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1.
Biol. Res ; 47: 1-7, 2014. ilus, graf
Artículo en Inglés | LILACS | ID: biblio-950735

RESUMEN

BACKGROUND: Novel, in silico-designed anticancer compounds were synthesized in our laboratory namely, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). These compounds were designed to have improved bioavailability when compared to their source compound, 2-methoxyestradiol. This theoretically would be due to their increased binding affinity to carbonic anhydrase II, present in erythrocytes. Since the novel compounds under investigation are proposed to be transported within erythrocytes bound to carbonic anhydrase II, the morphological effect which they may exert on whole blood and erythrocytes is of great significance. A secondary outcome included revision of previously reported procedures for the handling of the whole blood sample. The purpose of this study was twofold. Firstly, the ultrastructural morphology of a healthy female's erythrocytes was examined via scanning electron microscopy (SEM) after exposure to the newly in silico-designed compounds. Morphology of erythrocytes following exposure to ESE-15-ol and ESE-16 for 3 minutes and 24 hours at 22°C were described with the use of SEM. The haemolytic activity of the compounds after 24 hours exposure were also determined with the ex vivo haemolysis assay. Secondly, storage conditions of the whole blood sample were investigated by determining morphological changes after a 24 hour storage period at 22°C and 37°C. RESULTS: No significant morphological changes were observed in the erythrocyte morphology after exposure to the novel anticancer compounds. Storage of the whole blood samples at 37°C for 24 hours resulted in visible morphological stress in the erythrocytes. Erythrocytes incubated at 22°C for 24 hours showed no structural deformity or distress. CONCLUSIONS: From this research the optimal temperature for ex vivo exposure of whole blood samples to ESE-15-ol and ESE-16 for 24 hours was determined to be 22°C. Data from this study revealed the potential of these compounds to be applied to ex vivo study techniques, since no damage occurred to erythrocytes ultrastructure under these conditions. As no structural changes were observed in erythrocytes exposed to ESE-15-ol and ESE-16, further ex vivo experiments will be conducted into the potential effects of these compounds on whole blood. Optimal incubation conditions up to 24 hours for whole blood were established as a secondary outcome.


Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Sulfonamidas/farmacología , Simulación por Computador , Inhibidores de Anhidrasa Carbónica/farmacología , Eritrocitos/efectos de los fármacos , Estradiol/análogos & derivados , Estrenos/farmacología , Antineoplásicos/farmacología , Sulfonamidas/toxicidad , Sulfonamidas/farmacocinética , Temperatura , Inhibidores de Anhidrasa Carbónica/farmacocinética , Disponibilidad Biológica , Microscopía Electrónica de Rastreo , Proteínas Portadoras/farmacología , Proteínas Portadoras/farmacocinética , Anhidrasa Carbónica II/efectos de los fármacos , Investigación Cualitativa , Eritrocitos/ultraestructura , Estradiol/toxicidad , Estradiol/farmacología , Estradiol/farmacocinética , Estrenos/farmacocinética , Descubrimiento de Drogas , Hemólisis/efectos de los fármacos , Antineoplásicos/farmacocinética
2.
Egyptian Journal of Histology [The]. 2013; 36 (4): 991-1002
en Inglés | IMEMR | ID: emr-160181

RESUMEN

Sildenafil citrate [SC] is an effective drug for treatment for erectile dysfunction, which is a common symptom in patients with liver disease. The effect of SC on liver structure is elusive and has not been thoroughly studied. The aim of this study was to investigate the effect of SC treatment for different periods and its withdrawal on the liver structure in adult male rats. Twenty-four adult male albino rats were classified into four groups: group I [control], group II [rats treated with SC orally at a dose of 10 mg/kg/day for 4 weeks], group III [rats treated with 10 mg/kg/day SC for 8 weeks] and group IV [recovery group; rats treated similarly as group III and then left for 4 weeks without SC treatment]. Liver specimens were processed for histological, histochemical and immunohistochemical study. In group II, the liver revealed significant enlargement of many hepatocytes with clumping of cell organelles in their cytoplasm. There were frequent Kupffer cells, activated hepatic stellate cells and increased deposition of collagen fibers. In group III, these changes were more marked, in addition to reduced glycogen staining in hepatocytes. Dilated bile ductules and cellular infiltration were noticed in many portal tract areas. In the recovery group, most changes were relatively reduced but not reversed completely. SC exerted deleterious structural effects on the hepatic tissue that were more pronounced with longer duration of SC administration. Some of these deleterious effects were reversible after discontinuation of the drug


Asunto(s)
Masculino , Animales de Laboratorio , Sulfonamidas/toxicidad , Hígado/ultraestructura , Inmunohistoquímica/estadística & datos numéricos , Ratas
3.
Indian J Exp Biol ; 2005 Jul; 43(7): 614-9
Artículo en Inglés | IMSEAR | ID: sea-58781

RESUMEN

Cyclooxygenase (COX-2) inhibitors were developed with the hope that they will cause fewer gastrointestinal adverse effects. Ability of selective as well as nonselective COX inhibitors to alter ischemia-reperfusion induced damage of gastric mucosa and hapten-induced colitis in rats has been compared. Celecoxib (10, 20 and 40 mg/kg(-l)) was significantly more potent at aggravating ischemia-reperfusion injury as compared to nimesulide. Similarly, celecoxib was found to maximally potentiate TNBS-induced colitis, followed by nimesulide and indomethacin. Celecoxib at its highest dose produced maximum deep histological injury. This paradoxic ulcer and colitis aggravating effect of selective COX-2 inhibitors may be explained by suppression of protective prostaglandins generated as a consequence of COX-2 induction in inflammatory states.


Asunto(s)
Animales , Colitis/etiología , Inhibidores de la Ciclooxigenasa/toxicidad , Mucosa Gástrica/irrigación sanguínea , Tracto Gastrointestinal/efectos de los fármacos , Indometacina/toxicidad , Masculino , Pirazoles/toxicidad , Ratas , Ratas Wistar , Daño por Reperfusión/etiología , Sulfonamidas/toxicidad
4.
Acta gastroenterol. latinoam ; 30(1): 27-33, mar. 2000. ilus, tab
Artículo en Español | LILACS | ID: lil-262234

RESUMEN

En diferentes grupos de ratas Wistar (n=15), se estudiaron AINEs inhibidores selectivos de la COX-2, como delecoxib y refecoxib, en cinco modelos experimentales: 1) Celecoxib y rofecoxib por vía oral y dosis dependiente durante 5 días y 24 hs. Después de indometacina oral. 2) Similar a 1, pero subcutáneo. 3) Ulcera gástrica inducida por ácido acético glacial. 4) Ulcera duodenal por cisteamina. 5) Estrés por inmovilización e inmersión en agua a 15 grados Celsius durante 6 horas. Celecoxib y rofecoxib por vía oral o SC en mucosa gastrointestinal sana no provaron lesiones necróticas en una superficie del 0 grados Celsius, presentanto histología normal; en cambio, agravaron y complicaron lesiones inducidas en forma previa por indometacina en más del 90 por ciento (p<0,001), con necrosis masiva del intestino delgado, así como ampliaron y causaron perforaciones en las úlceras gástricas y duodenales inducidas por ácido acético y cisteamina. Se produjo asimismo agravación de la zona necrótica gástrica por estrés en un 60-90 por ciento (p<0,05). Celecoxib y rofecoxib condujeron a una neutrofilia de 5000/mm3, similar a la inducida por la indometacina; en cambio, no produjeron infiltración leucocitaria en mucosa gástrica (MPO), siendo un marcador de AINE selectivo COX-2. Se concluyó que celecoxib y rofecoxib, administrados en dosis dependiente como inhibidores de COX-2 y no COX-1, no provocaron en mucosa gastrointestinal sana ninguna lesión por toxicidad, observándose un amplio margen terapéutico. En cambio, suministrados en mucosa gastrointestinal dañada agravaron y complicaron las lesiones ulcerosas gástricas y necróticas intestinales, limitando su uso en clínica.


Asunto(s)
Animales , Masculino , Femenino , Ratas , Inhibidores de la Ciclooxigenasa/toxicidad , Inhibidores Enzimáticos/toxicidad , Indometacina/toxicidad , Lactonas/toxicidad , Úlcera Péptica Perforada/inducido químicamente , Prostaglandina-Endoperóxido Sintasas , Úlcera Gástrica/inducido químicamente , Estrés Fisiológico , Sulfonamidas/toxicidad , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Indometacina , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Lactonas/administración & dosificación , Infiltración Neutrófila , Ratas Wistar , Sulfonamidas/administración & dosificación
5.
Medicina (B.Aires) ; 60(2): 221-4, 2000. ilus, tab
Artículo en Español | LILACS | ID: lil-262215

RESUMEN

En diferentes grupos de ratas Wistar (n = 15 en c/grupo), se estudiaron las dosis ulcerogénicas AINES COX-1 como Indometacina vs Celecoxib (inhibidor selectivo COX-2), en la producción de úlceras antrales gástricas y necrosis de la mucosa del intestino delgado y colon. Se encontró que Celecoxib, dado en forma oral o subcutánea cada 12 hs durante 5 días, no provocó lesiones en mucosa gastrointestinal, en cambio, dado el Celecoxib después de la Indometacina, agravé las úlceras antrales gástricas y dio necrosis masiva tanto del intestino delgado y del colon y óbito de todas las ratas. Se concluyó que Celecoxib no provocó lesiones gastrointestinales en mucosa sana; en contraste, se amplificaron las lesiones preexistentes gastrointestinales inducidas por Indometacina.


Asunto(s)
Animales , Ratas , Femenino , Antiinflamatorios no Esteroideos/efectos adversos , Inhibidores de la Ciclooxigenasa/toxicidad , Sistema Digestivo/efectos de los fármacos , Indometacina/efectos adversos , Úlcera Gástrica/inducido químicamente , Sulfonamidas/toxicidad , Inhibidores de la Ciclooxigenasa/administración & dosificación , Necrosis , Antro Pilórico/lesiones , Ratas Wistar , Úlcera Gástrica/patología , Sulfonamidas/administración & dosificación
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