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Objectives: This study aimed to make a bibliographic update on the already published data on bumetanide, addressing the main information on its use in Autism Spectrum Disorder (ASD). Methods: This was an integrative narrative review in which the following databases were used: Web of Science, MEDLINE, ScienceDirect, and Scielo. The descriptors used were: Autism Spectrum Disorder, Autistic Disorder and Bumetanide. It was considered only articles published in English and French. Original articles, randomized clinical trials, case reports, and review articles were included. Results: The results show that the use of bumetanide alters regions of the brain linked to the positive development of language, improvement of visual contact, improvement in social interactions, among others. Studies are also concerned about the safety and efficacy of bumetanide in ASD since several adverse effects have been reported. The most frequent were hypokalemia, polyuria, and loss of appetite. Conclusion: Bumetanide has proven as effective in improving some important symptoms in ASD, especially linked to language and social interaction, however, studies with larger groups of patients and with longer treatment and observation time are needed to confirm the efficacy and clarify the safety profile in use for people with ASD.
Objetivo: O objetivo deste trabalho foi fazer uma atualização bibliográfica sobre os dados já publicados da bumetanida, abordando as principais informações sobre seu uso no Transtorno do Espectro Autista (TEA). Metodologia: Foi realizada uma revisão do tipo narrativa integrativa, da qual foram utilizadas as bases de dados: Web of Science, MEDLINE, ScienceDirect e Scielo, com a utilização dos seguintes descritores: Autism Spectrum Disorder, Autistic Disorder e Bumetanide. Foram considerados apenas artigos publicados nas línguas inglesa e francesa. Foram incluídos artigos originais, ensaios clínicos randomizados e relatos de caso. Foram excluídos artigos de revisão. Resultados: Os resultados mostram que o uso da bumetanida altera regiões do cérebro ligadas ao desenvolvimento positivo da linguagem, melhora do contato visual, melhora nas interações sociais, entre outros. Os estudos também se preocupam em relacionar a segurança e a eficácia da bumetanida no TEA, do qual foram relatados diversos efeitos adversos, sendo os mais frequentes a hipocalemia, a poliúria e a perda de apetite. Conclusão: A bumetanida mostrou ser eficaz na melhoria de alguns importantes sintomas no TEA, especialmente ligados à linguagem e interação social, entretanto, estudos com grupos maiores de pacientes e com maior tempo de tratamento e observação são necessários para confirmar a eficácia e esclarecer o perfil de segurança no uso para pessoas com TEA.
: Este estudio tuvo como objetivo realizar una actualización bibliográfica sobre los datos ya publicados sobre la bumetanida, abordando la principal información sobre su uso en el Trastorno del Espectro Autista (TEA). Métodos: Se trata de una revisión narrativa integradora en la que se utilizaron las siguientes bases de datos: Web of Science, MEDLINE, ScienceDirect y Scielo. Los descriptores utilizados fueron: Trastorno del Espectro Autista, Trastorno Autista y Bumetanida. Se consideraron sólo los artículos publicados en inglés y francés. Se incluyeron artículos originales, ensayos clínicos aleatorios, informes de casos y artículos de revisión. Resultados: Los resultados muestran que el uso de la bumetanida altera regiones del cerebro relacionadas con el desarrollo positivo del lenguaje, la mejora del contacto visual, la mejora de las interacciones sociales, entre otros. Los estudios también se preocupan por la seguridad y eficacia de la bumetanida en el TEA, ya que se han reportado varios efectos adversos. Los más frecuentes fueron la hipocalemia, la poliuria y la pérdida de apetito. Conclusiones: La bumetanida ha demostrado ser eficaz en la mejora de algunos síntomas importantes en el TEA, especialmente vinculados al lenguaje y la interacción social, sin embargo, se necesitan estudios con grupos más grandes de pacientes y con mayor tiempo de tratamiento y observación para confirmar la eficacia y aclarar el perfil de seguridad en el uso para personas con TEA.
Subject(s)
Autistic Disorder/drug therapy , Bumetanide/adverse effects , Bumetanide/pharmacology , Autism Spectrum Disorder/drug therapy , Appetite Depressants/antagonists & inhibitors , Polyuria , Drug-Related Side Effects and Adverse Reactions , Social Interaction/drug effects , Language DevelopmentABSTRACT
Background: Autism spectrum disorders (ASD) is diagnosed primarily by the presence of impaired social interaction, social communication, and stereotypical behaviors. Bumetanide, a loop diuretic which acts by inhibiting Na+-K+-2Cl co-transporters (NKCC): NKCC1 and NKCC2 are explored as a pharmacological agent for treatment of ASD. Aim and Objectives: The aim of the study was to analyze safety and efficacy of bumetanide in treatment of ASD. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Autism” AND “Bumetanide.” Randomized or cross-over trials comparing efficacy of bumetanide versus placebo in ASD patients of any age group were included in analysis. Quantity of reduction in total Childhood Autism Rating Scale (CARS) score after 90 days of treatment with bumetanide was the primary outcome measure analyzed. Efficacy outcome measures were estimated by calculating the Mean Difference (MD) values and their 95% Confidence Intervals (CI) by both fixed and random effect models using Revman 5.4.1 software. Results: A total of six trials were found to be eligible and included in quantitative synthesis of efficacy. Small but significant decrease in total CARS score (MD: ?1.86, 95% CI: ?3.20, ?0.15, n = 352) and total social responsive scale score (MD: ?9.38, 95% CI: ?16.45, ?2.31, n = 171) on day 91 was evident in bumetanide treated group. Conclusions: Bumetanide appears to provide small but significant benefits in relieving ASD symptoms. These benefits are lesser in Chinese patients compared to European patients.
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Objective To investigate the effects of sevoflurane exposure on the hypothalamic-pituitary-adrenal (HPA)axis development in neonatal rats.Methods Fifty-four SD rats (P6)were randomly divided into three groups:control group (group C),sevoflurane group (group S)and bu-metanide+sevoflurane group (group BS),n = 18 in each group.In group C,rats were treated with pure oxygen for 6 hours and rats in group S received 2.1% sevoflurane anesthesia for 6 h.Rats in group BS also received 2.1% sevoflurane anesthesia for 6 h,but they were injected with bumetanide before 30 min and at 3 h during the anesthesia.6 rats from each group were randomly selected and the tail blood was collected to measure the corticosterone in the serum using ELISA.Remaining rats in each group were normally housed to P60.A elevated plus maze (EPM)were employed to investigate the anxiety-like behavior,and restraint stress were used to evaluate the function of HPA axis. Results In P6 rats,sevoflurane significantly increased the serum corticosterone level (P < 0.01 ) while bumetanide pretreatment decreased corticosterone level (P <0.01).In P60 rats,neonatal expo-sure to sevoflurane decreased the visits and time spent in the open arms of EPM (P < 0.05 ),in-creased the corticosterone level pre-stress and post-stress (P <0.05 or P < 0.01 ).Pretreatment of bumetanide normalized serum corticosterone level and the anxiety behavior in the EPM. Conclusion Neonatal sevoflurane exposure caused hyperactive HPA axis in rats,which is normalized by bumetanide pretreatment through blocking GABAA receptors.
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Objective To explore the application of bumetanide to inhibition of tumor cell proliferation.Methods In different cell lines, the expression of natrium,kalium, chloride cotransporter 1 ( NKCC1) was detected by Western blotting while the proliferation of different tumor cells was examined by CCK-8 kit.Results The target protein NKCC1 expression in lung cancer cell line ( A549 ) and colorectal cancer cell line ( HCT116 ) was significantly higher than that in chronic myelogenous leukemia cell line (K562), esophageal cancer cell line (Eca109), cervical carcinoma cell line (HeLa), T lymphocytic leukemia cell line (Jurkat) and breast cancer cell line (MCF7).IC50 Values of bumetanide were significantly lower in A549 and HCT116 than in K562, Eca109,HeLa,Jurkat and MCF7.Furthermore, the inhibiory rate and the target protein expression level were positively correlated.Conclusion Bumetanide can inhibit tumor cell proliferation and NKCC1 can serve as a potential target of anticancer drugs.
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Objective The purpose of this study was to observe the effects of bumetanide on elderly type 2 diabetic patients with middle and advanced stages nephropathy. Methods Forty cases with diabetic nephropathy (DN) were divided into two groups:control group (20 cases) and treatment group (20 cases) . The control group accepted furosemide (20 mg, once a day) and the bumetanide was orally administrated at the dose of 1.0 mg, twice a day to the treatment group for 3 months. The assessment of transferrin (TRF) and urine microalbumin (UALB) was performed at the time points at the end of 1, 4, 8, 12 weeks after treatment. Results (1) The levels of BUN, SCr and UA after treatment were lower than before treatment, but there were no significant differences. (2) In the treatment group, the levels of TRF and UALB have decreased after treatment for 1 week, with no statistically significant. But at the end of 4, 8 and 12 weeks,the differences were statistically significant ( <0.05) . Especially, during the three months follow-up,the levels of TRF and UALB at 12 weeks have decreased obviously. Conclusion The therapeutic effect of bumetanide on DN might be better than that of furosemide.
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Objective To investigate the effect of bumetanide pretreatment on focal cerebral ischemiareperfusion(I/R) injury in rats.Methods One hundred and five male SD rats weighing 250-300 g were randomly divided into 3 groups (n =35 each ):sham operation group(group S),focal cerebral I/R group (group I/R) and bumetanide pretreatment group (group B).Focal cerebral I/R was induced by occluding the fight middle cerebral artery with a nylon thread with a rounded tip which was inserted into internal carotid artery and advanced cranically until resistance was met in groups I/R and B.In group B bumetanide 30 mg/kg was injected iv at 10 min before ischemia.Neurologic function was assessed and scored-neurologic deficit scores (0 =no deficit,4 =unable to move).The animals were sacrificed at 3,24 and 48 h of reperfusion and their brains were immediately removed for determination of cerebral water content and expression of Na+ -K+ -2Cl- cotransporter 1 (NKCC1).The infarct size was measured at 24 h of reperfusion.Results Focal cerebral I/R significantly increased neurelogic deficit scores,NKCC1 expression,cerebral water content and infarct size in group I/R as compared with group S.Bumetanide pretreatment significantly attenuated cerebral focal I/R-induced increase in neurologic deficit scores,NKCC1 expression and cerebral water content in group B as compared with group I/R.There was no significant difference in infarct size between groups I/R and B.Conclusion Bumetanide pretreatment can reduce focal cerebral I/R injury in rats,and down-regulation of NKCC1 expression is involved in the mechanism.
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Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance.
Subject(s)
Animals , Male , Rats , Blood Glucose/analysis , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Epithelial Sodium Channels/analysis , Hypertension/complications , Immunoblotting , Immunohistochemistry , Kidney/metabolism , Sodium/metabolism , Sodium-Hydrogen Exchangers/genetics , Sodium-Potassium-Chloride Symporters/geneticsABSTRACT
OBJECTIVE:To establish a method for content determination of the principal agent in bumetanide tablets by HPLC-fluoremetry.METHODS:HPLC-fluoremetry was carried out using a Kromasil C 18 column and a mobile phase con?sisting of acetonitrile-water(50∶50),the fluorescence detector of228nm for excitation and418nm for emission was used,the internal standard was dixiben,the flow rate was0.6ml/min,the sample size was20?l,the column temperature was the same as room temperature.RESULTS:The concentration of bumetanide was linear in the range of16.75～335.00?g/ml(r=0.9997),the average recovery was99.26%(RSD=0.49%,n=3).CONCLUSION:The present method is convenient and reliable,whi_ ch can be used for content determination of the principal agent in bumetanide tablets.