RESUMO
The overall expectation from an antimicrobial surface has been high considering the need for efficiency in preventing the attachment and growth of pathogenic microbes, durability, safety to both humans and environment as well as cost-effectiveness. To date, antimicrobial surface design has been mostly conducted liberally, without rigorous consideration of establishing robust structure-activity relationships for each design strategy or of the use intended for a specific antimicrobial material. However, the variability among the domain bacteria, which is the most diverse of all, alongside the highly dynamic nature of the bacteria-surface interface have taught us that the likelihood of finding universal antimicrobial surfaces is low. In this perspective we discuss some of the current hurdles faced by research in this promising field, emphasizing the relevance and complexity of probing the bacteria-surface interface, and explain why we feel it would greatly benefit from a more streamlined ad-hoc approach.
RESUMO
It is almost 70 years since the discovery by Huggins et al. that androgens are essential for prostate cancer (PC) growth and progression, and there has been about 30 years experience using ketoconazole for PC therapy. Since then we have come a long way in learning about the disease and developing new strategies to approach it, among which is cytochrome 17alpha-hydroxylase-C(17,20)-lyase (CYP17) inhibition. This review focuses on the efforts to find prospective CYP17 inhibitors, both steroidal and nonsteroidal, in the absence of a 3D structure of the enzyme. It covers almost 4 decades of literature with highlights on the most significant achievements in this area, providing insight into PC pathophysiology, management and treatment options.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Androgênios/química , Androgênios/metabolismo , Androstanos/química , Androstanos/metabolismo , Androstanos/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Humanos , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/uso terapêutico , Masculino , Pregnanos/química , Pregnanos/metabolismo , Pregnanos/uso terapêutico , Neoplasias da Próstata/enzimologia , Piridinas/química , Piridinas/metabolismo , Piridinas/uso terapêutico , Esteroide 17-alfa-Hidroxilase/metabolismoRESUMO
To characterize the convulsions induced by a hexanic extract of Spilanthes acmella var. oleracea, male Wistar rats were injected ip with 50 to 150 mg/kg of the extract and EEG and behavior were observed for periods as long as 2 h. Following the lower doses (50 and 75 mg/kg) only minor behavioral changes such as grooming and wet dog shakes were observed. Higher doses (100 to 150 mg/kg) induced full tonic-clonic convulsions in a dose-dependent manner which were accompanied by typical electrographic seizures in the EEG. These results confirm that the hexane extract of Spilanthes acmella var. oleracea is able to induce generalized convulsions in rats and can be used as a tool in the development of new models of epilepsy.
Assuntos
Comportamento Animal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Convulsões/induzido quimicamente , Animais , Brasil , Eletroencefalografia , Masculino , Plantas Medicinais , Ratos , Ratos EndogâmicosRESUMO
To characterize the convulsions induced by a hexanic extract of Spilanthes acmella var. oleracea, male Wistar rats were injected ip with 50 to 150 mg/kg of the extract and EEG and hehavior were observed for periods as long as 2 h. Following the lower doses (50 and 75 mg/kg) only minor behavioral changes such as grooming and wet dog shakes were observed. Higher doses (100 to 150 mg/kg) induced full tonic-clonic convulsions in a dose-dependent manner which were accompanied by typical electrographic seizures in the EEG. These results confirm that the hexane extract of Spilanthes acmella var. oleracea is able to induce generalized convulsions in rats and can be used as a tool in the development of new models of epilepsy