Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33.976
Filtrar
2.
Artigo em Inglês | MEDLINE | ID: mdl-38973817

RESUMO

Background: The positive predictive value (PPV) of the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) code for "essential and other specified forms of tremor" in identifying essential tremor (ET) cases was found to be less than 50%. The ability of the ICD-10-CM G25.0 code for "essential tremor" to identify ET has not been determined. The study objective was to determine the PPV of the G25.0 code. Methods: Patients in a tertiary health system with a primary care encounter associated with ICD-10-CM code G25.0 in 2022 underwent medical record review to determine if the consensus criteria from the International Parkinson and Movement Disorder Society for an ET diagnosis were met. Results: 442 patients were included. The PPV of G25.0 in identifying probable ET cases was 74.7% (95% confidence interval (CI) 70.4-78.5%). Among patients prescribed propranolol, the PPV improved to 87.8% (95% CI 78.0-93.6%). Discussion: Compared to the ICD-9-CM code 333.1, G25.0 is superior for identifying ET cases. A potential limitation of this study is that the consensus criteria applied relies on nonspecific physical exam findings which may lead to an overestimation of the PPV of G25.0. Highlights: The ICD-10-CM diagnosis code for essential tremor has not been previously validated. The objective of this study was to determine the PPV of the G25.0 code. The PPV in identifying essential tremor cases was 74.7%. The PPV improved among patients prescribed propranolol.


Assuntos
Tremor Essencial , Classificação Internacional de Doenças , Humanos , Tremor Essencial/diagnóstico , Tremor Essencial/classificação , Classificação Internacional de Doenças/normas , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Propranolol/uso terapêutico
3.
Medicine (Baltimore) ; 103(28): e38839, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996090

RESUMO

Left ventricular assist devices (LVADs) are widely used as end-stage therapy in patients with advanced heart failure, whereas implantation increases the risks of development of sustained ventricular tachycardia at the later postimplantation stage. Therefore, this study aimed to evaluate the clinical efficacy of orally administered amiodarone and propranolol in 3 patients with ventricular tachycardia (VT) after LVAD implantation who were resistant to initial anti-antiarrhythmic drugs. This retrospective cohort study consisted of the initial evaluation of the clinical data of 14 adult patients who underwent implantation of LVAD between January 2019 and March 2021. A total of 3 patients with resistant VT were finally included. In all cases, the patients were initially administered amiodarone in the different doses intravenously to stabilize the critical condition, whereas its oral form along with that of propranolol was used as maintenance therapy in the first 2 cases. In the third case, amiodarone was withdrawn because of the risk of development of hyperthyroidism, while oral propranolol was used in the treatment. The assessment in the 16-month follow-up period after discharge did not show presence of non-sustained and sustained VT in all 3 cases. In the ventricular arrhythmia-free group, the total mortality rate within the follow-up period was 11.1 ±â€…7.78 months in the 3 patients. We suggest that maintenance oral therapy of propranolol and amiodarone can significantly decrease the risks of complications in patients with VT after implantation of ventricular assist device in the long term.


Assuntos
Amiodarona , Antiarrítmicos , Propranolol , Taquicardia Ventricular , Humanos , Amiodarona/administração & dosagem , Amiodarona/efeitos adversos , Propranolol/administração & dosagem , Propranolol/uso terapêutico , Masculino , Antiarrítmicos/administração & dosagem , Estudos Retrospectivos , Administração Oral , Pessoa de Meia-Idade , Taquicardia Ventricular/tratamento farmacológico , Feminino , Adulto , Insuficiência Cardíaca/tratamento farmacológico , Idoso
4.
J Headache Pain ; 25(1): 119, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044170

RESUMO

OBJECTIVE: The aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis. METHODS: We report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared propranolol with placebo for migraine prophylaxis in adults. The outcomes of interest were informed by the Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in monthly migraine days, the reduction of monthly migraine days, and the number of adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB (risk of bias) 2.0 tool and the certainty of evidence by using the GRADE approach. RESULTS: Our search yielded twenty trials (n = 1291 patients) eligible for data synthesis and analysis. The analysis revealed a moderate certainty evidence that propranolol leads to a reduction in monthly migraine days versus placebo (-1.27; 95% CI: -2.25 to -0.3). We found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo with a relative risk of 1.65 (95% CI 1.41 to 1.93); absolute risk difference: 179 more per 1,000 (95% CI 113 to 256). We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30). CONCLUSIONS: The present meta-analysis shows that propranolol has a prophylactic role in migraine, with an overall acceptable tolerability profile. Combining these results with its long-standing use and its global availability at a low cost confirms its role as a first line agent in the prophylaxis of migraine.


Assuntos
Antagonistas Adrenérgicos beta , Transtornos de Enxaqueca , Propranolol , Propranolol/uso terapêutico , Propranolol/administração & dosagem , Humanos , Transtornos de Enxaqueca/prevenção & controle , Transtornos de Enxaqueca/tratamento farmacológico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Administração Oral , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Anal Chem ; 96(26): 10639-10647, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38889191

RESUMO

Hepatic toxicity is a leading cause of the termination of clinical trials and the withdrawal of therapeutics following regulatory approval. The detection of drug-induced liver injury (DILI) is therefore of importance to ensure patient safety and the effectiveness of novel small molecules and drugs. DILI encompasses drug-induced steatosis (DIS) and drug-induced phospholipidosis (DIPL) which involve the accumulation of excess intracellular lipids. Here, we develop hyperspectral stimulated Raman scattering (SRS) microscopy as a label-free methodology for discriminating DIS and DIPL in mammalian cell culture. We demonstrate that hyperspectral SRS imaging in tandem with spectral phasor analysis is capable of discriminating DIS and DIPL based on the nature and distribution of intracellular lipids resulting from each process. To demonstrate the practical application of this methodology, we develop a panel of alkyne-tagged propranolol analogues that display varying DILI effects. Using hyperspectral SRS imaging together with spectral phasor analysis, our label-free methodology corroborated the standard fluorescence-based assay for DILI. As a label-free screening method, it offers a convenient and expedient methodology for visualizing hepatotoxicity in cell cultures which could be integrated into the early stages of the drug development process for screening new chemical entities for DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Humanos , Microscopia Óptica não Linear/métodos , Análise Espectral Raman/métodos , Propranolol/química , Células Hep G2
6.
J Cardiovasc Pharmacol ; 84(1): 110-117, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38922579

RESUMO

ABSTRACT: Hypercatecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyperacute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n = 6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (left ventricle, P = 0.021; right ventricle, P = 0.021), with upregulation of reactive oxidative species and other profibrosis proteins, after catecholamine infusion alone. After 1 propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable with sham (left ventricle, P = 0.021; right ventricle, P = 0.043), with additional findings including downregulation of the apoptotic pathway and profibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 mitogen-activated protein kinase pathway and demonstrates profibrotic changes mediated by matrix metalloproteinase 9, alpha-smooth muscle actin, and fibroblast growth factor 23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 mitogen-activated protein kinase pathway, profibrosis, and extrinsic apoptosis pathway.


Assuntos
Antagonistas Adrenérgicos beta , Fibrose , Insuficiência Cardíaca , Norepinefrina , Propranolol , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Masculino , Propranolol/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Ratos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/induzido quimicamente , Norepinefrina/metabolismo , Epinefrina/toxicidade , Epinefrina/administração & dosagem , Fosforilação , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/enzimologia , Catecolaminas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
7.
Behav Pharmacol ; 35(5): 293-302, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38847463

RESUMO

Cancer patients often experience anticipatory nausea and vomiting (ANV) due to Pavlovian conditioning. Both N-methyl-D-aspartate and beta-adrenergic receptors are known to mediate memory formation, but their role in the development of ANV remains unclear. This study used a conditioned context aversion (CCA) paradigm, an animal model for ANV, to assess whether administration of the beta-adrenergic receptor antagonist propranolol or the N-methyl-D-aspartate receptor antagonist MK-801 immediately after CCA training has an effect on the later expression of CCA in CD1 male mice. In experiment 1, three groups were injected with lithium chloride (LiCl) to induce aversion in a novel context, resulting in CCA. A control group was injected with sodium chloride (NaCl). Following conditioning, two of the LiCl-treated groups received different doses of MK-801 (0.05 or 0.2 mg/kg), while the remaining LiCl-treated and NaCl-treated groups received a second NaCl injection. In experiment 2, two groups were injected with LiCl, and one group was injected with NaCl. After conditioning, one of the LiCl-treated groups received a propranolol injection (10 mg/kg). The remaining LiCl-treated and NaCl-treated groups received NaCl injections. Water consumption was measured in all groups 72 h later within the conditioning context. Postconditioning administration of propranolol, but not MK-801, attenuated CCA, as revealed by similar levels of water consumption in animals that received LiCl and propranolol relative to NaCl-treated animals. These findings suggest that beta-adrenergic receptor activation is crucial for the development of CCA. Therefore, propranolol may represent a novel therapeutic approach for cancer patients at high risk of ANV.


Assuntos
Antagonistas Adrenérgicos beta , Condicionamento Clássico , Modelos Animais de Doenças , Maleato de Dizocilpina , Propranolol , Propranolol/farmacologia , Animais , Maleato de Dizocilpina/farmacologia , Masculino , Camundongos , Antagonistas Adrenérgicos beta/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Náusea/tratamento farmacológico , Náusea/induzido quimicamente , Aprendizagem da Esquiva/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Vômito Precoce , Antagonistas de Aminoácidos Excitatórios/farmacologia , Relação Dose-Resposta a Droga
8.
Molecules ; 29(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38930938

RESUMO

Atenolol (ATE) and propranolol (PRO) inclusion complexes with ß-cyclodextrin have been investigated in aqueous solution. The aqueous solution was examined and characterized using UV-vis, fluorescence spectroscopy, and 1H NMR. The physical mixture was characterized using FTIR. The existence of inclusion complexes is confirmed by observing changes in spectroscopic properties. The ATE complex with ß-CD exhibited an interaction as host and (ß-CD) as a guest in a 1:1 ratio, with an inclusion constant K of 2.09 × 10-3 µM-1, as determined by the typical double-reciprocal graphs. Similarly, the PRO complex with ß-CD exhibited an interaction as host and (ß-CD) guest in 1:1 and 1:2 stoichiometry at the same time; the inclusion constants were K1 = 5.80 × 10-5 µM-1 and K2 = 4.67 × 10-8 µM-1, as determined by typical double-reciprocal graphs. The variables influencing the formation of the inclusion complexes were investigated and optimized. Based on the enhancement in fluorescence intensity due to the formation of inclusion complexes, spectrofluorometric methods were developed and validated for determination of each drug's pharmaceutical formulation. The quantification of the fluorescence intensity for ATE and PRO was conducted at λex/λem 226/302 nm and λex/λem 231/338 nm, respectively. Under the optimal reaction circumstances, linear relationships with good correlation coefficients of 0.9918 and 0.99 were found in the concentration ranges of 0.3-1.7 µM, and 0.1-1.1 µM for ATE and PRO, respectively. The limits of detection (LODs) were found to be 0.13 and 0.01 µM for ATE and PRO, respectively. The suggested approach was effectively applied to the analysis of both drugs' pharmaceutical formulations.


Assuntos
Atenolol , Propranolol , Espectrometria de Fluorescência , beta-Ciclodextrinas , Atenolol/química , beta-Ciclodextrinas/química , Propranolol/química , Espectrometria de Fluorescência/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Ressonância Magnética/métodos
9.
Sci Rep ; 14(1): 14029, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890353

RESUMO

Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (ß-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.


Assuntos
Consumo Excessivo de Bebidas Alcoólicas , Modelos Animais de Doenças , Ratos Wistar , Animais , Feminino , Consumo Excessivo de Bebidas Alcoólicas/tratamento farmacológico , Masculino , Ratos , Etanol , Antagonistas Adrenérgicos/farmacologia , Naltrexona/farmacologia , Propranolol/farmacologia , Fatores Sexuais , Consumo de Bebidas Alcoólicas
10.
J Neuroimmune Pharmacol ; 19(1): 33, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900343

RESUMO

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary injury. Administration of propranolol for TBI maydecrease mortality and improve functional outcomes. However, it is our sense that its use has not been universally adopted due to low certainty evidence. The literature was reviewed to explore the mechanism of propranolol as a therapeutic intervention in TBI to guide future clinical investigations. Medline, Embase, and Scopus were searched for studies that investigated the effect of propranolol on TBI in animal models from inception until June 6, 2023. All routes of administration for propranolol were included and the following outcomes were evaluated: cognitive functions, physiological and immunological responses. Screening and data extraction were done independently and in duplicate. The risk of bias for each individual study was assessed using the SYCLE's risk of bias tool for animal studies. Three hundred twenty-three citations were identified and 14 studies met our eligibility criteria. The data suggests that propranolol may improve post-TBI cognitive and motor function by increasing cerebral perfusion, reducing neural injury, cell death, leukocyte mobilization and p-tau accumulation in animal models. Propranolol may also attenuate TBI-induced immunodeficiency and provide cardioprotective effects by mitigating damage to the myocardium caused by oxidative stress. This systematic review demonstrates that propranolol may be therapeutic in TBI by improving cognitive and motor function while regulating T lymphocyte response and levels of myocardial reactive oxygen species. Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.


Assuntos
Lesões Encefálicas Traumáticas , Propranolol , Propranolol/farmacologia , Propranolol/uso terapêutico , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Humanos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico
11.
Int J Mol Sci ; 25(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38928281

RESUMO

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well-established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within the BLA governs these modulatory effects. However, most current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a low-arousing, hippocampal-dependent task. Our experiments combined a weak object location task (OLT) version with subsequent mild predator odor exposure (POE). To investigate the role of endogenous NA in the BLA in memory modulation, a subset of the animals (Wistar rats) was treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected 90 min after drug infusion or after the OLT test, which was performed 24 h later. We used the obtained samples to estimate the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc)-two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE has the potential to become a valuable behavioral paradigm for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Emoções , Hipocampo , Consolidação da Memória , Norepinefrina , Odorantes , Ratos Wistar , Animais , Consolidação da Memória/fisiologia , Consolidação da Memória/efeitos dos fármacos , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/fisiologia , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Masculino , Ratos , Norepinefrina/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiologia , Hipocampo/efeitos dos fármacos , Emoções/fisiologia , Emoções/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Propranolol/farmacologia
12.
Vasc Health Risk Manag ; 20: 251-254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883398

RESUMO

Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.


Assuntos
Hemangioendotelioma , Propranolol , Sarcoma de Kaposi , Sirolimo , Humanos , Lactente , Masculino , Administração Oral , Biópsia , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/diagnóstico , Propranolol/administração & dosagem , Propranolol/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/patologia , Sirolimo/administração & dosagem , Resultado do Tratamento
13.
Cancer Biol Ther ; 25(1): 2366451, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38857055

RESUMO

BACKGROUND: Chronic stress can induce stress-related hormones; norepinephrine (NE) is considered to have the highest potential in cancer. NE can stimulate the expression of hypoxia-inducible factor-1α (HIF-1α), which is associated with vascular endothelial growth factor (VEGF) secretion and tumor angiogenesis. However, the underlying mechanisms are poorly understood. METHODS: Tumor-bearing mice were subjected to chronic restraint stress and treated with normal saline, human monoclonal VEGF-A neutralizing antibody bevacizumab, or ß-adrenergic receptor (ß-AR) antagonist (propranolol). Tumor growth and vessel density were also evaluated. Human colorectal adenocarcinoma cells were treated with NE, propranolol, or the inhibitor of transforming growth factor-ß (TGF-ß) receptor Type I kinase (Ly2157299) in vitro. TGF-ß1 in mouse serum and cell culture supernatants was quantified using ELISA. The expression of HIF-1α was measured using Real time-PCR and western blotting. Cell migration and invasion were tested. RESULTS: Chronic restraint stress attenuated the efficacy of bevacizumab and promoted tumor growth and angiogenesis in a colorectal tumor model. Propranolol blocked this effect and inhibited TGF-ß1 elevation caused by chronic restraint stress or NE. NE upregulated HIF-1α expression, which was reversed by propranolol or Ly2157299. Propranolol and Ly2157199 blocked NE-stimulated cancer cell migration and invasion. CONCLUSIONS: Our results demonstrate the effect of NE on tumor angiogenesis and the critical role of TGF-ß1 signaling during this process. In addition, ß-AR/TGF-ß1 signaling/HIF-1α/VEGF is a potential signaling pathway. This study also indicates that psychosocial stress might be a risk factor which weakens the efficacy of anti-angiogenic therapy.


Assuntos
Bevacizumab , Neoplasias Colorretais , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neovascularização Patológica , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Animais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Humanos , Neovascularização Patológica/metabolismo , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Propranolol/farmacologia , Linhagem Celular Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Masculino , Movimento Celular , Norepinefrina/farmacologia , Norepinefrina/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Angiogênese , Pirazóis , Quinolinas
14.
J Pharm Biomed Anal ; 248: 116324, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38924878

RESUMO

Since 3D printing technology is an emerging field in pharmaceutical technology, the present study aimed at the development of a mixed-mode liquid chromatographic method for the separation and determination of hydrochlorothiazide, diltiazem, and propranolol to investigate their in-vitro release performance from 3D printed tablets. Due to the unique properties of the mixed-mode stationary phase, the three drugs were separated in less than 8 min under isocratic elution. Method development was accomplished following the Analytical Quality by Design principles and was evaluated using risk assessment and multivariate analysis. The influences of critical method parameters on critical method attributes (were screened using a 2-level fractional factorial design and subsequently optimized through a central composite design. The method operable design region was approved by the establishment of a robust zone using Monte Carlo simulation and capability analysis. The validation of the HPLC method was performed based on the total error concept. The relative bias was varied between ─ 11.6 % and 10.5 % and the RSD values for repeatability and intermediate precision were below 4.4 % in all cases. The limits of detection (LOD) ranged between 0.17 - 0.90 µg/mL and were adequate for the specific application. The developed method was successfully applied to the analysis of the studied drugs in in-vitro drug release samples obtained from 3D-printed tablets combining the above-mentioned active pharmaceutical ingredients (APIs).


Assuntos
Diltiazem , Liberação Controlada de Fármacos , Hidroclorotiazida , Limite de Detecção , Impressão Tridimensional , Propranolol , Comprimidos , Hidroclorotiazida/análise , Hidroclorotiazida/química , Cromatografia Líquida de Alta Pressão/métodos , Diltiazem/análise , Diltiazem/química , Propranolol/análise , Propranolol/química , Reprodutibilidade dos Testes , Tecnologia Farmacêutica/métodos , Método de Monte Carlo , Química Farmacêutica/métodos
15.
Auton Neurosci ; 254: 103194, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38875740

RESUMO

Urinary bladder dysfunction might be related to disturbances at different levels of the micturition reflex arc. The current study aimed to further develop and evaluate a split bladder model for detecting and analysing relaxatory signalling in the rat urinary bladder. The model allows for discrimination between effects at the efferent and the afferent side of the innervation. In in vivo experiments, the stimulation at a low frequency (1 Hz) of the ipsilateral pelvic nerve tended to evoke relaxation of the split bladder half (contralateral side; -1.0 ± 0.4 mN; n = 5), in contrast to high frequency-evoked contractions. In preparations in which the contralateral pelvic nerve was cut the relaxation occurred at a wider range of frequencies (0.5-2 Hz). In separate experiments, responses to 1 and 2 Hz were studied before and after intravenous injections of propranolol (1 mg/kg IV). The presence of propranolol significantly shifted the relaxations into contractions. Also, electrical stimulation of the ipsilateral pudendal nerve evoked relaxations of similar magnitude as for the pelvic stimulations, which were also affected by propranolol. In control in vitro experiments, substances with ß-adrenoceptor agonism, in contrast to a selective α-agonist, evoked relaxations. The current study shows that the split bladder model can be used for in vivo studies of relaxations. In the model, reflex-evoked sympathetic responses caused relaxations at low intensity stimulation. The involvement of ß-adrenoceptors is supported by the sensitivity to propranolol and by the in vitro observations.


Assuntos
Estimulação Elétrica , Propranolol , Nervo Pudendo , Bexiga Urinária , Animais , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia , Bexiga Urinária/efeitos dos fármacos , Nervo Pudendo/fisiologia , Nervo Pudendo/efeitos dos fármacos , Ratos , Propranolol/farmacologia , Feminino , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Ratos Wistar , Pelve/inervação , Antagonistas Adrenérgicos beta/farmacologia , Masculino , Ratos Sprague-Dawley
16.
Biol Pharm Bull ; 47(6): 1123-1127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38839364

RESUMO

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.


Assuntos
Atenolol , Metoprolol , Propranolol , Solubilidade , Cães , Células CACO-2 , Humanos , Animais , Células Madin Darby de Rim Canino , Propranolol/farmacocinética , Metoprolol/farmacocinética , Metoprolol/administração & dosagem , Atenolol/farmacocinética , Atenolol/administração & dosagem , Relação Dose-Resposta a Droga , Biofarmácia/métodos , Permeabilidade , Absorção Intestinal
17.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38848412

RESUMO

CASE: We report a case of an intramuscular thigh hemangioma in a 19-year-old woman with a several year history of atraumatic thigh pain. Radiographs obtained by her primary care physician demonstrated periosteal bone reaction, prompting referral to Orthopaedic Oncology department. The patient had successful symptomatic management with propranolol. CONCLUSION: The case highlights the diagnosis and potential treatments. In a stepwise approach to care for symptomatic benign vascular lesions, propranolol has been a proven therapeutic option and may be a useful first-line therapy for symptomatic hemangiomas.


Assuntos
Hemangioma , Coxa da Perna , Humanos , Feminino , Coxa da Perna/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Adulto Jovem , Neoplasias Musculares/diagnóstico por imagem , Propranolol/uso terapêutico , Radiografia , Antagonistas Adrenérgicos beta/uso terapêutico
19.
BMC Pediatr ; 24(1): 368, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807073

RESUMO

BACKGROUND: Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas. METHODS: A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded. RESULTS: A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported. CONCLUSIONS: This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.


Assuntos
Hemangioma , Neoplasias Labiais , Propranolol , Humanos , Estudos Retrospectivos , Masculino , Feminino , Hemangioma/cirurgia , Neoplasias Labiais/cirurgia , Propranolol/uso terapêutico , Pré-Escolar , Criança , Lactente , Lábio/cirurgia , Resultado do Tratamento , Lipoma/cirurgia
20.
Ecotoxicol Environ Saf ; 279: 116510, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38810284

RESUMO

Microplastics and organic micropollutants are two emerging contaminants that interact with each other in environmental and engineered systems. Sorption of organic micropollutants, such as pharmaceuticals, pesticides and industrial compounds, to microplastics can modify their bioavailability and biodegradation. The present study investigated the capacity of ultra-high density polyethylene particles (125 µm in diameter), before and after aging, to sorb 21 organic micropollutants at different environmentally relevant concentration. Furthermore, the biodegradation of these organic micropollutants by a biofilm microbial community growing on the microplastic surface was compared with the biodegradation by a microbial community originating from activated sludge. Among all tested organic micropollutants, propranolol (70%), trimethoprim (25%) and sotalol (15%) were sorbed in the presence of polyethylene particles. Growth of a biofilm on the polyethylene particles had a beneficial effect on the sorption of bromoxynil, caffeine and chloridazon and on the biodegradation of irbesartan, atenolol and benzotriazole. On the other hand, the biofilm limited the sorption of trimethoprim, propranolol, sotalol and benzotriazole and the biodegradation of 2,4-D. These results showed that ultra-high density polyethylene particles can affect both in a positive and negative way for the abiotic and biotic removal of organic micropollutants in wastewater. This project highlights the need for further investigation regarding the interaction between microplastics and organic micropollutants in the aquatic environment.


Assuntos
Biodegradação Ambiental , Biofilmes , Microplásticos , Polietileno , Propranolol , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Polietileno/química , Adsorção , Trimetoprima , Atenolol , Triazóis/química , Esgotos/química , Esgotos/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA