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1.
Future Med Chem ; 16(17): 1791-1799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39072451

RESUMO

Aim: To identify potential antischistosomal agents through 3D pharmacophore-based virtual screening of US FDA approved drugs.Materials & methods: A comprehensive virtual screening was conducted on a dataset of 10,000 FDA approved drugs, employing praziquantel as a template. Promising candidates were selected and assessed for their impact on Schistosoma mansoni viability in vitro and in vivo using S. mansoni infected mice.Results & conclusion: Among the selected drugs, betamethasone and doxazosin demonstrated in vitro efficacy, with effective concentration 50% (EC50) values ranging from 35 to 60 µM. In vivo studies revealed significant (>50%) reductions in worm burden for both drugs. These findings suggest that betamethasone and doxazosin hold promise for repurposing in treating schistosomiasis. Additionally, the study showcases a useful approach for identifying new antischistosomal drugs.


Discovering new treatments for #schistosomiasis is crucial [Formula: see text]. Our study used virtual screening to identify potential antischistosomal drugs from US FDA approved compounds [Formula: see text]. Promising results in vitro and in vivo. [Formula: see text] #drugdiscovery #tropicaldiseases.


Assuntos
Schistosoma mansoni , United States Food and Drug Administration , Animais , Camundongos , Schistosoma mansoni/efeitos dos fármacos , Estados Unidos , Aprovação de Drogas , Esquistossomicidas/farmacologia , Esquistossomicidas/química , Esquistossomicidas/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Modelos Moleculares , Humanos , Farmacóforo
2.
Radiol Bras ; 57: e20230129, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993967

RESUMO

Objective: To study the effect of antenatal corticosteroid administration on fetal hemodynamics using longitudinal analysis of Doppler waveforms in the umbilical artery (UA) and middle cerebral artery (MCA). Materials and Methods: This was a retrospective study that included 30 fetuses at risk for preterm birth. Twenty-eight pregnant women were treated with betamethasone for fetal lung maturation. Doppler examinations of the UA and MCA were performed once before and three or eight times after corticosteroid administration. We used a Bayesian hierarchical linear model. Reference ranges were constructed, and associations between variables (gestational age and pre-eclampsia) were tested. Results: The mean maternal age, gestational age at betamethasone administration, and gestational age at delivery were 32.6 ± 5.89 years, 30.2 ± 2.59 weeks, and 32.9 ± 3.42 weeks, respectively. On UA Doppler, there was a significant decrease in the pulsatility index (PI) after corticosteroid administration, with a mean of 0.1147 (credibility interval: 0.03687-0.191) in three observations and a median of 0.1437 (credibility interval: 0.02509-0.2627) in eight observations. However, there was no significant change in the Doppler MCA PI, regardless of gestational age and the presence or absence of pre-eclampsia. Conclusion: Although antenatal corticosteroid administration induced a significant decrease in the Doppler UA PI, we observed no change in the cerebral vasculature.


Objetivo: Estudar o efeito da administração antenatal de corticosteroides na hemodinâmica fetal mediante análise longitudinal do Doppler na artéria umbilical (AU) e artéria cerebral média (ACM). Materiais e Métodos: Este foi um estudo retrospectivo que incluiu 30 fetos com risco de nascimento pré-termo. Vinte e oito gestantes foram tratadas com betametasona para maturação pulmonar fetal. Os exames de Doppler da AU e da ACM foram realizados uma vez antes e depois da administração de corticosteroides, num total de três ou oito observações. Utilizamos o modelo linear hierárquico com abordagem Bayesiana. Foram construídos os intervalos de referência e testadas associações entre variáveis (idade gestacional e pré-eclâmpsia). Resultados: A média ± desvio-padrão da idade materna, idade gestacional na administração de betametasona e idade gestacional no parto foram 32,6 ± 5,89 anos, 30,2 ± 2,59 semanas e 32,9 ± 3,42 semanas, respectivamente. No Doppler da AU, verificou-se diminuição significativa do índice de pulsatilidade (IP) com a terapêutica com corticosteroides (média: 0,1147 [0,03687-0,191]; em três observações) (mediana: 0,1437 [0,02509-0,2627]; em oito observações). No entanto, não foi observada alteração significativa no IP do Doppler da ACM, independentemente da idade gestacional e do diagnóstico de pré-eclâmpsia. Conclusão: Os corticosteroides pré-natais induziram diminuição significativa no IP do Doppler da AU, mas não houve alteração na vasculatura cerebral.

3.
Radiol. bras ; Radiol. bras;57: e20230129, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1558820

RESUMO

Abstract Objective: To study the effect of antenatal corticosteroid administration on fetal hemodynamics using longitudinal analysis of Doppler waveforms in the umbilical artery (UA) and middle cerebral artery (MCA). Materials and Methods: This was a retrospective study that included 30 fetuses at risk for preterm birth. Twenty-eight pregnant women were treated with betamethasone for fetal lung maturation. Doppler examinations of the UA and MCA were performed once before and three or eight times after corticosteroid administration. We used a Bayesian hierarchical linear model. Reference ranges were constructed, and associations between variables (gestational age and pre-eclampsia) were tested. Results: The mean maternal age, gestational age at betamethasone administration, and gestational age at delivery were 32.6 ± 5.89 years, 30.2 ± 2.59 weeks, and 32.9 ± 3.42 weeks, respectively. On UA Doppler, there was a significant decrease in the pulsatility index (PI) after corticosteroid administration, with a mean of 0.1147 (credibility interval: 0.03687-0.191) in three observations and a median of 0.1437 (credibility interval: 0.02509-0.2627) in eight observations. However, there was no significant change in the Doppler MCA PI, regardless of gestational age and the presence or absence of pre-eclampsia. Conclusion: Although antenatal corticosteroid administration induced a significant decrease in the Doppler UA PI, we observed no change in the cerebral vasculature.


Resumo Objetivo: Estudar o efeito da administração antenatal de corticosteroides na hemodinâmica fetal mediante análise longitudinal do Doppler na artéria umbilical e artéria cerebral média (ACM). Materiais e Métodos: Este foi um estudo retrospectivo que incluiu 30 fetos com risco de nascimento pré-termo. Vinte e oito gestantes foram tratadas com betametasona para maturação pulmonar fetal. Os exames de Doppler da AU e da ACM foram realizados uma vez antes e depois da administração de corticosteroides, num total de três ou oito observações. Utilizamos o modelo linear hierárquico com abordagem Bayesiana. Foram construídos os intervalos de referência e testadas associações entre variáveis (idade gestacional e pré-eclâmpsia). Resultados: A média ± desvio-padrão da idade materna, idade gestacional na administração de betametasona e idade gestacional no parto foram 32,6 ± 5,89 anos, 30,2 ± 2,59 semanas e 32,9 ± 3,42 semanas, respectivamente. No Doppler da AU, verificou-se diminuição significativa do índice de pulsatilidade (IP) com a terapêutica com corticosteroides (média: 0,1147 [0,03687-0,191]; em três observações) (mediana: 0,1437 [0,02509-0,2627]; em oito observações). No entanto, não foi observada alteração significativa no IP do Doppler da ACM, independentemente da idade gestacional e do diagnóstico de pré-eclâmpsia. Conclusão: Os corticosteroides pré-natais induziram diminuição significativa no IP do Doppler da AU, mas não houve alteração na vasculatura cerebral.

4.
Steroids ; 193: 109202, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36828350

RESUMO

Epilepsy is a chronic disease characterized by an ongoing predisposition to seizures. Although inflammation has emerged as a crucial factor in the etiology of epilepsy, no approaches to anti-inflammatory treatment have been clinically proven to date. Betamethasone (a corticosteroid drug used in the clinic for its anti-inflammatory and immunosuppressive effects) has never been evaluated in attenuating the intensity of seizures in a kindling animal model of seizures. Using a kindling model in male wistar rats, this study evaluated the effect of betamethasone on the severity of seizures and levels of pro-inflammatory interleukins. Seizures were induced by pentylenetetrazole (30 mg/kg) on alternate days for 15 days. The animals were divided into four groups: a control group treated with saline, another control group treated with diazepam (2 mg/kg), and two groups treated with betamethasone (0.125 and 0.250 mg/kg, respectively). Open field test was conducted. Betamethasone treatments were effective in reducing the intensity of epileptic seizures. There were lower levels of Tumor Necrosis Factor-α and interleukin-1ß in the cortex, compared to the saline group, on the other hand, levels in the hippocampus remained similar to the control groups. There was no change in the levels of interleukin-6 in the evaluated structures. Serum inflammatory mediators remained similar. Lower quantities of inflammatory mediators in the central nervous system may have been the key to the reduced severity of seizures on the Racine scale.


Assuntos
Betametasona , Epilepsia , Ratos , Animais , Masculino , Betametasona/efeitos adversos , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Epilepsia/tratamento farmacológico , Ratos Wistar , Anti-Inflamatórios/uso terapêutico , Mediadores da Inflamação/efeitos adversos , Modelos Animais de Doenças , Anticonvulsivantes/efeitos adversos
5.
J Appl Toxicol ; 43(5): 752-763, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36511433

RESUMO

Betamethasone (BM) is the drug of choice for antenatal corticosteroid therapy for women at risk of preterm delivery because it induces fetal lung maturation and enhances survival after birth. However, our group reported evidence of fetal programming and impaired reproductive development and function in rats exposed during the critical window of genital system development. Therefore, we aimed to investigate the effects of BM on the sexual development of rats in the period that corresponds to antenatal corticosteroid therapy in humans. Male and female rats were exposed subcutaneously to BM at 0.1 µg/g of pups' body weight or to a NaCl 0.9% solution (control) on postnatal days 1-3. It was observed that neonatal exposure to BM decreased body weight and weight gain in male and female rats during treatment. The estrous cycle was deregulated and LH level was decreased in female rats. In male rats, the sperm concentration in the caput-corpus of the epididymis was decreased, whereas the sperm transit time and sperm concentration in the cauda of the epididymis were increased. Our results demonstrated that neonatal exposure to BM impaired body growth of male and female rats, deregulated the estrous cycle of female rats, and altered sperm quality of male rats. Therefore, BM exposure from postnatal days 1 to 3 corroborated results previously observed after prenatal exposure to this drug. Despite the recognized importance of human antenatal corticosteroid therapy, the findings of this study should encourage further studies in order to minimize possible adverse postnatal effects.


Assuntos
Betametasona , Sêmen , Feminino , Masculino , Ratos , Gravidez , Humanos , Animais , Betametasona/toxicidade , Reprodução , Corticosteroides/farmacologia , Peso Corporal
6.
Braz. J. Pharm. Sci. (Online) ; 59: e20314, 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1447570

RESUMO

Abstract Betamethasone (BET) is a synthetic glucocorticoid recommended for pregnant women at imminent risk of preterm birth before 34 weeks to reduce neonatal complications. There are different techniques to describe BET plasma quantification. However, none quantified the plasmatic concentration of BET in dichorionic (DC) twin pregnancies using LC-MS. Our objectives were to develop and validate a method for quantifying BET by LC-MS for pharmacokinetic (PK) and placental transfer studies in DC twin pregnancies. Blood samples were collected after intramuscular administration of a single BET dose containing 6 mg disodium phosphate + 6 mg acetate. BET was determined in plasma by liquid-liquid extraction. The method showed linearity in the range of 2-250 ng/mL, as well as precision and accuracy with a coefficient of variation and relative standard errors ≤ 15%. Additionally, the method presented selectivity and did not present matrix or carry-over effect. Stability tests also presented coefficient of variation and relative standard errors ≤ 15%. This is the first study which describe maternal and fetal plasma concentrations of BET in a DC twin pregnancy. The BET PK parameters were AUC0-∞, CL/F, Vd/F, Cmax, Tmax of 292.20 h*ng/mL, 39.08 L/h, 278.72 L, 25.55 ng/mL and 0.58 h, respectively. The placental transfer ratios of umbilical vein/maternal vein and intervillous space/maternal vein were 0.14 and 0.19 and 0.40 and 0.27 for both twins, respectively. However, a clinical study with more subjects is imperative to confirm this higher concentration of BET in the intervillous space


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Plasma/metabolismo , Betametasona/antagonistas & inibidores , Extração Líquido-Líquido/instrumentação
7.
AIMS Neurosci ; 9(3): 320-344, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329900

RESUMO

During prenatal life, exposure to synthetic glucocorticoids (SGCs) can alter normal foetal development, resulting in disease later in life. Previously, we have shown alterations in the dendritic cytoarchitecture of Purkinje cells in adolescent rat progeny prenatally exposed to glucocorticoids. However, the molecular mechanisms underlying these alterations remain unclear. A possible molecular candidate whose deregulation may underlie these changes is the glucocorticoid receptor (GR) and neurotrophin 3/ tropomyosin receptor kinase C, neurotrophic complex (NT-3/TrkC), which specifically modulates the development of the neuronal connections in the cerebellar vermis. To date, no evidence has shown that the cerebellar expression levels of this neurotrophic complex are affected by exposure to a synthetic glucocorticoid in utero. Therefore, the first objective of this investigation was to evaluate the expression of GR, NT-3 and TrkC in the cerebellar vermis using immunohistochemistry and western blot techniques by evaluating the progeny during the postnatal stage equivalent to adolescence (postnatal Day 52). Additionally, we evaluated anxiety-like behaviours in progeny using the elevated plus maze and the marble burying test. In addition, an environmental enrichment (EE) can increase the expression of some neurotrophins and has anxiolytic power. Therefore, we wanted to assess whether an EE reversed the long-term alterations induced by prenatal betamethasone exposure. The major findings of this study were as follows: i) prenatal betamethasone (BET) administration decreases GR, NT-3 and TrkC expression in the cerebellar vermis ii) prenatal BET administration decreases GR expression in the cerebellar hemispheres and iii) enhances the anxiety-like behaviours in the same progeny, and iv) exposure to an EE reverses the reduced expression of GR, NT-3 and TrkC in the cerebellar vermis and v) decreases anxiety-like behaviours. In conclusion, an enriched environment applied 18 days post-weaning was able to restabilize GR, NT-3 and TrkC expression levels and reverse anxious behaviours observed in adolescent rats prenatally exposed to betamethasone.

8.
Rev. bras. ginecol. obstet ; Rev. bras. ginecol. obstet;44(3): 304-310, Mar. 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1387875

RESUMO

Abstract Objective To review data on the use of corticosteroids for the treatment of fetuses with high-risk congenital pulmonary adenomatoid malformation (CPAM). Methods Integrative review based on the literature available onMEDLINE and LILACS, including articles published until November, 2020. Results The initial search resulted in 87 articles, 4 of which were selected for analysis, with all of them being retrospective descriptive observational studies. In the group of fetuses that received only a single corticosteroid cycle, the hydrops resolution rate was 70%, and the survival rate was 83.8%. In fetuses treated with 2 or more cycles of corticosteroids, there was an improvement in the condition of hydrops or edema in a single body compartment in 47%, and survival of 81.8% of the fetuses. Conclusion The use of corticosteroids for the prenatal treatment of high-risk CPAM appears to be associated with an improvement in perinatal outcomes.


Resumo Objetivo Revisar os dados sobre o uso de corticoide no tratamento de fetos com malformação adenomatoide pulmonar congênita (MAPC) de alto risco. Métodos Revisão integrativa com base na literatura disponível no MEDLINE e LILACS, incluindo artigos publicados até novembro de 2020. Resultados A busca inicial resultou em 87 artigos, dos quais 4 foram selecionados para análise, todos tratando-se de estudos observacionais descritivos retrospectivos. No grupo de fetos que recebeu apenas um único ciclo de corticosteroide, a taxa de resolução da hidropsia foi de 70% e a taxa de sobrevida de 83,8%. Emfetos tratados com 2 ou mais ciclos de corticosteroides, houve melhora do quadro de hidropsia ou edema em um único compartimento corporal em 47% dos fetos e taxa de sobrevida de 81,8%. Conclusão O uso de corticosteroides para o tratamento pré-natal da MAPC de alto risco parece estar associado à melhora dos resultados perinatais.


Assuntos
Humanos , Feminino , Gravidez , Betametasona , Malformação Adenomatoide Cística Congênita do Pulmão , Corticosteroides , Edema , Feto/anormalidades
9.
J Dermatolog Treat ; 33(2): 875-877, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32594786

RESUMO

BACKGROUND: Betamethasone can be used for intralesional infiltration, but there is little evidence in the literature to indicate its effectiveness in alopecia areata. OBJECTIVE: To assess the safety and effectiveness of the use of different doses of intralesional betamethasone, when compared to triamcinolone acetonide for the treatment of alopecia areata. METHODS: We recruited 12 patients with alopecia patch divided into four quadrants. Each quadrant, after randomization, received an intralesional injection with one of the following treatments: triamcinolone acetonide 2.5 mg/ml, betamethasone 0.375 mg/ml, betamethasone 1.75 mg/ml, or 0.9% saline (placebo). The intervention was repeated in the same quadrant every 4 weeks, totaling 3 sessions. Visual and dermoscopic evaluation of the results were performed. Trial registration: ReBec RBR-5kyg2r. RESULTS: At 4 and 8 weeks of intervention, triamcinolone acetonide 2.5 mg/ml provided the best visual results. Nevertheless, at the end of the study, the best visual results were seen with both triamcinolone acetonide and betamethasone 1.75 mg/ml, with significant difference when compared to betamethasone 0.375 mg/ml and placebo (p=.0489 and <.0001, respectively). There was a progressive reduction in the number of dystrophic hairs in all quadrants. CONCLUSION: Triamcinolone acetonide shows earlier results in repilation, but at 12 weeks betamethasone 1.75 mg/ml had similar results.


Assuntos
Alopecia em Áreas , Triancinolona Acetonida , Alopecia em Áreas/tratamento farmacológico , Betametasona/uso terapêutico , Humanos , Injeções Intralesionais , Resultado do Tratamento , Triancinolona Acetonida/uso terapêutico
10.
Br J Clin Pharmacol ; 88(4): 1897-1903, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34665470

RESUMO

AIM: No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone pharmacokinetic parameters in singleton and dichorionic (DC) and monochorionic twin pregnancies in the third trimester of pregnancy. METHODS: Twenty-six pregnant women received 2 intramuscular doses of 6 mg of betamethasone sodium phosphate plus 6 mg betamethasone acetate due to preterm labour. Serial blood samples were collected for 24 hours after the first intramuscular dose of betamethasone esters. Betamethasone plasma concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry analytical method, and the pharmacokinetic parameters were obtained employing a noncompartmental model. Preliminary data on the betamethasone placental transfer are also presented. RESULTS: The geometric mean (95% confidence interval) of AUC0-∞ 645.1 (504.3-825.2) vs. 409.8 (311.2-539.6) ng.h/mL and CL/F 17.70 (13.84-22.65) vs. 27.87 (21.17-36.69) were significantly different, respectively, in singleton pregnancies when compared to DC twins. CONCLUSION: Data from this study suggest that the presence of 2 foetoplacental units may increase the betamethasone metabolism by hepatic CYP3A4 and/or placental 11ß-HSD2 enzymes. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether these betamethasone pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.


Assuntos
Betametasona , Gravidez de Gêmeos , Córion , Feminino , Humanos , Recém-Nascido , Placenta , Gravidez , Terceiro Trimestre da Gravidez
11.
Braz. J. Pharm. Sci. (Online) ; 58: e20262, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1403757

RESUMO

Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.


Assuntos
Animais , Masculino , Ratos , Fibrose Oral Submucosa/tratamento farmacológico , Betametasona/análise , Dexametasona/análise , Físico-Química/classificação , Benchmarking/métodos , Géis/classificação , Adesividade , Liberação Controlada de Fármacos
12.
Rev. bras. reprod. anim ; 46(4): 336-339, out.-dez. 2022.
Artigo em Português | VETINDEX | ID: biblio-1414961

RESUMO

Dentre as mais importantes causas de morbidade neonatal na prematuridade, destacam-se os distúrbios respiratórios, complicações infecciosas, instabilidade crítica da termorregulação, inabilidade para homeostase energética e falhas na transferência de imunidade passiva. Dentre os problemas de origem pulmonar intimamente relacionados à prematuridade, destaca-se a imaturidade pulmonar por deficiência de surfactante, evoluindo para diminuição da capacidade pulmonar, hipoxemia, hipercapnia e acidose. Os neonatos caninos prematuros apresentam baixa vitalidade, hipotermia, bradipnéia, irregularidade do padrão respiratório, reduzido tônus e responsividade neuro-muscular. As áreas do parênquima pulmonar para efetuar trocas gasosas são limitadas em filhotes prematuros, culminando em alterações do equilíbrio ácidobase. Além disto, os recém-nascidos prematuros apresentam instabilidade energética e falha de transferência de imunidade passiva. Como medida preventiva à morbidade do neonato prematuro, indicase a corticoterapia pré-natal 48 horas antes do parto em cadelas gestantes, induzindo a maturidade funcional do pulmão fetal, além de melhorar a vitalidade e evolução clínica neonatal. Ademais, a corticoterapia antenatal estimula a transferência placentária de imunoglobulinas e absorção de imunoglobulinas colostrais, bem como aumenta a capacidade glicogênica. Nos casos emergenciais, preconiza-se medidas intensivas aos recém-nascidos prematuros, as quais incluem: reanimação respiratória, controle da hipotermia, reposição glicêmica na hipoglicemia e controle imunológico da falha de transferência imune passiva.(AU)


Among the most important causes of neonatal morbidity in prematurity, respiratory disorders, infectious complications, critical instability of thermoregulation, inability for energy homeostasis and failures in the transfer of passive immunity stand out. Among the problems of pulmonary origin closely related to prematurity, pulmonary immaturity due to surfactant deficiency stands out, evolving to decreased lung capacity, hypoxemia, hypercapnia and acidosis. Premature canine neonates have low vitality, hypothermia, bradypnea, irregular breathing pattern, reduced tone and neuromuscular responsiveness. The areas of the lung parenchyma to carry out gas exchange are limited in premature pups, culminating in changes in acid-base balance. In addition, premature newborns have energetic instability and failure to transfer passive immunity. As a preventive measure against premature neonate morbidity, prenatal corticosteroid therapy is indicated 48 hours before delivery in pregnant bitches, inducing functional maturity of the fetal lung, in addition to improving neonatal vitality and clinical evolution. Furthermore, antenatal corticosteroid therapy stimulates the placental transfer of immunoglobulins and the absorption of colostral immunoglobulins, as well as increasing the glycogenic capacity. In emergency cases, intensive measures are recommended for premature newborns, which include: respiratory resuscitation, hypothermia control, glycemic replacement in hypoglycemia and immunological control of passive immune transfer failure.(AU)


Assuntos
Animais , Cães/embriologia , Animais Recém-Nascidos/fisiologia , Tensoativos/análise , Betametasona/análise
13.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072090

RESUMO

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.


Assuntos
Alginatos/química , Betametasona/administração & dosagem , Portadores de Fármacos , Hidrogéis/química , Metacrilatos/química , Polímeros/química , Alicerces Teciduais/química , Animais , Técnicas de Cultura de Células , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Condrócitos , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Hidrogéis/síntese química , Cinética , Camundongos , Estrutura Molecular , Análise Espectral
14.
Medicentro (Villa Clara) ; 24(4): 721-734, oct.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1143241

RESUMO

RESUMEN Introducción: el empleo de corticoesteroides es una estrategia eficaz para reducir el dolor postoperatorio. Objetivo: determinar la utilidad de la betametasona en la prevención del dolor postoperatorio en pacientes intervenidos por hernia discal lumbar. Métodos: se realizó un estudio cuasi-experimental en 100 pacientes intervenidos por hernia discal lumbar en el Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro¼, de la provincia de Villa Clara, durante el período de abril de 2013 a diciembre de 2015. Se dividieron en un grupo control y en un grupo estudio; previo a la incisión quirúrgica, se les administró diclofenaco 75 mg endovenoso y 8 mg de betametasona (solo en el grupo estudio). Resultados: el 70 % de los pacientes eran masculinos, y la edad media fue 45,99 años. En el grupo estudio el tiempo de aparición del dolor () y su intensidad, a las 4, 8 y 24 horas, fue significativamente menor que en el grupo control (pα< 0,010, pα< 0,001 y <0,001); el 48 % de los pacientes pudieron levantarse sin dolor, 32 % menos requirieron analgesia de rescate, y el grado de satisfacción fue significativamente mejor. Conclusiones: la administración de betametasona antes de la incisión quirúrgica resultó muy útil en la prevención del dolor postoperatorio en los pacientes intervenidos de hernia discal lumbar.


ABSTRACT Introduction: use of corticosteroids is an effective strategy to reduce postoperative pain. Objective: to determine usefulness of betamethasone in the prevention of postoperative pain in patients operated for lumbar disc herniation. Methods: a quasi-experimental study was carried out in 100 patients operated for lumbar disc herniation at "Arnaldo Milián Castro" Clinico-Surgical University Hospital, in Villa Clara province from April 2013 to December 2015. They were divided into a control group and a study one; prior to surgical incision, intravenous diclofenac 75mg and betamethasone 8mg were administered (only in the study group). Results: 70% of the patients were male, and the mean age was 45.99 years. In the study group, the time of onset of pain () and its intensity, at 4, 8 and 24 hours, was significantly lower than in the control group (pα <0.010, pα <0.001 and <0.001); 48% of the patients were able to get up without pain, 32 % less required rescue analgesia, and the degree of satisfaction was significantly better. Conclusions: administration of betamethasone before surgical incision was very useful in the prevention of postoperative pain in patients operated for lumbar disc herniation.


Assuntos
Dor Pós-Operatória , Betametasona , Hérnia , Vértebras Lombares
15.
Theriogenology ; 153: 19-26, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417607

RESUMO

Among prematurity complications, the most important disorder is structural immaturity and inadequate production of pulmonary surfactant. Betamethasone is the drug of choice to artificially improve pulmonary capacity, thus we aimed to verify the effect of prenatal maternal treatment on lung development of premature puppies. Pregnant bitches were allocated in Term Group (n = 7), Preterm-Treated Group (interrupted pregnancies with maternal administration of betamethasone; n = 7), Preterm-Control Group (untreated interrupted pregnancies; n = 7), Extremely-Preterm Group (interrupted pregnancies at 55d; n = 6). Puppies were subjected to chest radiographic at birth, morphometric description of pulmonary structures and immunohistochemical analysis of surfactant protein B, proliferating cell nuclear antigen and cytokeratin were performed. In Preterm-Treated Group it was possible to more clearly identify cardiac silhouette and lung parenchyma by X-Ray. Saccular formation was higher in Preterm Groups, while Term Group had higher subsaccular development. Lung septation was higher in Treated and Term Groups. Term Group had higher number of cells marked for SP-B, whereas higher proliferation was observed in Extreme-Preterm and Preterm-Control Groups. Preterm Treated and Term Groups had higher tissue differentiation. In conclusion, antenatal maternal corticotherapy in dogs acted by increasing lung morphology and development of areas of gas exchange, regulate metabolism of pulmonary fluids rather than stimulate surfactant production.


Assuntos
Betametasona/uso terapêutico , Pneumopatias/veterinária , Pulmão/efeitos dos fármacos , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cães , Feminino , Imuno-Histoquímica , Pulmão/patologia , Pneumopatias/prevenção & controle , Gravidez , Nascimento Prematuro , Radiografia Torácica/veterinária
16.
Braz. J. Pharm. Sci. (Online) ; 56: e18077, 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1089226

RESUMO

Intralesional corticosteroid injection (ICSI) is known as one of the main methods used for treating a wide range of lesions. It also results in a high concentration of drugs at lesion sites, with minimal systemic absorption. Thus, this study aimed to provide a review of the intralesional corticosteroid injection (ICSI) indications in the treatment of oral lesions. To this end; relevant key words were searched in the databases of PubMed, Google Scholar, Scopus, ScienceDirect, and UpToDate in the present study. Accordingly, the results of a total number of 62 case reports or case series articles were used in this study and the positive therapeutic effects of intralesional corticosteroid injection (ICSI) in 23 common oral lesions were reported. The most common type of intralesional steroid in the treatment of oral lesions was triamcinolone. No significant difference was also observed in terms of pain in patients following the use of steroid alone or in combination with anesthetic agents; moreover, the reported side effects of this method were exceptionally rare and transient. It was concluded that the intralesional corticosteroid injection (ICSI) could be one of the effective therapeutic methods with no significant problems in many oral lesions such as inflammatory, immunologic, and vascular ones due to its higher therapeutic effects than other topical forms of steroids and fewer side effects than systemic corticosteroid.

17.
Andrology ; 7(5): 719-729, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31250541

RESUMO

BACKGROUND: Studies on epididymal toxicology are scarce. Betamethasone (BM) is a glucocorticoid used in clinical practice for antenatal therapy. We previously reported changes to testicular morphology, altered sperm quality, and fertility in adult rats following intrauterine administration of BM. OBJECTIVES: Given that high levels of corticosteroids during gestation lead to fetal androgen depletion, and the essential role of testosterone during epididymal development, here we investigated epididymal morphology and physiology in the F1 and F2 male offspring of female rats treated with BM during gestation. MATERIALS AND METHODS: Pregnant rats were randomly divided into two experimental groups: control (saline vehicle, n = 11) and BM-treated group (0.1 mg/kg betamethasone 21-phosphate disodium, n = 13). Rats received an intramuscular injection of vehicle or BM on gestational days 12, 13, 18, and 19. This encompasses the beginning of the critical window of male rat reproductive tract development. A subset of three males from each litter (n = 5 litters/group) was used: One rat per litter was euthanized at puberty, one was euthanized at adulthood, while the others were mated with a non-treated female to obtain the F2 generation. The same protocol described for the F1 was applied for F2, except for the mating protocol. RESULTS: In both F1 and F2 generations, prenatal BM exposure resulted in delayed differentiation of the cauda epididymal epithelium, characterized by increased cribriform appearance on PND 45, and displayed weaker or non-detectable Cx43 immunostaining. Furthermore, in the F1 generation only, immunostaining of TP63, a transcription factor expressed in basal cells, appeared more intense with a greater number of TP63-positive cells observed in the cauda epididymis. In adults, the epithelial area was reduced in the F1 BM rats. The contractile activity of isolated epididymal ducts was comparable between groups. DISCUSSION AND CONCLUSION: Prenatal BM exposure leads to intergenerational impairment in the development and structure of the rat epididymis.


Assuntos
Betametasona/toxicidade , Epididimo/crescimento & desenvolvimento , Epididimo/fisiologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Animais , Conexina 43/metabolismo , Feminino , Masculino , Gravidez , Ratos , Ratos Wistar , Maturação do Esperma/efeitos dos fármacos , Testosterona/sangue , Proteínas Supressoras de Tumor/metabolismo
18.
Arch Soc Esp Oftalmol (Engl Ed) ; 94(7): 347-351, 2019 Jul.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30846248

RESUMO

Nummular keratitis is an inflammatory process of the cornea that is characterised by multiple sub-epithelial deposits, for which a variety of therapeutic approaches have been proposed. A retrospective review was performed using the medical records of patients diagnosed with nummular keratitis and treated with a combined intrastromal injection of ganciclovir and depot betamethasone between the years 2009 and 2017. A total of 21 eyes of 16 patients were finally included. Upon termination of the treatment, 18 eyes (85.71%) were asymptomatic. This improvement was maintained during a mean follow-up time of 22.90 months. Depot betamethasone mixed with ganciclovir by intrastromal application is a good alternative for the treatment of nummular keratitis.


Assuntos
Betametasona/uso terapêutico , Ganciclovir/uso terapêutico , Ceratite/tratamento farmacológico , Adulto , Idoso , Betametasona/administração & dosagem , Substância Própria , Preparações de Ação Retardada , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Ganciclovir/administração & dosagem , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Rev. chil. obstet. ginecol. (En línea) ; Rev. chil. obstet. ginecol;84(1): 41-48, feb. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1003721

RESUMO

RESUMEN Introducción: El estándar para inducción de madurez pulmonar en fetos con riesgo de nacer prematuramente es la administración de 12 mg de betametasona acetato/fosfato por dos veces espaciada cada 24 horas. El uso establecido en algunos hospitales públicos en Chile es con dos dosis de 12 mg betametasona fosfato aunque no existen estudios publicados sólo con betametasona fosfato sobre la incidencia de Síndrome de Distress Respiratorio (SDR). Objetivo: Evaluar efecto de betametasona en su forma fosfato como tratamiento antenatal para inducción de madurez fetal pulmonar en la incidencia SDR debido a membrana hialina en prematuros menores de 34 semanas de edad gestacional. Comparar el efecto de betametasona fosfato con el efecto publicado de betametasona acetato/fosfato. Material y método: Análisis de incidencia de SDR en prematuros nacidos en Hospital Padre Hurtado entre 24+0 y 34+0 semanas que recibieron betametasona fosfato para madurez pulmonar y aquellos que no la recibieron. Resultados: De 1.265 neonatos estudiados, 722 completaron dos dosis (57,5%); 436 sólo una dosis (34,5%) y 107 (8,5%) no recibieron corticoides antenatales. La incidencia de SDR debido a membrana hialina en el grupo con dos dosis fue 8,7%, una dosis 25,3% y 32,7% en los no tratados (p<0,001). Para SDR severo las incidencias fueron 6,7%, 12,6% y 16,8% respectivamente (p<0,001). Conclusiones: Inducción de madurez fetal pulmonar con betametasona fosfato en dos dosis de 12 mg IM separadas por 24 horas otorga una reducción significativa de incidencia de SDR semejante a la publicada con betametasona acetato/fosfato en iguales dosis.


ABSTRACT The standard for induction of lung maturity in fetuses at risk of being born prematurely is the administration of 12 mg of betamethasone acetate/phosphate two doses separated by 24 hours. The established use in some public hospitals in Chile is with two doses of 12 mg betamethasone phosphate although there are no studies published with betamethasone phosphate alone on the incidence of respiratory distress syndrome (RDS). Objective: To evaluate the effect of betamethasone in its phosphate form as antenatal treatment for the induction of fetal lung maturity in the incidence of RDS due to hyaline membrane in preterm infants less than 34 weeks of gestational age. To compare the effect of betamethasone phosphate with the published effect of betamethasone acetate/phosphate. Material and method: Analysis of the incidence of RDS in preterm infants born at Hospital Padre Hurtado between 24 + 0 and 34 + 0 weeks who received betamethasone phosphate for lung maturity and those who did not receive it. Results: Of 1,265 infants studied, 722 completed two doses (57.5%); 436 only one dose (34.5%) and 107 (8.5%) did not receive antenatal corticosteroids. The incidence of RDS due to hyaline membrane in the group with two doses was 8.7%, one dose 25.3% and 32.7% in the untreated ones (p <0.001). For severe RDS, incidences were 6.7%, 12.6% and 16.8% respectively (p <0.001). Conclusions: Induction of fetal lung maturity with betamethasone phosphate in two doses of 12 mg IM separated by 24 hours gives a significant reduction in the incidence of RDS similar to that published with betamethasone acetate/phosphate in equal doses.


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle , Betametasona/análogos & derivados , Nascimento Prematuro , Glucocorticoides/administração & dosagem , Cuidado Pré-Natal/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Betametasona/administração & dosagem , Incidência , Estudos Retrospectivos , Hospitais Públicos , Doença da Membrana Hialina/prevenção & controle , Pulmão/efeitos dos fármacos
20.
Eur J Obstet Gynecol Reprod Biol ; 234: 32-37, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639954

RESUMO

OBJECTIVE: The purpose of this review is to describe the historical and scientific basis of antenatal corticosteroids (ACS) therapy, to improve the management of preterm birth and decreasing rates of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis and perinatal mortality in premature infants. STUDY DESIGN: We searched MEDLINE/PubMed electronic database, the Cochrane Library, using medical subheading search words such as "ACS", "corticosteroids", "betamethasone" or "dexamethasone", matching with "preterm birth". RESULTS: This practice was initiated by Liggins and Howie in 1972 and is supported by the initial comprehensive meta-analysis of Crowley, Chambers and Keirse, in 1990, the NIH Consensus Development Conference in 1994, the second Consensus Conference to evaluate repeated courses of corticosteroids in 2000 and the practice recommendations of obstetric societies worldwide. ACS therapy before anticipated preterm birth is one of the most important antenatal therapies and an important evidence-based practice for reducing mortality, and decreasing rates of complications in premature infants. CONCLUSIONS: Today, there is no controversy that women with preterm birth <34 weeks should be ACS treated. Actually, rescue courses are recommended; while multiple, serial, repeated or weekly courses, are not recommended. In any clinical conditions, as preterm premature rupture of membranes, multiple pregnancies, severe preeclampsia/HELLP syndrome and fetal growth restriction; ACS is recommended.


Assuntos
Corticosteroides/administração & dosagem , Betametasona/administração & dosagem , Dexametasona/administração & dosagem , Nascimento Prematuro/tratamento farmacológico , Corticosteroides/efeitos adversos , Animais , Betametasona/efeitos adversos , Conferências de Consenso como Assunto , Dexametasona/efeitos adversos , Feminino , Maturidade dos Órgãos Fetais/efeitos dos fármacos , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/prevenção & controle , Pulmão/embriologia , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
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