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1.
J Agric Food Chem ; 70(16): 4899-4911, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35437986

RESUMO

Bacterial biofilms are the root cause of persistent and chronic phytopathogenic bacterial infections. Therefore, developing novel agrochemicals that target the biofilm of phytopathogenic bacteria has been regarded as an innovative tactic to suppress their invasive infection or decrease bacterial drug resistance. In this study, a series of natural pterostilbene (PTE) derivatives were designed, and their antibacterial potency and antibiofilm ability were assessed. Notably, compound C1 displayed excellent antibacterial potency in vitro, affording an EC50 value of 0.88 µg mL-1 against Xoo (Xanthomonas oryzae pv. oryzae). C1 could significantly reduce biofilm formation and extracellular polysaccharides (EPS). Furthermore, C1 also possessed remarkable inhibitory activity against bacterial extracellular enzymes, pathogenicity, and other virulence factors. Subsequently, pathogenicity experiments were further conducted to verify the above primary outcomes. More importantly, C1 with pesticide additives displayed excellent control efficiency. Given these promising profiles, these pterostilbene derivatives can serve as novel antibiofilm agents to suppress plant pathogenic bacteria.


Assuntos
Infecções Bacterianas , Oryza , Xanthomonas , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana , Oryza/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Propanolaminas , Estilbenos
2.
Medicine (Baltimore) ; 101(13): e29124, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35421065

RESUMO

BACKGROUND: In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks. METHODS: A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered. RESULTS: The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment. CONCLUSION: Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock. ETHICS AND DISSEMINATION: Ethical permissions are not required as prepublished data are used. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/SKEZ7.


Assuntos
Choque Séptico , Humanos , Metanálise como Assunto , Propanolaminas , Projetos de Pesquisa , Choque Séptico/tratamento farmacológico , Revisões Sistemáticas como Assunto , Resultado do Tratamento
3.
Med Klin Intensivmed Notfmed ; 117(3): 200-205, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-35298671

RESUMO

Heart rate is well established in the diagnosis of shock; however, the mechanisms regulating heart rate, systemic resistance and blood pressure remain unclear. The concept of heart rate control in shock-related tachycardia has been known for about 50 years. Elevated heart rates in septic shock have been identified as an indicator of increasingly inefficient hemodynamics, worsening perfusion and organ function as well as of an unfavourable prognosis. Many drugs used for heart rate control also lower blood pressure. The challenge of this therapeutic concept is achieving optimal heart rate control without provoking critical hypotension. Only in recent years has the development of highly cardioselective, short- and ultrashort-acting ß­blockers such as esmolol and landiolol made it possible to prove the feasibility and usefulness of heart rate control in certain types of shock.


Assuntos
Propanolaminas , Choque Séptico , Antagonistas Adrenérgicos beta/uso terapêutico , Frequência Cardíaca , Hemodinâmica , Humanos , Propanolaminas/uso terapêutico , Choque Séptico/tratamento farmacológico , Taquicardia/tratamento farmacológico , Taquicardia/etiologia
4.
J Int Med Res ; 50(3): 3000605221078705, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35277087

RESUMO

OBJECTIVE: To determine the intravenous (i.v.) dose of esmolol needed to attenuate blood loss in patients undergoing posterior lumbar internal fixation (PLIF) surgery. METHODS: This study randomized patients to either the E5 or E10 group. Patients in the E5 group received a 0.25 mg/kg i.v. loading dose of esmolol before anaesthesia, followed by an infusion of 5 µg/kg/min throughout the operation. Patients in the E10 group received a 0.5 mg/kg i.v. loading dose of esmolol before anaesthesia, followed by an infusion of 10 µg/kg/min throughout the operation. RESULTS: The study analysed 33 patients: 16 in the E5 group and 17 in the E10 group. The mean ± SD blood loss at the end of surgery was significantly greater in the E5 than E10 group (586.3 ± 160.1 versus 347.7 ± 138.0 ml, respectively). The total amount of patient-controlled analgesia (PCA) used was significantly higher in the E5 than E10 group at 8 (26.1 ± 12.0 versus 17.5 ± 8.3 ml, respectively), 24 (58.4 ± 21.3 versus 44.1 ± 16.2 ml, respectively) and 48 h after surgery (90.0 ± 22.5 versus 69.3 ± 22.1 ml, respectively). CONCLUSION: A continuous infusion of 10 µg/kg/min of esmolol can safely reduce blood loss during PLIF surgery. It was also shown to reduce postoperative PCA consumption.


Assuntos
Dor Pós-Operatória , Propanolaminas , Analgesia Controlada pelo Paciente , Humanos , Dor Pós-Operatória/tratamento farmacológico , Propanolaminas/uso terapêutico , Estudos Prospectivos
5.
J Healthc Eng ; 2022: 7363589, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35256901

RESUMO

Objective: To investigate a rapid and effective method for the examination of coronary CTA in emergency patients requiring coronary CTA examination, who have faster heart rate (≧80 bpm) or cannot cooperate with the examination due to the inability of breath holding at poor physical conditions. Methods: Before coronary CTA examination, with the ECG monitoring, intravenous injection of esmolol was given to achieve rapid heart rate reduction. Without the patient's cooperation, coronary CTA examination was then performed in a quick and effective manner using the 640-slice high-speed CT. The diagnosis report was obtained through the subsequent reconstruction analysis using artificial intelligence software. Conclusion: Esmolol injection can rapidly reduce the heart rate of normal people during exercise and at rest, and the steady blood concentration can be reached in 2 minutes. The half-life is about 5 minutes, with short duration and fewer side effects on patients. The diagnostic rate of coronary artery segment using (excellent + good) CTA image of the patients with esmolol and artificial intelligence analysis in the experimental group was 95.4%, while the diagnostic rate was 91.1% in the control group, and there was no significant statistical difference between the two groups (P > 0.05). Esmolol injection can rapidly reduce heart rate in patients with high heart rate, without holding breath or long-term preoperative preparation; the combination with the analysis of subsequent artificial intelligence reconstruction is a new method for rapid and effective coronary CTA examination in all patients.


Assuntos
Inteligência Artificial , Propanolaminas , Angiografia Coronária/métodos , Frequência Cardíaca/fisiologia , Humanos , Propanolaminas/uso terapêutico
6.
Am J Mens Health ; 16(1): 15579883221075498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35135369

RESUMO

The elder population has increased, introducing the profound medical and social challenge of maintaining health in aging seniors and the need for a medical approach to sustaining physical and mental health. The relationship between diseases and lifestyle-related factors such as diet and exercise are important. A health-conscious lifestyle improves one's health condition from a medical perspective, as indicated by new wellness monitoring using health devices and recent research into the efficacy of functional lunches incorporating utilitarian agricultural, forestry, and fishery products and foods. For a period of 3 months, and solely at lunchtime, 21 participants consumed the contents of a bento (Japanese box lunch), which incorporated functional (healthy) foods. A variety of factors were analyzed, including: weight, weight fluctuation rate, abdominal girth, triglycerides, total cholesterol value, and 8-OHdG (8-hydroxy-2'-deoxyguanosine). The bento comprising functional foods resulted in a reduction in both weight and abdominal girth without calorie restrictions. A reduction over time was observed in 8-OHdG, an oxidative stress marker, as compared to values prior to initiation of the study. Usage of a health device, exercise/dietary advice from a physician and nutritionist, and the availability of meals incorporating functional agricultural products might help prevent lifestyle disease and lead to improved health management.


Assuntos
Alimento Funcional , Almoço , Idoso , Dieta , Humanos , Japão , Masculino , Estresse Oxidativo , Projetos Piloto , Propanolaminas
7.
Int J Mol Sci ; 23(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35163250

RESUMO

Von Hippel-Lindau (VHL) syndrome is a rare inherited cancer disease where the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HBs), CNS-HBs, and clear cell renal cell carcinoma (ccRCC). Since standard therapies in VHL have shown limited response, leaving surgery as the only possible treatment, targeting of the ß2-adrenergic receptor (ADRB2) has shown therapeutic antitumor benefits on VHL-retinal HBs (clinical trial), VHL-CNS HBs, and VHL-ccRCC (in vitro and in vivo). In the present study, we wanted to look deep into the effects of the ADRB2 blockers propranolol and ICI-118,551 on two main aspects of cancer progression: (i) the changes on the inflammatory response of ccRCC cells; and (ii) the modulation on the Warburg effect (glycolytic metabolism), concretely, on the expression of genes involved in the cell reactive oxygen species (ROS) balance and levels. Accordingly, in vitro studies with primary VHL-ccRCC and 786-O cells measuring ROS levels, ROS-expression of detoxifying enzymes, and the expression of p65/NF-κB targets by RT-PCR were carried out. Furthermore, histological analyses of ccRCC samples from heterotopic mouse xenografts were performed. The obtained results show that ADRB2 blockade in ccRCC cells reduces the level of oxidative stress and stabilizes the inflammatory response. Thus, these data further support the idea of targeting ADRB2 as a promising strategy for the treatment of VHL and other non-VHL tumors.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Inflamação/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores Adrenérgicos beta 2/metabolismo , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hemangioblastoma/tratamento farmacológico , Hemangioblastoma/metabolismo , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Propanolaminas/farmacologia , Propranolol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Doença de von Hippel-Lindau/tratamento farmacológico , Doença de von Hippel-Lindau/metabolismo
8.
Shock ; 57(4): 508-517, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35066509

RESUMO

INTRODUCTION: Septic shock is often characterized by tachycardia and a hyperdynamic hemodynamic profile. Use of the beta antagonist esmolol has been proposed as a therapy to lower heart rate, thereby improving diastolic filling time and improving cardiac output, resulting in a reduction in vasopressor support. METHODS: We conducted a two-center, open-label, randomized, Phase II trial comparing esmolol to placebo in septic shock patients with tachycardia. The primary endpoint was improvement in hemodynamics as measured by the difference in norepinephrine equivalent dose (NED) between groups at 6 hours after initiation of study drug. Secondary outcomes included assessing differences in inflammatory biomarkers and oxygen consumption (VO2). RESULTS: A total of 1,122 patients were assessed for eligibility and met inclusion criteria; 42 underwent randomization, and 40 received study interventions (18 in the esmolol arm and 22 in the usual care arm). The mean NED at 6 h was 0.30 ±â€Š0.17 mcg/kg/min in the esmolol arm compared to 0.21 ±â€Š0.19 in the standard care arm (P = 0.15). There was no difference in number of shock free days between the esmolol (2, IQR 0, 5) and control groups (2.5, IQR 0, 6) (P = 0.32). There were lower levels of C-reactive protein at 12 and 24 h in the esmolol arm, as well as a statistically significant difference in trend over time between groups. There were no differences in terms of IL-4, IL-6, IL-10, and TNFα. Among a subset who underwent VO2 monitoring, there was decreased oxygen consumption in the esmolol patients; the mean difference between groups at 24 h was -2.07 mL/kg/min (95% CI -3.82, -0.31) (P = 0.02), with a significant difference for the trend over time (P < 0.01). CONCLUSION: Among patients with septic shock, infusion of esmolol did not improve vasopressor requirements or time to shock reversal. Esmolol was associated with decreased levels of C-reactive protein over 24 h. TRIAL REGISTRATION: www.clinicaltrials.gov. Registered February 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02369900.


Assuntos
Propanolaminas , Choque Séptico , Proteína C-Reativa , Hemodinâmica , Humanos , Norepinefrina/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Choque Séptico/tratamento farmacológico , Taquicardia , Vasoconstritores/uso terapêutico
9.
Br J Ophthalmol ; 106(3): 403-408, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33214244

RESUMO

BACKGROUND/AIMS: Stargardt disease is a rare, inherited, degenerative disease of the retina that is the most common type of hereditary macular dystrophy. Currently, no approved treatments for the disease exist. The purpose of this study was to characterise the pharmacodynamics of emixustat, an orally available small molecule that targets the retinal pigment epithelium-specific 65 kDa protein (RPE65), in subjects with macular atrophy secondary to Stargardt disease. METHODS: In this multicentre study conducted at six study sites in the USA, 23 subjects with macular atrophy secondary to Stargardt disease were randomised to one of three doses of daily emixustat (2.5 mg, 5 mg or 10 mg) and treated for 1 month. The primary outcome was the suppression of the rod b-wave recovery rate on electroretinography after photobleaching, which is an indirect measure of RPE65 inhibition. RESULTS: Subjects who received 10 mg emixustat showed near-complete suppression of the rod b-wave amplitude recovery rate postphotobleaching (mean=91.86%, median=96.69%), whereas those who received 5 mg showed moderate suppression (mean=52.2%, median=68.0%). No effect was observed for subjects who received 2.5 mg emixustat (mean=-3.31%, median=-12.23%). The adverse event profile was consistent with prior studies in other patient populations and consisted primarily of ocular adverse events likely related to RPE65 inhibition. CONCLUSION: This study demonstrated dose-dependent suppression of rod b-wave amplitude recovery postphotobleaching, confirming emixustat's biological activity in patients with Stargardt disease. These findings informed dose selection for a 24-month phase 3 trial (SeaSTAR Study) that is now comparing emixustat to placebo in the treatment of Stargardt disease-associated macular atrophy.


Assuntos
Degeneração Macular , Éteres Fenílicos , Atrofia , Eletrorretinografia , Humanos , Degeneração Macular/complicações , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Éteres Fenílicos/efeitos adversos , Propanolaminas , Doença de Stargardt
10.
Braz J Anesthesiol ; 72(1): 95-102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34582903

RESUMO

INTRODUCTION AND OBJECTIVES: Although lidocaine is widely used to prevent cardiovascular changes resulting from laryngoscopy and orotracheal intubation, it is still unclear whether there are more efficacious drugs. This study aimed to compare the beta-blocker esmolol with lidocaine regarding the effects on hemodynamic response after orotracheal intubation. METHODS: The study has a prospective, randomized, double-blind, superiority design, and assessed 69 participants between 18 and 70 years of age, ASA I-II, scheduled for elective or emergency surgery under general anesthesia with orotracheal intubation. Participants were randomly allocated to receive 1.5 mg.kg-1 esmolol bolus followed by 0.1 mg.kg-1.min-1 esmolol infusion (n = 34) or 1.5 mg.kg-1 lidocaine bolus followed by 1.5 mg.kg-1.h-1 lidocaine infusion (n = 35). We recorded changes in heart rate, arterial blood pressure and incidence of adverse events. RESULTS: Post-intubation tachycardia episodes were significantly less frequent in the esmolol group (5.9% vs. 34.3%; Relative Risk (RR) 0.17; 95% Confidence Interval (95% CI) 0.04-0.71; Number Needed to Treat (NNT) 3.5; p = 0.015. After orotracheal intubation, mean heart rate was significantly lower in the esmolol group (74.5 vs. 84.5, p = 0.006). Similar results were observed in the subsequent 3 and 6 minutes (75.9 vs. 83.9, p = 0.023 and 74.6 vs. 83.0, p = 0.013, respectively). CONCLUSION: Esmolol was a safe and more effective intervention to reduce incidence of tachycardia and control heart rate immediately after tracheal intubation when compared to lidocaine.


Assuntos
Lidocaína , Propanolaminas , Pressão Sanguínea , Método Duplo-Cego , Frequência Cardíaca , Hemodinâmica , Humanos , Intubação Intratraqueal/efeitos adversos , Laringoscopia/efeitos adversos , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Estudos Prospectivos , Taquicardia/tratamento farmacológico , Taquicardia/etiologia , Taquicardia/prevenção & controle
11.
Pharmacology ; 107(1-2): 116-121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34781292

RESUMO

Fenoterol is a ß2-adrenoceptor (AR)-selective agonist that is commonly used to investigate relaxation responses mediated by ß2-AR in smooth muscle preparations. Some data have questioned this because fenoterol had low potency in the rat urinary bladder when a muscarinic agonist was used as a pre-contraction agent and because some investigators proposed that fenoterol may act in part via ß3-AR. We designed the present study to investigate whether fenoterol is a proper pharmacological tool to study ß2-AR-mediated relaxation responses in the rat urinary bladder. Firstly, we have compared the effect of pre-contraction agents on fenoterol potency and found that fenoterol potency was about 1.5 log units greater against KCl than carbachol (pEC50 7.19 ± 0.66 and 5.62 ± 1.09 of KCl and of carbachol, respectively). To test the selectivity of fenoterol, we have determined the effects of the ß2-AR antagonist ICI 118,551 and the ß3-AR antagonist L 748,337 on relaxation responses to fenoterol. While 300 nM L 748,337 had little effect on the potency of fenoterol (pEC50 6.56 ± 0.25 and 6.33 ± 0.61 in the absence and presence of L 748,337, respectively), the relaxation curve for fenoterol was right-shifted in the presence 300 nM ICI 118,551 (pEC50 5.03 ± 0.18). Thus, we conclude that fenoterol is a proper pharmacological tool to assess ß2-AR-mediated responses in the rat urinary bladder and most likely in other smooth-muscle preparations containing multiple subtypes of the ß-AR.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Fenoterol/farmacologia , Bexiga Urinária/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Aminofenóis/farmacologia , Aminofenóis/uso terapêutico , Animais , Carbacol/farmacologia , Carbacol/uso terapêutico , Feminino , Fenoterol/uso terapêutico , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Cloreto de Potássio/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Ratos Sprague-Dawley , Ratos Wistar , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
12.
Clin Pharmacol Drug Dev ; 11(3): 309-317, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34655181

RESUMO

We investigated the hemodynamic effects of 2 short-acting ß1 -blockers, landiolol and esmolol, in the continuous presence of dobutamine in a prospective, single-center, randomized, crossover study in 16 healthy White volunteers. Dobutamine was infused at a rate sufficient to increase the heart rate by at least 30 beats per minute, followed by a 60-minute infusion of 50 µg/kg/min esmolol or 10 µg/kg/min landiolol on top of the unchanged dobutamine infusion. Concentrations of ß-blockers and their metabolites in blood, heart rate, and blood pressure were followed for 180 minutes. Landiolol reduced the dobutamine-induced heart rate and blood pressure increases better than esmolol. After discontinuation of ß-blocker administration, heart rate recovered swiftly to preinfusion values in both study arms. Systolic and diastolic blood pressure recovered partially after landiolol but showed a continued reduction after esmolol. No serious adverse events were observed. The heart rate effect is characteristic for ß-blockers, whereas the blood pressure effects are likely due to direct and indirect ß-blocker effects as well as influences on various ion channels. This may explain why landiolol that is devoid of effects on renin and sodium, calcium, and potassium channels behaves different from esmolol with respect to blood pressure recovery.


Assuntos
Dobutamina , Pressão Sanguínea , Estudos Cross-Over , Dobutamina/farmacologia , Humanos , Morfolinas , Propanolaminas , Estudos Prospectivos , Ureia/análogos & derivados
13.
Can Assoc Radiol J ; 73(1): 240-248, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34293933

RESUMO

BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Hemodinâmica/efeitos dos fármacos , Metoprolol/administração & dosagem , Propanolaminas/administração & dosagem , Administração Intravenosa , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/economia , Angiografia por Tomografia Computadorizada/economia , Angiografia Coronária/economia , Análise Custo-Benefício/economia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Metoprolol/economia , Pessoa de Meia-Idade , Propanolaminas/economia , Estudos Prospectivos , Método Simples-Cego
14.
Ann Surg Oncol ; 29(3): 1695-1702, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34709494

RESUMO

BACKGROUND: Pregnancy-associated breast cancer (PABC) and concurrent, or early development of, stage IV disease is uncommon. Given this rarity, and complexities surrounding pregnancy, data are limited regarding PABC treatment and outcomes. We evaluated oncologic, obstetric, and fetal outcomes of women with stage IV PABC in relation to presentation timing and treatment. PATIENTS AND METHODS: Our retrospective review of an institutional database identified women with stage IV PABC from 1998 to 2018. PABC was defined as diagnosis during pregnancy or ≤ 1 year postpartum. Clinicopathologic, treatment, and outcome variables were compared between women diagnosed during pregnancy versus postpartum. RESULTS: We identified 77 women (median age 35 years; interquartile range [IQR] 32-37 years): 51 (66%) in the postpartum group and 26 (34%) in the pregnant group, including 9 with therapeutic or spontaneous abortion. Among 17 women who continued pregnancy, no obstetric or fetal complications were noted. Clinicopathologic and treatment variables did not differ between groups. Of 43 women dead from disease, 15 had triple negative (TN) tumors. Median overall survival (OS) of TN tumors was 14 months (range 5-39 months); OS was associated with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2) positive tumors (p < 0.01). At 31 months (range 0-137 months) median follow-up, the 5-year OS was 34% (95% confidence interval 21-46%), and did not differ among pregnant and postpartum groups (p = 0.2). CONCLUSIONS: Women with stage IV TN PABC had high mortality rates despite multimodality therapy. Timing of presentation did not affect management decisions or OS, even for women who completed pregnancy. Further research to understand PABC biology, focusing on TN tumors, is warranted.


Assuntos
Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Neoplasias de Mama Triplo Negativas , Adulto , Azidas , Neoplasias da Mama/terapia , Feminino , Humanos , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/terapia , Propanolaminas , Estudos Retrospectivos
15.
Curr Rev Clin Exp Pharmacol ; 17(2): 85-89, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34719377

RESUMO

BACKGROUND: The current recommendations of the American College of Cardiology/ American Heart Association and a previous Bayesian analysis clearly show a mortality benefit with the use of ß- blockers in chronic HF, especially for bisoprolol, carvedilol, and sustained-release metoprolol succinate. OBJECTIVE: The main objective was to report the evidence on the use of the afore-mentioned ß-blockers in subjects with heart failure and to characterize the stages of heart failure in response to the four different ß-blockers. Furthermore, it shed light on the patient's satisfaction and improved quality of life using the afore-mentioned ß-blockers in subjects with heart failure. METHODS: The current perspective presented the clinical outcomes, including hospitalization, morbidity, mortality, patient's satisfaction, and quality of life, of four beta (ß)-blockers, namely bisoprolol, carvedilol, metoprolol succinate, and nebivolol in different stages of heart failure. RESULTS: The use of these three agents should be recommended for all stable subjects with current or previous symptoms of heart failure and heart failure with reduced ejection fraction unless there is any contraindication. The fore-mentioned ß-blockers (bisoprolol, carvedilol, and metoprolol succinate) can be initiated early, even in stable and symptom-free (at rest) subjects with heart failure. ß-blockers in heart failure should be commenced at small doses and then titrated upward as tolerated to achieve the desired clinical effects on heart rate and symptom control. CONCLUSION: Cardiologists should weigh the benefit-risk in subjects with heart failure and other coexisting cardiovascular problems such as atrial fibrillation and diabetes.


Assuntos
Insuficiência Cardíaca , Propanolaminas , Teorema de Bayes , Carbazóis/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Qualidade de Vida , Resultado do Tratamento , Estados Unidos
16.
J Vet Emerg Crit Care (San Antonio) ; 32(2): 243-248, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34874604

RESUMO

OBJECTIVE: To describe the indications and clinical response for dogs and cats treated with esmolol. DESIGN: Retrospective case series from 2003 to 2020. SETTING: Single university veterinary teaching hospital. ANIMALS: Twenty-two dogs and 6 cats. INTERVENTIONS: Animals received either a bolus or bolus and continuous rate infusion of the ultrashort-acting beta receptor antagonist, esmolol. MEASUREMENTS AND MAIN RESULTS: Twenty-two animals were treated for either a supraventricular or sinus tachycardia, 5 were treated for a ventricular tachycardia, and 1 was treated for atrial fibrillation. Esmolol was most frequently used in dogs (N = 9) who had ingested a toxin such as albuterol, amphetamine, or chocolate. Esmolol was administered at median bolus dose of 330 µg/kg (range 10-1000 µg/kg) and continued as a continuous rate infusion in 15 animals at a median dose of 50 µg/kg/min. Defining success as a reduction in heart rate of 20% or greater, esmolol therapy was considered successful in 13 of 28 animals (46%). Animals treated for a toxicosis were more likely to have a successful rate reduction than those treated for other causes (P = 0.006). Nineteen animals survived to discharge. Both treatment success (P = 0.046) and treatment for a toxicosis (P = 0.003) were associated with survival. CONCLUSIONS: Esmolol administration was well tolerated by dogs and cats with tachycardia due to intoxication. Heart rate reduction by at least 20% was achieved in 46% of cases. Animals with toxin ingestion were more likely to be discharged from the hospital.


Assuntos
Doenças do Gato , Doenças do Cão , Propanolaminas , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Doenças do Gato/induzido quimicamente , Doenças do Gato/tratamento farmacológico , Gatos , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Cães , Frequência Cardíaca , Hospitais Veterinários , Hospitais de Ensino , Propanolaminas/uso terapêutico , Estudos Retrospectivos , Taquicardia/tratamento farmacológico , Taquicardia/veterinária
17.
Nitric Oxide ; 119: 19-28, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902580

RESUMO

In this study, we investigated the possible role of the l-cysteine/hydrogen sulfide pathway in ß3-adrenoceptors-mediated relaxation in isolated mouse gastric fundus tissue. l-cysteine (endogenous H2S; 10-6-10-2 M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10-6-10-3 M), selective ß3-adrenoceptors agonist BRL 37344 (10-9-10-4 M) and non-selective ß-adrenoceptor agonist isoprenaline (10-9-10-4 M) produced concentration-dependent relaxation in mouse gastric fundus. The non-selective ß-adrenoceptors antagonist propranolol (10-6 M) inhibited the relaxant response to isoprenaline but not to BRL 37344. On the other hand, the selective ß3-adrenoceptors antagonist SR 59230A (10-5 M) inhibited the relaxant responses to BRL 37344. In addition, cystathionine-gamma-lyase (CSE) inhibitor D,L-propargylglycine (PAG, 10-2 M), cystathionine-beta-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10-2 M), and the combination of these inhibitors significantly reduced the relaxant responses induced by l-cysteine and BRL 37344. Pre-incubation of gastric fundal strips with propranolol (10-6 M) and SR 59230A (10-5 M) did not affect relaxations to l-cysteine and NaHS. Also, the existence of CSE, CBS, 3-mercaptopurivate sulfur transferase (3-MST) enzymes and ß3-adrenoceptors were detected in gastric fundal tissue. Furthermore, basal H2S release was detected in the measurements. H2S level increased in the presence of l-cysteine, NaHS, and BRL 37344. The increase in H2S level by l-cysteine and BRL 37344 decreased significantly with PAG and AOAA enzyme inhibitors. These results suggest that endogenous H2S is synthesized from l-cysteine at least by CBS and CSE enzymes. Also, ß3-adrenoceptors are found in the mouse stomach fundus and mediate BRL 37344-induced relaxations, and l-cysteine/hydrogen sulfide pathway plays a partial role in ß3-adrenoceptors-mediated relaxation in mouse gastric fundus tissue.


Assuntos
Cisteína/metabolismo , Fundo Gástrico/metabolismo , Sulfeto de Hidrogênio/metabolismo , Relaxamento Muscular/fisiologia , Receptores Adrenérgicos beta 3/metabolismo , Animais , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Etanolaminas/farmacologia , Fundo Gástrico/enzimologia , Isoproterenol/farmacologia , Masculino , Camundongos , Propanolaminas/farmacologia , Propranolol/farmacologia , Sulfurtransferases/metabolismo
18.
Shanghai Kou Qiang Yi Xue ; 30(5): 548-550, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34888612

RESUMO

PURPOSE: To compare the effect of dexmedetomidine (Dex) and esmolol on controlled hypotension in patients with orthognathic surgery. METHODS: From January 2017 to December 2019, a total of 109 patients were treated with Dex (group D) and esmolol (group E) during orthognathic surgery (Le Fort I osteotomy of maxilla and sagittal split of mandibular ramus) in our hospital. Heart rate(HR) and mean arterial pressure(MAP) during controlled hypotension (the difference between the highest and lowest values and the percentage of basic values), intraoperative blood loss, allogeneic blood transfusion, operation time and dosage of propofol and remifentanil were compared between the two groups. The data were statistically analyzed using SPSS 22.0 software package. RESULTS: Compared with group E, HR and MAP, dose of propofol and remifentanil in group D were significantly lower than those in group E (P<0.05). There was no significant difference among other indexes. CONCLUSIONS: Compared with esmolol, the effect of Dex on controlled hypotension during orthognathic surgery is more stable and the dosage of propofol and remifentanil is decreased.


Assuntos
Dexmedetomidina , Hipotensão Controlada , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Dexmedetomidina/uso terapêutico , Humanos , Propanolaminas
19.
Drug Des Devel Ther ; 15: 5025-5033, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934307

RESUMO

PURPOSE: The aim of this study was to investigate the efficacy of esmolol on intraoperative hemodynamic and perioperative analgesic management. METHODS: Totally, 125 patients undergoing colectomy were randomly divided into three groups. Group S (saline group) was administered 0.75 mL/kg/h of normal saline for 5 min before anesthesia induction and maintenance of 0.25 mL/kg/h; Group E1 and Group E2 were administered 0.5 mg/kg and 1.0 mg/kg esmolol for 5 min before anesthesia induction, and maintained of 0.5 mg/kg/h and 2.0 mg/kg/h, respectively. Several parameters including indexes of hemodynamics variation (primary outcome), intra- and postoperative analgesic usage, and pain score were measured. RESULTS: Group E1 and Group E2 had significantly lower intubation response than Group S (P = 0.007, P = 0.001), and extubation response of Group E2 was significantly lower than Group S (P = 0.007). The opioid consumption in Group E1 and Group E2 was significantly lower than in Group S intraoperatively (P = 0.020 and 0.007). The incidence of postoperative adverse reactions among the three groups was not statistically significant (P = 0.368 and 0.772). CONCLUSION: Esmolol 0.5 mg/kg and 1.0 mg/kg infusion before intubation both can effectively inhibit the intubation response, while only maintenance with 2.0 mg/kg/h of esmolol can reduce the incidence of extubation response. At the same time, esmolol can decrease intraoperative opioid requirement without increasing the risk of adverse reactions. TRIAL REGISTRATION: ChiCTR1900024538 and the date of registration was July 15, 2019 at http://www.chictr.org.cn.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Colectomia , Hemodinâmica/efeitos dos fármacos , Dor Pós-Operatória/tratamento farmacológico , Propanolaminas/administração & dosagem , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos
20.
Int J Mol Sci ; 22(22)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34830051

RESUMO

Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not yet fully understood; however, it is usually assumed to be a pathological process that augments epileptic activity. Using whole-cell patch-clamp recordings in rat entorhinal cortex slices, we demonstrate that the timing of epileptiform discharges, induced by 4-aminopyridine and gabazine, is determined by the shunting effect of Ca2+-dependent slow conductance, mediated predominantly by K+-channels. The blockade of CP-AMPARs by IEM-1460 eliminates this extra conductance and consequently increases the rate of discharge generation. The blockade of NMDARs reduced the additional conductance to a lesser extent than the blockade of CP-AMPARs, indicating that CP-AMPARs are a more significant source of intracellular Ca2+. The study's main findings were implemented in a mathematical model, which reproduces the shunting effect of activity-dependent conductance on the generation of discharges. The obtained results suggest that the expression of CP-AMPARs in principal neurons reduces the discharge generation rate and may be considered as a protective mechanism.


Assuntos
Córtex Entorrinal/metabolismo , Epilepsia/metabolismo , Neurônios/metabolismo , Receptores de AMPA/metabolismo , Adamantano/análogos & derivados , Adamantano/farmacologia , Animais , Cálcio/metabolismo , Simulação por Computador , Maleato de Dizocilpina/farmacologia , Epilepsia/induzido quimicamente , Antagonistas de Receptores de GABA-B/farmacologia , Técnicas In Vitro , Masculino , Membranas/efeitos dos fármacos , Modelos Teóricos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ácidos Fosfínicos/farmacologia , Propanolaminas/farmacologia , Ratos Wistar , Receptores de AMPA/antagonistas & inibidores , Receptores de GABA-B/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
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