was higher (SAL: 87.5 beats/min, EPI: 123.2 beats/min, SED = 7.07 beats/min; P<0.05), and RMSSD (SAL: 55.3 ms, EPI: 17.3 ms, SED = 14.18 ms) and SDNN (SAL: 54.3 ms, EPI: 21.5 ms, SED = 10.00 ms) lower (P<0.05) in ewes during the 5 min post-infusion period compared with ewes that received saline. An infusion of epinephrine resulted in higher geometric mean epinephrine (P<0.05) and cortisol (P<0.05) but not norepinephrine (P>0.05) concentrations in ewes compared to an infusion of saline. PCV concentrations were higher (P<0.001) by 7 ± 1.0% (mean±SED) in ewes after an epinephrine infusion. These results suggest that heart rate variability is a sensitive, non-invasive method that can be used to measure ANS activity in sheep, whereas change in eye temperature measured using IRT is a less sensitive method.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Temperatura Corporal/efeitos dos fármacos , Ovinos/fisiologia , Termografia/métodos , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Epinefrina/farmacologia , Olho , Feminino , Frequência Cardíaca , Raios Infravermelhos
3.
PLoS One ; 15(5): e0230516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453770

RESUMO

Teaching practicals for receptor physiology/pharmacology in medical and veterinary schools have involved the use of in vitro experiments using tissues from laboratory animals, which have been killed for isolated vascular strip or ring preparations. However, the use of scavenged tissues has been advocated to reduce animal use. Utilising discarded tissues from routine surgical procedures, such as canine neutering, has not previously been investigated. Canine testicular and uterine tissues (discarded tissues) were obtained from routine neutering procedures performed by the veterinary team at a local animal neutering clinic for stray dogs. Rings of uterine and testicular artery were dissected and mounted on a Mulvany-Halpern wire myograph in order to characterize the adrenergic and serotonergic receptors mediating vasoconstriction. Cumulative contractile concentration-response curves were constructed for the alpha adrenoceptor agonists epinephrine (α1 and α2 receptors), phenylephrine (α1 selective) and UK14304 (α2 selective). Pre-treatment with the α1-selective antagonist, prazosin, was also investigated. The response to serotonin (5-HT) receptor agonists were also investigated, including 5-HT (acting at both 5-HT1 and 5-HT2 receptors), 5-carboxamidotryptamine (5-CT; 5-HT1 selective) and α-methyl 5-HT (5-HT2 selective). A contractile response was observed in both canine uterine and testicular arteries to epinephrine and phenylephrine, and prazosin caused a dose-dependent parallel rightward shift in the phenylephrine dose-response curve (pA2 values of 7.97 and 8.39, respectively). UK14304 caused a contractile response in canine testicular arteries but very little appreciable contractile response in uterine arteries. The maximum responses produced by the uterine arteries to 5-HT was significantly lower than those of the testicular arteries. In the testicular artery, the 5-HT2 receptor selective agonist, α-methyl 5-HT, produced a similar contractile response to 5-HT but the administration of 5-CT failed to produce a response in either the testicular or uterine artery segments. These results validate the use of discarded tissue from routine canine neutering procedures as a useful source of vascular tissue for pharmacological teaching, for characterizing alpha and 5-HT receptor contractile responses.


Assuntos
Contração Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Ensino , Artéria Uterina/fisiologia , Animais , Animais de Laboratório , Cães , Epinefrina/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/anatomia & histologia , Norepinefrina/farmacologia , Artéria Uterina/anatomia & histologia
4.
Am J Physiol Endocrinol Metab ; 318(5): E779-E790, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32208001

RESUMO

Glucagon's effect on hepatic glucose production (HGP), under hyperglycemic conditions, is time dependent such that after an initial burst of HGP, it slowly wanes. It is not known whether this is also the case under hypoglycemic conditions, where an increase in HGP is essential. This question was addressed using adrenalectomized dogs to avoid the confounding effects of other counterregulatory hormones. During the study, infusions of epinephrine and cortisol were given to maintain basal levels. Somatostatin and insulin (800 µU·kg-1·min-1) were infused to induce hypoglycemia. After 30 min, glucagon was infused at a basal rate (1 ng·kg-1·min-1, baGGN group, n = 5 dogs) or a rate eightfold basal (8 ng·kg-1·min-1, hiGGN group, n = 5 dogs) for 4 h. Glucose was infused to match the arterial glucose levels between groups (≈50 mg/dL). Our data showed that glucagon has a biphasic effect on the liver despite hypoglycemia. Hyperglucagonemia stimulated a rapid, transient peak in HGP (4-fold basal production) over ~60 min, which was followed by a slow reduction in HGP to a rate 1.5-fold basal. During the last 2 h of the experiment, hiGGN stimulated glucose production at a rate fivefold greater than baGGN (2.5 vs. 0.5 mg·kg-1·min-1, respectively), indicating a sustained effect of the hormone. Of note, the hypoglycemia-induced rises in norepinephrine and glycerol were smaller in hiGGN compared with the baGGN group despite identical hypoglycemia. This finding suggests that there is reciprocity between glucagon and the sympathetic nervous system such that when glucagon is increased, the sympathetic nervous response to hypoglycemia is downregulated.


Assuntos
Glucagon/farmacocinética , Gluconeogênese/efeitos dos fármacos , Hipoglicemia/metabolismo , Fígado/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Adrenalectomia , Animais , Cães , Epinefrina/farmacologia , Feminino , Hidrocortisona/farmacologia , Hipoglicemia/induzido quimicamente , Insulina , Fígado/metabolismo , Masculino , Somatostatina , Sistema Nervoso Simpático/metabolismo
5.
Arq Bras Cardiol ; 114(2): 295-303, 2020 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32215501

RESUMO

BACKGROUND: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. OBJECTIVE: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. METHOD: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. RESULTS: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. CONCLUSIONS: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.


Assuntos
Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Epinefrina/farmacologia , Felipressina/farmacologia , Poluição por Fumaça de Tabaco/efeitos adversos , Vasoconstritores/farmacologia , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipotensão , Masculino , Ratos Wistar , Fatores de Tempo , Vasodilatação/efeitos dos fármacos
6.
J Craniofac Surg ; 31(3): 791-793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32028367

RESUMO

Plastic surgeons commonly administer subcutaneous epinephrine to reduce intraoperative blood loss. The authors hypothesized that there are safe and effective concentration of epinephrine for vasoconstriction and their durations. The aim of this study is to summarize the existing literatures for the usage of epinephrine mixed with lidocaine in plastic surgical field.In 1903, Braun reported that adrenaline prolonged the local anesthetic effects of cocaine. The Parke-Davis Company began selling cocaine with adrenaline, as well as combining adrenaline with new synthetic local anesthetics.Based on a review of the literature, concentrations between 1:50,000 and 1:400,000 are equally effective and provide superior vasoconstriction compared with more dilute solutions. If epinephrine is further diluted, its onset and time to peak serum concentration are delayed, and its duration of action is shortened. When lidocaine is used without epinephrine, duration of anesthesia is shortened reverse proportionally to the lidocaine concentration. When lidocaine is used with epinephrine, duration of anesthesia is prolonged proportionally to the lidocaine concentration. With slow injection rate in the soft tissue, the maximum safe dose of lidocaine is approximately 3 mg/kg plain and 7 mg/kg when mixed with epinephrine. Lidocaine may protect the myocardium because of its antiarrhythmic activity, which is the rationale for infiltrating lidocaine mixed with epinephrine in general anesthesia.In plastic surgery, subcutaneous infiltration of epinephrine-lidocaine solution is performed to reduce intraoperative blood loss. Even in general anesthesia, infiltrating lidocaine mixed with epinephrine may protect the myocardium because of its antiarrhythmic activity.


Assuntos
Anestésicos Locais/farmacologia , Epinefrina/farmacologia , Lidocaína/farmacologia , Humanos , Procedimentos Cirúrgicos Reconstrutivos , Cirurgia Plástica , Vasoconstrição
7.
Diabetes ; 69(5): 882-892, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32005706

RESUMO

Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fasted state. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering drugs that act primarily in the kidney, but some reports have described direct effects of SGLT2i on α-cells to stimulate glucagon secretion. Interestingly, SGLT2 inhibition also results in increased endogenous glucose production and ketone production, features common to glucagon action. Here, we directly test the ketogenic role of glucagon in mice, demonstrating that neither fasting- nor SGLT2i-induced ketosis is altered by interruption of glucagon signaling. Moreover, any effect of glucagon to stimulate ketogenesis is severely limited by its insulinotropic actions. Collectively, our data suggest that fasting-associated ketosis and the ketogenic effects of SGLT2 inhibitors occur almost entirely independent of glucagon.


Assuntos
Compostos Benzidrílicos/farmacologia , Privação de Alimentos , Glucagon/metabolismo , Glucosídeos/farmacologia , Insulina/sangue , Transportador 2 de Glucose-Sódio/metabolismo , Animais , Glicemia , Epinefrina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Insulina/metabolismo , Lipólise/efeitos dos fármacos , Camundongos , Transportador 2 de Glucose-Sódio/genética , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
8.
Cardiovasc Eng Technol ; 11(2): 205-218, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31916039

RESUMO

PURPOSE: The objective of this study was to bioengineer 3D patches from cardiac myocytes that have been reprogrammed from human adipogenic mesenchymal stem cells (hADMSCs). METHODS: Human adipogenic mesenchymal stem cells (hADMSCs) were reprogrammed to form cardiac myocytes using transcription factors ETS2 and MESP1. Reprogrammed cardiac myocytes were cultured in a fibrin gel to bioengineer 3D patch patches. The effect of initial plating density (1-25 million cells per patch), time (28-day culture period) and treatment with 1 µM isoproterenol and 1 µM epinephrine were evaluated. RESULTS: 3D patches were fabricated using cardiac myocytes that have been reprogrammed from hADMSCs. Based on optimization studies, it was determined that 10 million cells were needed to bioengineer a single patch, that measured 2 × 2 cm2. Furthermore, 3D patches fabricated 10 million cells were stable in culture for up to 28 days. Treatment of 3D patches with 1 µM isoproterenol and 1 µM epinephrine resulted in an increase in the electrical properties, as measured by electrical impulse amplitude and frequency. An increase in the expression of mTOR, KCNV1, GJA5, KCNJ16, CTNNT2, KCNV2, MYO3, FOXO1 and KCND2 was noted in response to treatment of 3D patches with isoproterenol and epinephrine. CONCLUSION: Based on the results of this study, there is evidence to support the successful fabrication of a highly functional 3D patches with measurable electrical activity using cardiac myocytes reprogrammed from hADMSCs. 3D patches fabricated using optimal conductions described in this study can be used to improve the functional properties of failing hearts. Predominantly, in case of the infarcted hearts with partial loss of electrical activity, the electrical properties of the 3D patches may restore the electrical activity of the heart.


Assuntos
Adipogenia , Técnicas de Reprogramação Celular , Reprogramação Celular , Insuficiência Cardíaca/cirurgia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Miócitos Cardíacos/transplante , Engenharia Tecidual , Agonistas Adrenérgicos/farmacologia , Células Cultivadas , Condutividade Elétrica , Epinefrina/farmacologia , Fibrina/metabolismo , Regulação da Expressão Gênica , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Isoproterenol/farmacologia , Potenciais da Membrana , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fatores de Tempo
9.
Int Forum Allergy Rhinol ; 10(1): 114-120, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899857

RESUMO

BACKGROUND: The objective of this study is to characterize changes in hemodynamics, pain, and anxiety during office-based endoscopic sinus procedures performed under local anesthesia. METHODS: We conducted a prospective study of adults undergoing in-office endoscopic sinus procedures under local anesthesia. Patients with American Society of Anesthesiologists (ASA) Physical Status Classification System class 1 or 2 were included. Anesthesia was administered by topical 4% lidocaine/oxymetazoline and submucosal injection of 1% lidocaine/1:200,000 epinephrine. Vital signs and pain were measured at baseline, postinjection, and 5-minute intervals throughout the procedure. Anxiety levels were scored using the State-Trait Anxiety Inventory (STAI). Univariate and multivariate regression analyses were performed to identify factors significantly associated with changes in each hemodynamic metric. RESULTS: Twenty-five patients were studied. This cohort was 52% male, mean age of 57.8 ± 14.4 years, and Charlson Comorbidity Index (CCI) median of 2. Mean procedure duration was 25.0 ± 10.3 minutes. Mean maximal increase in systolic blood pressure (SBP) was 24.6 ± 17.8 mmHg from baseline. Mean maximal heart rate increase was 22.8 ± 10.8 beats per minute (bpm) from baseline. In multivariate regression analysis, when accounting for patient age, cardiac comorbidity, CCI, and ASA, older age was significantly associated with an increase of >20 mmHg in SBP (p = 0.043). Mean pain score during procedures was 1.5 ± 1.3 with a mean maximum of 4.0 ± 2.6. STAI anxiety scores did not change significantly from preprocedure to postprocedure (32.8 ± 11.6 to 31.0 ± 12.6, p = 0.46). No medical complications occurred. CONCLUSION: Although patients appear to tolerate office procedures well, providers should recognize the potential for significant fluctuations in blood pressure during the procedure, especially in older patients.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Anestesia Local , Hemodinâmica/efeitos dos fármacos , Seios Paranasais/cirurgia , Adulto , Fatores Etários , Idoso , Pressão Sanguínea/efeitos dos fármacos , Endoscopia , Epinefrina/administração & dosagem , Epinefrina/farmacologia , Feminino , Humanos , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Duração da Cirurgia , Medição da Dor , Estudos Prospectivos
10.
Eur J Pharmacol ; 866: 172798, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31738933

RESUMO

Ticagrelor, an antagonist of the platelet adenosine diphosphate (ADP)-P2Y12 receptor is recommended for patients with acute coronary syndromes. However, ticagrelor exposes to a risk of bleeding, the management of which is challenging because platelet transfusion is ineffective, and no antidote is yet available. We hypothesized that the vasopressor drug epinephrine could counter the antiplatelet effects of ticagrelor and restore platelet functions. We assessed in vitro the efficiency of epinephrine in restoring platelet aggregation inhibited by ticagrelor and investigated the underlying mechanisms. Washed platelet aggregation and secretion were measured upon stimulation by epinephrine alone or in combination with ADP, in the presence or absence of ticagrelor. Mechanistic investigations used P2Y1 and phosphoinositide 3-kinase (PI3K) inhibitors and included vasodilator-stimulated phosphoprotein (VASP) and Akt phosphorylation assays as well as measurement of Ca2+ mobilisation. We found that epinephrine restored ADP-induced platelet aggregation, but not dense granule release. Epinephrine alone failed to induce aggregation whereas it fully induced VASP dephosphorylation and Akt phosphorylation regardless of the presence of ticagrelor. In the presence of ticagrelor, blockage of the P2Y1 receptor prevented restoration of platelet aggregation by the combination of epinephrine and ADP, as well as intracellular Ca2+ mobilisation. In combination with ADP, epinephrine induced platelet aggregation of ticagrelor-treated platelets through inhibition of the cAMP pathway and activation of the PI3K pathway, thus enabling the P2Y1 receptor signalling and subsequent Ca2+ mobilisation. This proof-of-concept study needs to be challenged in vivo for the management of bleeding in ticagrelor-treated patients.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Epinefrina/farmacologia , Ticagrelor/farmacologia , Plaquetas/citologia , Moléculas de Adesão Celular/metabolismo , Humanos , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Receptores Purinérgicos P2Y1/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Int J Mol Sci ; 20(22)2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31717935

RESUMO

BACKGROUND: Considering the positive or negative potential effects of adipocytes, depending on their lipid composition, on breast tumor progression, it is important to evaluate whether adipose tissue (AT) harvesting procedures, including epinephrine infiltration, may influence breast cancer progression. METHODS: Culture medium conditioned with epinephrine-infiltrated adipose tissue was tested on human Michigan Cancer Foundation-7 (MCF7) breast cancer cells, cultured in monolayer or in oncospheres. Lipid composition was evaluated depending on epinephrine-infiltration for five patients. Epinephrine-infiltrated adipose tissue (EI-AT) or corresponding conditioned medium (EI-CM) were injected into orthotopic breast carcinoma induced in athymic mouse. RESULTS: EI-CM significantly increased the proliferation rate of MCF7 cells Moreover EI-CM induced an output of the quiescent state of MCF7 cells, but it could be either an activator or inhibitor of the epithelial mesenchymal transition as indicated by gene expression changes. EI-CM presented a significantly higher lipid total weight compared with the conditioned medium obtained from non-infiltrated-AT of paired-patients. In vivo, neither the EI-CM or EI-AT injection significantly promoted MCF7-induced tumor growth. CONCLUSIONS: Even though conditioned media are widely used to mimic the secretome of cells or tissues, they may produce different effects on tumor progression, which may explain some of the discrepancy observed between in vitro, preclinical and clinical data using AT samples.


Assuntos
Tecido Adiposo/metabolismo , Proliferação de Células/efeitos dos fármacos , Epinefrina/farmacologia , Metabolismo dos Lipídeos , Neoplasias Mamárias Experimentais/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Meios de Cultivo Condicionados/farmacologia , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/normas
12.
J Med Life ; 12(3): 296-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666834

RESUMO

During menstruation, endometrial hemostasis is achieved by platelet aggregation, fibrin deposition, and thrombus formation that interact with local endocrine and immunological factors which cause termination of menstrual bleeding. Interactions between steroidal sex hormones and platelet functions are not well understood. The aim of this study was to evaluate the effect of platelet function during the menstrual cycle and luteal phase in women of reproductive age. The cross-sectional study on women of reproductive age included 44 healthy women. Platelet function was assessed by PFA-100TM analyzer with collagen/epinephrine and collagen/ADP cartridges during the menstrual cycle and luteal phase. There were no significant differences in platelet function between menstruation and ovulatory phase. Platelet activity in Arab collagen/epinephrine cartridge increased during menstruation compared to non-Arab ethnic subjects and no significant differences in platelet function were found when using collagen/ADP cartridge. This study suggested modulation in platelet functions during menstruation and luteal phase in women of reproductive age. Further studies, including a large number of subjects, platelet genetic and progesterone factors change in platelet clotting associated to menstrual cycle should be conducted.


Assuntos
Plaquetas/fisiologia , Menstruação/fisiologia , Ovulação/fisiologia , Adulto , Colágeno/farmacologia , Estudos Transversais , Epinefrina/farmacologia , Feminino , Humanos , Pré-Menopausa/fisiologia
13.
Anaesthesia ; 74(11): 1389-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389614

RESUMO

We evaluated the effect of adrenaline on human skin microcirculation (nutritive and sub-papillary) and systemic cardiovascular variables after it was added to lidocaine in infraclavicular brachial plexus blocks. Twelve healthy, non-smoking male volunteers were included, each attending two study sessions 2 weeks apart, and they were studied using a crossover design. In both sessions, they received an ultrasound-guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine, 15 mg.ml-1 with or without adrenaline 5 µg.ml-1 . Microcirculation was assessed by laser Doppler fluxmetry (sub-papillary blood flow), capillary video microscopy (nutritive blood flow) and continuous temperature measurements. Heart rate and arterial pressure were recorded continuously and non-invasively. Median (IQR [range]) sub-papillary blood flow increased substantially 30 min after the brachial plexus block, from 8.5 (4.4-13.5 [2.9-28.2]) to 162.7 (111.0-197.8 [9.5-206.7]) arbitrary units with adrenaline (p = 0.017), and from 6.9 (5.3-28.5 [1.8-42.1] to 133.7 (16.5-216.7 [1.0-445.0] arbitrary units without adrenaline (p = 0.036). Nutritive blood flow (functional capillary density, capillaries.mm-2 , measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was used as adjuvant, from median (IQR [range]) 45 (36-52 [26-59]) to 38 (29-41 [26-42]), p = 0.028, whereas no significant change occurred without adrenaline. Median finger skin temperature (°C) increased by 44% (data pooled) with no significant differences between the groups. No significant changes were found in the systemic cardiovascular variables with or without adrenaline. We conclude that lidocaine infraclavicular brachial plexus blocks caused an increase in skin sub-papillary blood flow. The addition of adrenaline produced stronger and longer lasting blocks, but decreased the nutritive blood flow.


Assuntos
Anestésicos Locais/farmacologia , Bloqueio do Plexo Braquial/métodos , Epinefrina/farmacologia , Hemodinâmica/efeitos dos fármacos , Lidocaína/farmacologia , Microcirculação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Hemodinâmica/fisiologia , Humanos , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Ultrassonografia de Intervenção/métodos , Adulto Jovem
14.
PLoS One ; 14(8): e0220987, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393950

RESUMO

We showed previously an epinephrine-induced inhibition of the Na+/K+ ATPase in Caco-2 cells mediated via PGE2. This work is an attempt to further elucidate mediators downstream of PGE2 and involved in the observed inhibitory effect. The activity of the Na+/K+ ATPase was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of ouabain, a specific inhibitor of the enzyme. Changes in the protein expression of the Na+/K+ ATPase were investigated by western blot analysis which revealed a significant decrease in the abundance of the ATPase in plasma membranes. Treating the cells with epinephrine or PGE2 in presence of SC19220, a blocker of EP1 receptors abolished completely the effect of the hormone and the prostaglandin while the effect was maintained unaltered in presence of antagonists to all other receptors. Treatment with calphostin C, PTIO, ODQ or KT5823, respective inhibitors of PKC, NO, soluble guanylate cyclase and PKG, abrogated completely the effect of epinephrine and PGE2, suggesting an involvement of these mediators. A significant inhibition of the ATPase was observed when cells were treated with PMA, an activator of PKC or with 8-Br-cGMP, a cell permeable cGMP analogue. PMA did reduce the protein expression of IκB, as shown by western blot analysis, and its effect on the ATPase was not manifested in presence of an inhibitor of NF-κB while that of SNAP, a nitric oxide donor, was not affected. The results infer that NF-κB is downstream PKC and upstream NO. The data support a pathway in which epinephrine induces the production of PGE2 which binds to EP1 receptors and activates PKC and NF-κB leading to NO synthesis. The latter activates soluble guanylate cyclase resulting in cGMP production and activation of PKG which through direct or indirect phosphorylation inhibits the Na+/K+ ATPase by inducing its internalization.


Assuntos
Dinoprostona/farmacologia , Epinefrina/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Proteína Quinase C/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Células CACO-2 , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Ativação Enzimática/efeitos dos fármacos , Humanos , Receptores de Prostaglandina E Subtipo EP1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Guanilil Ciclase Solúvel/metabolismo
15.
Int Wound J ; 16(5): 1190-1194, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407479

RESUMO

The most commonly used local anaesthetics (LAs) for postoperative analgesia and surgical anaesthesia are lidocaine and bupivacaine. Adrenaline is a vasopressor agent, which is widely used in anaesthesia for many purposes. This study aims to determine the antibacterial efficacy of lidocaine, mupirocin, adrenaline, and lidocaine + adrenaline combination. In our study, the in vitro antimicrobial effect of 1 mL of sterile saline, 20 mg/mL mupirocin, 20 mg/mL lidocaine, 1 mg/mL adrenaline, and 20 mg/mL lidocaine and adrenaline were tested against Staphylococcus aureus American-type culture collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922, classified as Group C (control), Group M (mupirocin), Group L (lidocaine), Group A (adrenaline), and Group LA (lidocaine+adrenaline), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, and E. coli ATCC 25922 were cultured on Mueller-Hinton agar (Oxoid, UK) plates for 18 to 24 hours at 37°C. Colonies from these plates were suspended in sterile saline, and a 0.5 McFarland turbidity standard suspension (corresponding to 1.5 × 108 CFU/mL) of each isolate was prepared. In terms of inhibition zone diameters, S. aureus ATCC 29213 values obtained after 12 and 24 hours of incubation were significantly different between groups (P < .001). According to inhibition zone diameters, Group M > Group LA > Group L > Group C = Group A. P. Aeruginosa ATCC 27853 values obtained after 12 and 24 hours of incubation were significantly different between groups (P < .001). According to inhibition zone diameters, Group M > Group LA > Group L = Group C = Group A. E. coli ATCC 25922 values obtained after 12 and 24 hours of incubation were significantly different between groups (P < .001). According to inhibition zone diameters, Group M > Group LA > Group L > Group C = Group A. It is known that LAs have antimicrobial effect potential in addition to their anaesthetic, analgesic, antiarrhythmic, and anti-inflammatory effects. There are also studies showing the antimicrobial effects of vasopressor agents, which are frequently used, particularly in intensive care unit (ICUs). However, it has been observed in the present study that adrenaline alone did not have any antimicrobial effect. Adrenaline, when used in combination with lidocaine, provides a stronger and broad-spectrum antimicrobial activity, suggesting that its combined use in proper indications will be clinically significant. Because the prevention and treatment of wound infections make a positive contribution to wound healing, the potential of antimicrobial effect of LAs can provide successful results in the prevention and treatment of ICU and wound infections. Thus, an important contribution can be made in terms of reducing the costs of antibacterial treatment and reducing morbidity.


Assuntos
Epinefrina/farmacologia , Escherichia coli/efeitos dos fármacos , Lidocaína/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e Especificidade
16.
Hemoglobin ; 43(2): 88-94, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31290363

RESUMO

Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.


Assuntos
Dor Aguda/etiologia , Anemia Falciforme/patologia , AMP Cíclico/análise , Eritrócitos/química , Adulto , Anemia Falciforme/complicações , Estudos de Casos e Controles , Epinefrina/farmacologia , Feminino , Hemoglobina Fetal/farmacologia , Humanos , Índia , Masculino
17.
Anticancer Res ; 39(7): 3519-3529, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262876

RESUMO

BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Catalase/farmacologia , Células Cultivadas , Criança , Clonidina/farmacologia , Fragmentação do DNA , Dexmedetomidina/farmacologia , Epinefrina/farmacologia , Humanos , Isoproterenol/farmacologia , Fenilefrina/farmacologia , Superóxido Dismutase/farmacologia
18.
Biomed Res Int ; 2019: 6539050, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309111

RESUMO

Objective: To determine whether the administration of intra-arrest cyclosporine (CCY) and methylprednisolone (MP) preserves left ventricular ejection fraction (LVEF) and cardiac output (CO) after return of spontaneous circulation (ROSC). Methods: Eleven, 25-30kg female swine were randomized to receive 10mg/kg CCY + 40mg MP or placebo, anesthetized and given a transthoracic shock to induce ventricular fibrillation. After 8 minutes, standard CPR was started. After two additional minutes, the experimental agent was administered. Animals with ROSC were supported for up to 12h with norepinephrine as needed. Echocardiography was performed at baseline, and 1, 2, 6 and 12h post-ROSC. Analysis was performed using generalized estimating equations (GEE) after downsampling continuously sampled data to 5 minute epochs. Results: Eight animals (64%) achieved ROSC after a median of 7 [IQR 5-13] min of CPR, 2 [ IQR 1-3] doses of epinephrine and 2 [IQR 1-5] defibrillation shocks. Animals receiving CCY+MP had higher post ROSC MAP (GEE coefficient -10.2, P = <0.01), but reduced cardiac output (GEE coefficient 0.8, P = <0.01) compared to placebo. There was no difference in LVEF or vasopressor use between arms. Conclusions: Intra-arrest cyclosporine and methylprednisolone decreased post-arrest cardiac output and increased mean arterial pressure without affecting left ventricular ejection fraction.


Assuntos
Cardiomiopatias/tratamento farmacológico , Ciclosporina/farmacologia , Parada Cardíaca/tratamento farmacológico , Metilprednisolona/farmacologia , Animais , Débito Cardíaco/efeitos dos fármacos , Reanimação Cardiopulmonar/métodos , Ecocardiografia/métodos , Cardioversão Elétrica/métodos , Epinefrina/farmacologia , Feminino , Ventrículos do Coração/efeitos dos fármacos , Suínos , Vasoconstritores/farmacologia , Fibrilação Ventricular/tratamento farmacológico
19.
J Pharmacol Sci ; 140(2): 205-209, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262461

RESUMO

The cardio-ankle vascular index (CAVI) has been established as a stiffness indicator from thoracic aorta to tibial arteries. To better understand physiological regulatory factors for the arterial stiffness, we assessed effects of angiotensin II and adrenaline on the CAVI in anesthetized rabbits. A hypertensive dose of angiotensin II (300 ng/kg, i.v.) increased the CAVI as well as the heart-ankle pulse wave velocity (haPWV). On the other hand, although a hypertensive dose of adrenaline (1000 ng/kg, i.v.) increased the haPWV, it did not affect the CAVI. These results suggest that angiotensin II may act as a regulatory factor for arterial stiffness.


Assuntos
Angiotensina II/farmacologia , Índice Vascular Coração-Tornozelo , Monitorização Fisiológica , Rigidez Vascular/efeitos dos fármacos , Vasoconstritores/farmacologia , Anestesia , Angiotensina II/fisiologia , Animais , Relação Dose-Resposta a Droga , Epinefrina/farmacologia , Masculino , Análise de Onda de Pulso , Coelhos
20.
Rev. cient. Esc. Univ. Cienc. Salud ; 6(1): 36-46, ene.-jun. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1023753

RESUMO

Los anestésicos locales han cambiado de manera destacada la historia y la práctica de la medicina, la evolución en los métodos de desarrollo de anestésicos ha hecho posible el desarrollo de anestésicos convencionales para uso común en procedimientos médicos quirúrgicos locales, hablando en especial de dos anestésicos que se utilizan diariamente en los diferentes niveles de atención de salud mundial, la lidocaína y posteriormente la lidocaína con epinefrina. Es por el uso cotidiano de estos anestésicos que ahora es posible hacer procedimientos menores en los pacientes sin exponer a los mismos al dolor de los procedimientos propiamente dicho o la causa de dolor no procedimental. Se utiliza cada uno de acuerdo al efecto deseado que se requiera en el paciente, teniendo en cuenta las diversas precaucio-nes dada la potencial toxicidad que poseen, así como la técnica que se va a utilizar. En este artículo de revisión bibliográfica, se presentan las generalidades de ambos anestésicos, las indicaciones, precauciones, efectos adversos y comparación de toxici-dad entre ambos anestésicos. Esta revisión bibliográfica se realizó a partir de 36 artícu-los tomando como referencia los siguientes: literatura médica, artículos de revistas cien-tíficas y otras revisiones bibliográficas menores de 5 años de haber sido publica-dos o aquellos con relevancia histórica...(AU)


Assuntos
Humanos , Epinefrina/farmacologia , Anestésicos Locais , Lidocaína/farmacocinética , Revisão
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