RESUMO
INTRODUCTION: Despite the number of deaths and the significant economic and social costs associated with Chagas, Leishmaniasis and Malaria diseases worldwide, available drugs are limited and have serious side effects and high toxicity for the patient. Therefore, there is an urgent need for safe, low-cost, and effective treatments. Natural products are an important source of bioactive compounds and there is current interest in finding natural bioactive molecules that can be used for treating these parasitic diseases. In the present study we proposed to evaluate the in vitro antiparasitic activity of new menthol derivatives against Trypanosoma cruzi, Leishmania braziliensis and Plasmodium falciparum; moreover, we propose to explore their mode of action through in silico approaches. MATERIAL AND METHODS: A series of carbonate prodrugs (1-9) were synthesized from menthol with different aliphatic alcohols. Spectroscopic techniques were used to confirm the structures of the synthesized compounds. The cytotoxicity of the compounds was assessed using U-937 cells. In vitro trypanocidal, leishmanicidal and antiplasmodial activity were evaluated using a T. cruzi, L. braziliensis and P. falciparum organism, respectively. In addition, in silico studies were also performed through molecular dynamics simulations and MM-PBSA analysis. RESULTS: The assay revealed that most of the compounds were highly active against intracellular amastigotes of T. cruzi and L. braziliensis, and had moderate activity against the total forms of P. falciparum. Compound 2 was one of the drugs that showed a high selectivity index (SI) for the three organisms evaluated. The prediction of the ADME properties suggests that all the compounds have drug-like molecular properties and the probability to be lead candidates. Finally, molecular dynamics simulations, and MM-PBSA studies indicate that menthol at the substrate binding site of TcDHODH, LbDHODH and PfDHODH is structurally stable in the same order as the natural substrate; also, interactions of menthol with residues involved in the inhibition of TcDHODH and PfDHODH proteins were predicted. CONCLUSIONS: The present study demonstrates that menthol prodrugs are promising antiparasitic agents; however, the mechanisms of action proposed in this study need to be experimentally verified by future enzymatic assays.
Assuntos
Doença de Chagas , Pró-Fármacos , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Carbonatos/uso terapêutico , Doença de Chagas/tratamento farmacológico , Computadores , Humanos , Mentol/farmacologia , Pró-Fármacos/uso terapêuticoRESUMO
The aim of this study was to evaluate the impact of group psychotherapy and the use of a phosphodiesterase-5 inhibitor (PDE-5i) in the early rehabilitation stage of patients with prostate cancer undergoing radical prostatectomy (RP). Fifty-six patients undergoing RP for prostate cancer were randomised into four groups, and 53 completed the protocol: Group 1 - control (n = 11), Group 2 - group psychotherapy (n = 16), Group 3 - lodenafil 80 mg/one tablet per week (n = 12) and Group 4 - group psychotherapy + lodenafil 80 mg/one tablet per week (n = 14). The groups were individually evaluated for erectile function (IIEF-5) and quality of life - QoL (SF-36) weekly, with two meetings held a week apart before the RP and 12 weekly meetings after surgery. The ages ranged from 39 to 76 years, average 61.84. There were no significant medication side effects. Only Group 4 showed improvement in intimacy with a partner and satisfaction with their sex life (P = 0.045 and P = 0.013 respectively), and with no significant worsening of the IIEF-5 (P = 0.250) reported. All groups showed worsening in the final result of the role limitations caused by physical problems (P = 0.009) and role limitations caused by emotional problems (P = 0.002) of the SF-36, but Group 4 had a significantly higher score for the role limitations caused by physical problems (P = 0.009) than the other groups. In conclusion, precocious integral treatment involving group psychotherapy and PDE-5i before and after RP led to less deterioration of erectile function and other domains related to physical aspects (SF-36), with improvement in intimacy with their partner and satisfaction in their sex life, being superior to single treatments.
Assuntos
Carbonatos/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Ereção Peniana/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/uso terapêutico , Piperazinas/uso terapêutico , Prostatectomia/efeitos adversos , Psicoterapia , Pirimidinas/uso terapêutico , Qualidade de Vida/psicologia , Adulto , Idoso , Carbonatos/farmacologia , Terapia Combinada , Disfunção Erétil/etiologia , Disfunção Erétil/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/psicologia , Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Estudos Prospectivos , Prostatectomia/psicologia , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/cirurgia , Pirimidinas/farmacologia , Resultado do TratamentoRESUMO
We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.
Assuntos
Carbonatos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Animais , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Masculino , Monocrotalina , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: To assess persistence/adherence rates of phosphodiesterase type-5 inhibitor (PDE5I) on-demand dosing in Latin American men with erectile dysfunction (ED), and explore patient characteristics and treatment factors that may be predictive for PDE5I persistence and adherence. METHODS: Men from Brazil, Mexico, and Venezuela with ED who were naïve to PDE5Is were prescribed sildenafil, tadalafil, vardenafil, or lodenafil on-demand dosing and asked to provide information about PDE5I use at baseline and at 1, 3, and 6 months. Patients were persistent if they used ≥1 dose during the 4 week period prior to each evaluation. Patients were adherent if they complied with dosing instructions during most recent dose. Main outcome measures included Persistence and Adherence Questionnaire (PAQ), Partner Relationship Questionnaire (PRQ), Self-Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence and adherence. RESULTS: A total of 511 men were enrolled; most had mild to moderate ED (77.1%); 317 patients (62.0%) were prescribed tadalafil, 116 (22.7%) sildenafil, 75 (14.7%) vardenafil, and 3 (0.6%) lodenafil (not further analyzed). A total of 340 patients (66.5%) were 'persistent' at 6 months; 345 (67.5%) were 'adherent'. Persistence and adherence were associated with age, education level, and ED duration. Reasons for non-persistence included medication cost and lack of efficacy. Study limitations included its design, brief observation period, its bias observed toward tadalafil selection; its dependence on patient self-reporting, limited number of factors that were analyzed for persistence/adherence association, its small number of participating patients and Latin American countries, and inherent differences in PDE5I preference and medical practices. CONCLUSION: Approximately two-thirds of PDE5I-naïve, Latin American men with ED were persistent and adherent after 6 months of therapy. Factors like education level, ED severity, and ED duration were associated with persistence and adherence; additional study is warranted to investigate the predictive value of these factors.
Assuntos
Disfunção Erétil/tratamento farmacológico , Adesão à Medicação , Inibidores da Fosfodiesterase 5/uso terapêutico , Carbolinas/uso terapêutico , Carbonatos/uso terapêutico , Humanos , Imidazóis/uso terapêutico , América Latina , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Estudos Prospectivos , Purinas/uso terapêutico , Pirimidinas/uso terapêutico , Autoimagem , Citrato de Sildenafila , Sulfonas/uso terapêutico , Inquéritos e Questionários , Tadalafila , Resultado do Tratamento , Triazinas/uso terapêutico , Dicloridrato de VardenafilaRESUMO
INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary.
Assuntos
Carbonatos/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Esquizofrenia/complicações , Adulto , Assistência Ambulatorial , Análise de Variância , Estudos Cross-Over , Método Duplo-Cego , Disfunção Erétil/complicações , Estradiol/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Prolactina/sangue , Qualidade de Vida , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangueRESUMO
INTRODUCTION: This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. AIM: Expanding information on LC efficacy and safety. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). METHODS: A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. RESULTS: IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] +/- standard deviation [SD]): placebo = 13.9 +/- 5.2 and 14.8 +/- 7.8; LC 40 mg = 13.6 +/- 5.3 and 18.6 +/- 8.0; LC 80 mg = 13.4 +/- 4.9 and 20.6 +/- 7.7 (analysis of variance [ANOVA] P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M +/- SD): placebo = 55.3 +/- 43.2% and 52.1 +/- 41.4%; LC 40 mg = 46.4 +/- 44.3% and 63.5 +/- 42.0%; LC 80 mg = 50.2 +/- 40.9% and 80.8 +/- 32.3% (ANOVA P < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 +/- 32.3% and 29.7 +/- 38.1%; LC 40 mg = 19.6 +/- 34.3% and 50.8 +/- 44.4%; LC 80 mg = 20.8 +/- 33.2% and 66.0 +/- 39.3% (ANOVA P < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. CONCLUSIONS: LC showed a satisfactory efficacy-safety profile for oral therapy of ED.
Assuntos
Inibidores da Fosfodiesterase 5 , Inibidores de Fosfodiesterase/uso terapêutico , Idoso , Carbonatos/efeitos adversos , Carbonatos/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Ereção Peniana/efeitos dos fármacos , Inibidores de Fosfodiesterase/efeitos adversos , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Estudos Prospectivos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. AIM: This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. MAIN OUTCOME MEASURES: Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. METHODS: Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. RESULTS: IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (ANOVA P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). CONCLUSIONS: The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated.
Assuntos
Carbonatos/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Administração Oral , Adulto , Idoso , Carbonatos/farmacologia , Método Duplo-Cego , Esquema de Medicação , Tolerância a Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5 , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Estudos Prospectivos , Pirimidinas/farmacologiaRESUMO
Abdominal wall wound dehiscences, more frequently those involving skin and subcutaneous tissue, are a common surgical complication in Obstetrics and Gynecology. A prospective, longitudinal study was done in 65 patients presenting with wound abscess. The evolution of the wound was compared using the following methods a) Bandage, b) Bandage with 30% iron subcarbonate pomade, c) Silk, d) Silk with 30% iron subcarbonate pomade. Eighty five percent of the patients, with silk used, were completely recovered in less than 10 days; comparing this option with the others used in this study, there were significant statistical differences.
Assuntos
Abscesso/etiologia , Cesárea/efeitos adversos , Deiscência da Ferida Operatória/etiologia , Músculos Abdominais , Abscesso/terapia , Adulto , Bandagens , Carbonatos/uso terapêutico , Feminino , Humanos , Ferro , Pomadas/administração & dosagem , Complicações Pós-Operatórias , Gravidez , Deiscência da Ferida Operatória/terapiaRESUMO
Se realizó un estudio retrospectivo de los pacientes hipertiroideos que requirieron tratamiento quirúrgico durante el período comprendido entre 1983 y 1987 en el Hospital Clinicoquirúrgico "Hermanos Ameijeiras". Se analizaron los 3 pacientes en que fue utilizado el carbonato de litio como modalidad terapéutica preoperatoria. Se señalaron las indicaciones, dosis efectos colaterales y contraindicaciones del medicamento
Assuntos
Humanos , Feminino , Carbonatos/uso terapêutico , Hipertireoidismo/tratamento farmacológico , Estudos Retrospectivos , Lítio/administração & dosagem , Lítio/uso terapêuticoRESUMO
En relación al aumento mantenido del consumo de carbonato de litio en el Hospital Psiquiátrico de Santiago observado desde el año 1986, se realizó un estudio farmacocinético de una formulación en cápsulas de carbonato de litio de 300 mg. en tres voluntarios sanos. Este estudio concluyó que la formulación en cápsulas presenta un comportamiento farmacocinético similar al de los comprimidos de 300 mg. elaborados por un laboratorio nacional. Basados en el estudio antes mencionado, se realizó un estudio clínico de 28 días de duración, en el que 13 pacientes (12 con el diagnóstico de Enfermedad Afectiva Bipolar y uno con el diagnóstico de Esquizofrenia) fueron tratados con carbonato de litio en cápsulas, en dosis entre 900 y 1800 mgrs./día y litemias promedio entre 0.6 y 0.9 m.Eq Lt. Un paciente bipolar fue tratado con comprimidos de carbonato de litio. de acuerdo a la evaluación con la escala de manía y depresión de Bech-Rafaelsen realizado los días 0 y 28 del estudio, los pacientes en fase maníaca mejoraron de manera estadísticamente significativa (P<0.0005), y los pacientes depresivos de la misma manera con un (P<0.025). Dos pacientes fueron marginados del estudio por no cumplir con el calendario de litemias. Doce pacientes han completado un período de observación de un año en el policlínico de Enfermedades Afectivas del Hospital Psiquiátrico sin que hayan presentado recaídas, siendo tratados en forma profiláctica con la formulación en cápsulas. En consecuencia, los resultados obtenidos del estudio farmacocinético y clínico nos permiten recomendar el uso de carbonato de litio en cápsulas de 300 mg