RESUMO
Insulinoma is a rare neuroendocrine tumor originating from hypersecreting beta-cells of islets of Langerhans in the pancreas. We report a case of 72-year-old male, with chronic alcohol abuse, presenting with atypical features like refractory recurrent secondary generalized seizures and behavioral disturbances with increased irritability, initially mistreated as alcohol withdrawal. Detailed history, particularly the relationship of the symptoms with food intake, made us think of other causes of seizures. Fasting biochemical investigations and localizing studies helped clinch the diagnosis. The tumor was localized with the help of endoscopic ultrasonography and whole-body Ga68-DOTANOC PET-CT. The patient was treated conservatively with diazoxide and is doing well on follow-up. The present case report emphasizes the importance of detailed clinical history, more so in atypically presenting cases of refractory seizures. Insulinoma can be medically managed despite surgery being the gold standard curative treatment.
Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diazóxido/uso terapêutico , Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Idoso , Alcoolismo , Complicações do Diabetes , Diabetes Mellitus Tipo 2/sangue , Endossonografia , Humanos , Insulinoma/patologia , Insulinoma/cirurgia , Masculino , Compostos Organometálicos/metabolismo , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Cintilografia , Convulsões/etiologia , Imagem Corporal TotalRESUMO
An efficient one-pot iodination methodology for the synthesis of benzothiazolo-4ß-anilino-podophyllotoxin (5a-h) and benzothiazolo-4ß-anilino-4-O-demethylepipodophyllotoxin (6a-h) congeners has been successfully developed by using zirconium tetrachloride/sodium iodide. Interestingly, this protocol demonstrates enhancement of stereoselectivity apart from the improvement in the yields in comparison to previous methods reported for such related podophyllotoxin derivatives. These compounds have been designed and synthesized using association strategy by coupling of 4ß-podophyllotoxin and 4ß-demethylepipodophyllotoxin with a variety of substituted aminoaryl benzothiazoles. Some of the representative compounds have been evaluated for their cytotoxicity against selected human cancer cell lines and DNA topoisomerase-II inhibition activity.
Assuntos
Antineoplásicos/síntese química , Benzotiazóis/química , DNA Topoisomerases Tipo II/química , Podofilotoxina/química , Inibidores da Topoisomerase II/síntese química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Cloretos/química , DNA Topoisomerases Tipo II/metabolismo , Halogenação , Humanos , Neoplasias/tratamento farmacológico , Podofilotoxina/uso terapêutico , Podofilotoxina/toxicidade , Inibidores da Topoisomerase II/uso terapêutico , Inibidores da Topoisomerase II/toxicidade , Zircônio/químicaRESUMO
Pyrrolobenzodiazepine-diethylphosphonate conjugates have been designed and synthesized that link through two different types of spacers that are simple alkane chain and also a piperazine moiety side-armed with the alkane chains. These pyrrolobenzodiazepine conjugates have exhibited remarkable DNA-binding affinity and improved solubility in water, a representative compound 7d showing promising in vitro cytotoxicity.
Assuntos
Benzodiazepinas/síntese química , Benzodiazepinas/toxicidade , DNA/química , Organofosfonatos/química , Pirróis/síntese química , Pirróis/toxicidade , Aminação , Animais , Benzodiazepinas/química , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dimerização , Humanos , Estrutura Molecular , Desnaturação de Ácido Nucleico , Pirróis/química , Relação Estrutura-Atividade , TemperaturaRESUMO
A new versatile acrylonitrile-bioconverting strain isolated from a petroleum-contaminated sludge sample and identified as Rhodococcus ruber AKSH-84 was used for optimization of medium and biotransformation conditions for nitrilase activity to produce acrylic acid. A simple and rapid HPLC protocol was optimized for quantification of acrylic acid, acrylamide, and acrylonitrile. The optimal medium conditions for nitrilase activity were pH of 7.0, temperature of 30degreesC, agitation of 150 rpm, and inoculum level of 2%. Glycerol as a carbon source and sodium nitrate as the nitrogen source provided good nutritional sources for achieving good biotransformation. Nitrilase activity was constitutive in nature and was in the exponential growth phase after 24 h of incubation under optimal conditions without addition of any inducer. The substrate preference was acrylonitrile and acetonitrile. The present work demonstrates the biotransformation of acrylonitrile to acrylic acid with the new strain, R. ruber AKSH-84, which can be used in green biosynthesis of acrylic acid for biotechnological processes. The nitrilase produced by the isolate was purified and characterized.
Assuntos
Acrilatos/metabolismo , Acrilonitrila/metabolismo , Rhodococcus/metabolismo , Aminoidrolases/química , Aminoidrolases/genética , Aminoidrolases/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biotransformação , Estabilidade Enzimática , Dados de Sequência Molecular , Rhodococcus/enzimologia , Rhodococcus/genética , Rhodococcus/isolamento & purificação , Esgotos/microbiologia , Especificidade por SubstratoRESUMO
The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 +/- 2.85 mu g/cm(2.)h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.
Assuntos
Antieméticos/farmacocinética , Excipientes/química , Ondansetron/farmacocinética , Administração Cutânea , Animais , Celulose/análogos & derivados , Celulose/química , Epiderme/metabolismo , Etanol/química , Masculino , Mentol/química , Permeabilidade , Ratos , Absorção Cutânea , Solventes/química , Água/químicaRESUMO
Benzothiadiazine-pyrrolobenzodiazepine conjugates linked through different alkane spacers have been prepared. These new classes of hybrid molecules exhibit cytotoxicity against many cancer cell lines. Their DNA thermal denaturation studies have been carried out and one of the compounds (4b) elevates the DNA helix melting temperature of the CT-DNA by 6.7 degrees C after incubation for 36 h.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Benzodiazepinas/síntese química , Benzodiazepinas/metabolismo , Benzotiadiazinas/síntese química , Benzotiadiazinas/metabolismo , DNA/metabolismo , Animais , Antineoplásicos/farmacologia , Benzodiazepinas/farmacologia , Benzotiadiazinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Bovinos , Linhagem Celular Tumoral , Enzimas de Restrição do DNA/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Indicadores e Reagentes , Masculino , Desnaturação de Ácido Nucleico/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Relação Estrutura-AtividadeRESUMO
Fluoroquinolones have been synthesized and linked to DC-81 at C8 position through different alkyl chain spacers. These PBD conjugates have exhibited good DNA binding affinity, and a representative compound shows promising in vitro anticancer activity.
Assuntos
Benzodiazepinas/síntese química , Benzodiazepinas/farmacologia , Fluoroquinolonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Benzodiazepinas/química , Benzodiazepinas/metabolismo , Bovinos , Linhagem Celular Tumoral , DNA/metabolismo , Dimerização , Endonucleases/antagonistas & inibidores , Endonucleases/metabolismo , Fluoroquinolonas/síntese química , Fluoroquinolonas/química , Fluoroquinolonas/metabolismo , Humanos , Estrutura Molecular , Naftiridinas/química , TemperaturaRESUMO
Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines via azido reductive cyclization process employing FeCl3-NaI reagent system. This methodology has been extended for the preparation of new nicotinamido-pyrrolobenzodiazepine hybrids linked through piperazino-alkane-oxy spacers that exhibit good DNA binding affinity.
Assuntos
Azidas/química , Benzodiazepinas/síntese química , DNA/metabolismo , Benzodiazepinas/química , Benzodiazepinas/metabolismo , Eletroforese em Gel de ÁgarRESUMO
The synthesis of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers is reported and these dimers show significant DNA binding affinity and they also exhibit moderate anticancer activity.