RESUMO
BACKGROUND: Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders, including megaesophagus. Treatment focuses on improving symptoms, and isosorbide and nifedipine may be used for this purpose. METHODOLOGY: We conducted a systematic review to evaluate the effectiveness of pharmacological treatment for Chagas' megaesophagus. We searched MEDLINE, Embase and LILACS databases up to January 2018. We included both observational studies and RCTs evaluating the effects of isosorbide or nifedipine in adult patients with Chagas' megaesophagus. Two reviewers screened titles and abstracts, selected eligible studies and extracted data. We assessed the risk of bias using NIH 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group' and RoB 2.0 tool. Overall quality of evidence was assessed using GRADE. PRINCIPAL FINDINGS: We included eight studies (four crossover RCTs, four before-after studies). Three studies evaluated the effect of isosorbide on lower esophageal sphincter pressure (LESP), showing a significant reduction (mean difference -10.52mmHg, 95%CI -13.57 to-7.47, very low quality of evidence). Three studies reported the effect of isosorbide on esophageal emptying, showing a decrease in esophageal retention rates (mean difference -22.16%, 95%CI -29.94 to -14.38, low quality of evidence). In one study, patients on isosorbide reported improvement in the frequency and severity of dysphagia (moderate quality of evidence). Studies evaluating nifedipine observed a decrease in LESP but no effect on esophageal emptying (very low and low quality of evidence, respectively). Isosorbide had a higher incidence of headache as a side effect than nifedipine. CONCLUSIONS: Although limited, available evidence shows that both isosorbide and nifedipine are effective in reducing esophageal symptoms. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile. TRIAL REGISTRATION: PROSPERO CRD42017055143. ClinicalTrials.gov CRD42017055143.
Assuntos
Doença de Chagas/complicações , Acalasia Esofágica/tratamento farmacológico , Isossorbida/administração & dosagem , Nifedipino/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemAssuntos
Humanos , Masculino , Feminino , Pressão Venosa/efeitos dos fármacos , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/prevenção & controle , Politetrafluoretileno/uso terapêutico , Propranolol/uso terapêutico , Recidiva , Varizes Esofágicas e Gástricas/etiologia , Stents , Reprodutibilidade dos Testes , Medicina Baseada em Evidências , Quimioterapia Combinada , Hemorragia Gastrointestinal/etiologia , Isossorbida/uso terapêutico , Cirrose Hepática/complicaçõesRESUMO
Hepatitis C infection is a cause of chronic liver diseases such as cirrhosis and carcinoma. The current therapy for hepatitis C has limited efficacy and low tolerance. The HCV encodes a serine protease which is critical for viral replication, and few protease inhibitors are currently on the market. In this paper, we describe the synthesis and screening of novel isosorbide-based peptidomimetic inhibitors, in which the compounds 1d, 1e, and 1i showed significant inhibition of the protease activity in vitro at 100µM. The compound 1e also showed dose-response (IC50=36±3µM) and inhibited the protease mutants D168A and V170A at 100µM, indicating it as a promising inhibitor of the HCV NS3/4A protease. Our molecular modeling studies suggest that the activity of 1e is associated with a change in the interactions of S2 and S4 subsites, since that the increased flexibility favors a decrease in activity against D168A, whereas the appearance of a hydrophobic cavity in the S4 subsite increase the inhibition against V170A strain.
Assuntos
Antivirais/química , Hepacivirus/enzimologia , Isossorbida/química , Serina Proteases/química , Inibidores de Serina Proteinase/química , Antivirais/síntese química , Antivirais/farmacologia , Sítios de Ligação , Domínio Catalítico , Hepacivirus/efeitos dos fármacos , Isossorbida/síntese química , Isossorbida/farmacologia , Simulação de Acoplamento Molecular , Mutação , Peptidomiméticos , Serina Proteases/genética , Serina Proteases/metabolismo , Inibidores de Serina Proteinase/síntese química , Inibidores de Serina Proteinase/farmacologia , Termodinâmica , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismoAssuntos
Angina Pectoris Variante/diagnóstico por imagem , Vasoespasmo Coronário/diagnóstico por imagem , Angina Pectoris Variante/tratamento farmacológico , Angina Pectoris Variante/fisiopatologia , Angiografia , Cálcio/agonistas , Vasoespasmo Coronário/fisiopatologia , Diagnóstico Diferencial , Humanos , Isossorbida/uso terapêutico , Masculino , Pessoa de Meia-IdadeAssuntos
Humanos , Masculino , Pessoa de Meia-Idade , Vasoespasmo Coronário/diagnóstico por imagem , Angina Pectoris Variante/diagnóstico por imagem , Angiografia , Cálcio/agonistas , Vasoespasmo Coronário/fisiopatologia , Diagnóstico Diferencial , Isossorbida/uso terapêutico , Angina Pectoris Variante/fisiopatologia , Angina Pectoris Variante/tratamento farmacológicoRESUMO
INTRODUÇÃO: Fissuras anais crônicas são úlceras benignas, dolorosas, profundas. Ocorrem devido a trauma das fezes, hipertonia esfincteriana e pobre vascularização. Cirurgia é mais efetiva, porém com efeitos adversos (incontinência anal). Terapia conservadora consegue decréscimo transitório da pressão de repouso, cicatrizando muitas lesões, sem dano muscular. MÉTODOS: Objetivando avaliar tratamento de fissuras crônicas com isossorbida (ISO) a 1 por cento tópica, foi realizado um ensaio clínico, duplo-cego em pacientes do Serviço de Coloproctologia da Universidade Federal de Sergipe (UFS) - Aracaju, Sergipe, durante um ano. Foram estudados 24 pacientes: 14 no Grupo 1 - creme com ISO, e 10 no Grupo 2 - placebo. Avaliaram-se comportamento da pressão de repouso, melhora da dor e grau de cicatrização das feridas com e sem ISO. RESULTADOS: Resultados mostraram que a fissura acometeu mais mulheres, a constipação foi observada em 58,3 por cento. Quanto à dor, obteve-se menor intensidade no Grupo 2, mas sem significância. A cicatrização ao fim de 60 dias foi igual nos dois grupos (50 por cento). Quanto às médias de pressão de repouso com 30 e 60 dias, houve queda no padrão em ambos os grupos, porém sem significância. Observou-se que pacientes curados foram os de maior redução de pressão de repouso. CONCLUSÃO: Concluiu-se que a ISO não modificou o padrão de resposta manométrica; todavia, houve melhora clínica importante nos dois grupos, cuja taxa de cicatrização foi equivalente.
INTRODUCTION: Chronic anal fissures are deep, benign and painful ulcers. The involved factors are local trauma, sphinter hypertonia and poor blood flow. Surgery is gold standard treatment, but it causes fecal incontinence. Medical non-surgical therapy gets transitory resting pressure reduction and cure of lesions, without muscular damage. METHODS: In order to evaluate the treatment of chronic anal fissures using topical isossorbide (ISO) 1 percent, a randomizated and double-blind study twas carried out in Coloproctology Section of Universidade Federal de Sergipe (UFS), Sergipe, Brazil, during one year. Twenty-four patients were evaluated: 14 in Group 1 - ISO cream, and 10 in Group 2 - placebo. Resting pressure profile, improvement of painful symptoms and degree of scaring of the fissure were evaluated. RESULTS: Ulcer was more prevalent in women, constipation was present in 58.3 percent. The evacuatory pain was less common in Group 2, but without statistical significance. After 60 days, the healing was equal in the both groups (50 percent). There was a small reduction of resting pressure means at the end of 30 and 60 days, without statistical significance. Healing patients presented more resting pressure reducing. CONCLUSION: ISO cream did not influence the manometric response standard; otherwise it offered clinical improvement in both groups, whose scarring index was similar.
Assuntos
Humanos , Masculino , Feminino , Adulto , Fissura Anal , Isossorbida , ManometriaRESUMO
BACKGROUND: Continuous infusion of short life vasodilators are employed to test reversibility of pulmonary hypertension in cardiac transplant candidates. Sublingual isosorbide administration has not been described in the literature and it might be a simpler alternative. AIM: To evaluate sublingual isosorbide administration as a test of reversibility of pulmonary hypertension in heart failure. PATIENTS AND METHODS: Prospective evaluation of patients referred for cardiac transplant evaluation. Patients underwent right catheterization for hemodynamic measurements at baseline and after repeated doses of 5 mg sublingual isosorbide every 5 minutes until observing a decrease in pulmonary vascular resistance decrease or symptomatic hypotension. RESULTS: Twenty one patients, 18 men, age 49+/-15 years, were studied. Fourteen (66%) were transplanted. The mean sublingual isosorbide dose was 15+/-5 mg. After isosorbide administration, there was a significant decrease in mean arterial pressure (80+/-8.5 to 71+/-6.6 mmHg, p <0.0001), mean pulmonary artery pressure (38+/-11 to 26+/-7.8 mmHg, p <0.0001), systemic vascular resistance (1540+/-376 to 1277+/-332 dyn*s/cm5 p <0.001), pulmonary vascular resistance (3.5+/-2.2 to 2,5+/-1.6 Wood Units, p <0.05) and transpulmonary gradient (13+/-7 a 10+/-4 mmHg, p <0.004). The cardiac output increased from 3.96+/-0.7 to 4.38+/-0.9 L/min, p=0.05. The relation between pulmonary and systemic vascular resistance before and after isosorbide was 0.17 and 0.15, respectively (p=0.04). One transplanted patient with partial reversibility of pulmonary hypertension developed acute right heart failure. CONCLUSIONS: Sublingual isosorbide administration is useful and well tolerated to evaluate the reversibility of pulmonary hypertension prior cardiac transplant.
Assuntos
Baixo Débito Cardíaco/cirurgia , Diuréticos Osmóticos/administração & dosagem , Transplante de Coração , Hipertensão Pulmonar/tratamento farmacológico , Isossorbida/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Sublingual , Cateterismo Cardíaco , Baixo Débito Cardíaco/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Background: Continuous infusion of short life vasodilators are employed to test reversibility of pulmonary hypertension in cardiac transplant candidates. Sublingual isosorbide administration has not been described in the literature and it might be a simpler alternative. Aim: To evaluate sublingual isosorbide administration as a test of reversibility of pulmonary hypertension in heart failure. Patients and Methods: Prospective evaluation of patients referred for cardiac transplant evaluation. Patients underwent right catheterization for hemodynamic measurements at baseline and after repeated doses of 5 mg sublingual isosorbide every 5 minutes until observing a decrease in pulmonary vascular resistance decrease or symptomatic hypotension. Results: Twenty one patients, 18 men, age 49±15 years, were studied. Fourteen (66%) were transplanted. The mean sublingual isosorbide dose was 15±5 mg. After isosorbide administration, there was a significant decrease in mean arterial pressure (80±8.5 to 71±6.6 mmHg, p <0.0001), mean pulmonary artery pressure (38±11 to 26±7.8 mmHg, p <0.0001), systemic vascular resistance (1540±376 to 1277±332 dyn*s/cm5 p <0.001), pulmonary vascular resistance (3.5±2.2 to 2,5±1.6 Wood Units, p <0.05) and transpulmonary gradient (13±7 a 10±4 mmHg, p <0.004). The cardiac output increased from 3.96±0.7 to 4.38±0.9 L/min, p=0.05. The relation between pulmonary and systemic vascular resistance before and after isosorbide was 0.17 and 0.15, respectively (p=0.04). One transplanted patient with partial reversibility of pulmonary hypertension developed acute right heart failure. Conclusions: Sublingual isosorbide administration is useful and well tolerated to evaluate the reversibility of pulmonary hypertension prior cardiac transplant.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Baixo Débito Cardíaco/cirurgia , Diuréticos Osmóticos/administração & dosagem , Transplante de Coração , Hipertensão Pulmonar/tratamento farmacológico , Isossorbida/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Sublingual , Baixo Débito Cardíaco/etiologia , Cateterismo Cardíaco , Estudos ProspectivosRESUMO
BACKGROUND: The role of nitric oxide (NO) on bone metabolism is controversial, since it can either stimulate bone formation or resorption. We investigated the effect of local administration of the NO donor isosorbide in an experimental periodontal disease model. METHODS: Wistar rats were subjected to a ligature placement around the cervix of the right second upper molar and were sacrificed after 11 days. Alveolar bone loss was measured in one quadrant as the sum of the distances between the cuspid tip and the alveolar bone along the axis of each molar root, which was subtracted from the contralateral side, used as unligated control. The semiquantitative histopathological scale of the periodontium was based on cell infiltration and alveolar bone and cementum integrity. Groups were treated with a gel containing 1% or 5% isosorbide applied to the vestibular side of the molar gingiva 1 hour before the placement of the ligature and then twice daily until sacrifice. Controls included one group subjected to periodontitis and no treatment (NT) and another that received the gel containing just the vehicle (V). RESULTS: The application of the vehicle gel produced an increase of the alveolar bone resorption, without altering the inflammatory changes, compared to the NT group. The 5% isosorbide produced a significant reduction of the alveolar bone resorption, compared to V and NT. This reduction was confirmed by histological analysis, showing less inflammatory cell infiltration and preservation of the cementum and the alveolar process. CONCLUSION: Local application of isosorbide reduces alveolar bone resorption in experimental periodontal disease in rats, suggesting a local anti-inflammatory effect of isosorbide.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Isossorbida/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Periodontite/prevenção & controle , Perda do Osso Alveolar/patologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologia , Animais , Cemento Dentário/efeitos dos fármacos , Cemento Dentário/patologia , Dentina/efeitos dos fármacos , Dentina/patologia , Modelos Animais de Doenças , Gengiva/efeitos dos fármacos , Gengiva/patologia , Dente Molar/patologia , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/patologia , Veículos Farmacêuticos , Ratos , Ratos WistarRESUMO
OBJECTIVE: To evaluate the impact of the use, prior to the procedure, of injectable diltiazem to prevent complications. METHODS: Between September 2000 and July 2001, 50 patients underwent transradial coronary angiography and were randomized to receive placebo (GI) or diltiazem (GII) through a catheter inserted into the radial artery. All patients received isosorbide mononitrate. Ultrasound analyses of the radial artery were performed before examination, 30 minutes afterwards, and 7 days afterwards to evaluate the flow, the diameter, and the artery output. RESULTS: The radial artery diameter of GI was 2.4d +/- 0.5 mm before the procedure and 2.3 +/- 0.5 mm after 30 minutes (NS), whereas in GII the diameter was 2.2 +/- 0.3 mm before the examination and +/- 2.5 0.4 mm 30 minutes after it (P<0.001). Radial artery output in group 1 was 7.3 +/- 5.l2 mL/min before the examination and 6.1 +/- 3.5 mL/min 30 minutes after the examination (NS), and GII had an increase of 5.9 +/- 2.5 mL/min before examination to 9.05 +/- 7.78 mL/min after the examination (P=0.04). Complications (spasm, occlusion, and partial obstruction) occurred in 4 patients (17.4%) in GI and did not occur in GII (P=0.04). CONCLUSION: The study suggests a decrease in vascular complications through the transradial access for coronary angiography with the use of diltiazem as an antispasmodic drug, resulting in the significant increase in the diameter of the radial artery and radial artery output.