Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex

ABSTRACT Objective: To evaluate the effect of neuronal nitric oxide synthase on the striated urethral sphincter and the urinary bladder. Materials and Methods: A coaxial catheter was implanted in the proximal urethra and another one in the bladder of female rats, which were anesthetized with subcutaneous injection of urethane. The urethral pressure with saline continuous infusion and bladder isovolumetric pressure were simultaneously recorded. Two groups of rats were formed. In group I, an intrathecal catheter was implanted on the day of the experiment at the L6-S1 level of the spinal cord; in group II, an intracerebroventricular cannula was placed 5-6 days before the experiment. Results: It was verified that the group treated with S-methyl-L-thio-citrulline, via intrathecal pathway, showed complete or partial inhibition of the urethral sphincter relaxation and total inhibition of the micturition reflexes. The urethral sphincter and the detrusor functions were recovered after L-Arginine administration. When S-methyl-L-thio-citrulline was administered via intracerebroventricular injection, there was a significant increase of urethral sphincter tonus while preserving the sphincter relaxation and the detrusor contractions, at similar levels as before the use of the drugs. Nevertheless there was normalization of the urethral tonus when L-Arginine was applied. Conclusions: The results indicate that, in female rats anaesthetized with urethane, the nNOS inhibitor administrated through the intrathecal route inhibits urethral sphincter relaxation, while intracerebroventricular injection increases the sphincter tonus, without changing bladder function. These changes were reverted by L-Arginine administration. These findings suggest that the urethral sphincter and detrusor muscle function is modulated by nitric oxide.

El intercambiador Na+/Ca2+ como responsable del atontamiento miocardio / The Na+/Ca2+ exchanger as responsible of myocardial stunning

Nuestro objetivo fue examinar la participación de los intercambiadores Na+/H+ (NHE) y Na+/Ca+2 (NCX) sobre las alteraciones sistólicas propias del atontamiento miocárdio. Se utilizó el modelo de corazón aislado isovolúmico de rata el cual fue sometido a 20 minutos de isquemia global (Is) y 30 minutos de perfusión (R). Este protocolo se repitió en prasencia de 1microM de HOE 642, bloqueante específico del NHE-1 y de KB-R7943, bloqueante del modo inverso del NCX (entrando Ca+2 y sacando Na de la célula) administrados antes de la Is, y/o en la R. En los controles isquémicos la contractilidad, evaluada a través de la +dP/dtmax se recuperó aproximadamente un 60 porciento. La recuperación postisquémica fue total cuando el bloqueo de NHE fue efectuado antes de la Is o al comienzo de la R y mejoró significativamente cuando en Is y R bloqueó el NCX ( 95 + o - 7 porciento). La contractura isquémica disminuyó com ambos tratamientos cuando fueron realizados previos a la Is. El aumento de la PDF observado en la R (24 + o - 6 y 12 + o - 2 mmHg) y por el bloqueo del NCX realizado durante Is y R (12 + o - 6 mmHg). Estos resultados indican que la activación del modo inverso del NCX secundaria a una activación del NHE (que incrementa el Na+ intracelular) durante la isquemia y reperfusión es el mecanismo culpable de la sobrecarga de Ca+2 involucrado en la disminuición de la contractilidad que caracteriza al miocardio atontado.

Mutagenic and genotoxic effects of mate (Ilex paraguariensis) in prokaryotic organisms

1. The mutagenic and genotoxic effects of mate (Ilex paraguariensis) aqueous solutions were analyzed in bacterial cells. 2. Mate solutions showed mutagenic activity in the Ames test (TA97, TA98, TA100 and TA102 strains) at concentrations of 20 to 50 mg/plate (mutagenic factors of 3.5 to 5.6) and genotoxic activity in the inductest (WP2s (lambda) strain), with a maximal phage induction at concentrations of 10 to 20 mg/plate. Above these concentrations the mate solutions were cytotoxic. 3. Addition of 5 U/ml catalase, 20 microliters/ml S9 rat liver microsomal fraction, 100 mM thiourea or 10 mM dipyridyl completely inhibited the lysogenic induction produced by mate; however, the addition of 1,000 U/ml superoxide dismutase was almost ineffective. 4. Oxygen reactive species may be present in mate solutions playing an essential role in its genotoxicity.

Antagonizing the hydroxyl ion free radical (HO.) does not abolish reperfusion ventricular fibrillation in anesthetized dogs

1. The hypothesis that the hydroxyl ion free radical, HO; derived from O2 plays a pivotal role in the development of reperfusion ventricular fibrillation was tested in 63 anesthetized mongrel dogs of either sex weighing 14 +/- 7 kg submitted to 90-min coronary occlusion followed by 60-min reperfusion. 2. OH. was blocked by the iron chelator deferoxamine (DF, 500 mg) and by dimethylthiourea (DMTU, 500 mg/kg), a HO. scavenger both given iv over 30 min before reperfusion. 3. The frequency of reperfusion ventricular fibrillation was similar in all animals, i.e., 7/27 (26 per cent ) control dogs, 7/23 (30 per cent ) DF-treated dogs and 3/13 (23 per cent ) DMTU-treated dogs. Arterial pressure, heart rate and double product were not significantly different among the three groups during occlusion or reperfusion. The hemodynamic variables were also similar among dogs that fibrillated and those that did not. Likewise, extent of ischemic areas and necrosis was similar among the three experimental groups, with the control values being 34 +/- 4 per cent and 14 +/- 5 per cent , respectively. 4. We conclude that OH. does not play a major role in the induction of reperfusion ventricular fibrillation in the anesthetized dog with ischemia/necrosis

Estabilidad del sulfato de salbutamol inyectable: parte III / Stability of injectable salbutamol sulfate: part III

Se describen los resultados obtenidos en el estudio cinético del sulfato de salbutamol inyectable empleando como antioxidante la tiourea. Se destaca la importancia del tipo de envase empleado en cuanto al incremento de la estabilidad del producto de acuerdo con la predicción de vida útil obtenida para la formulación inyectable

Estudo quantitativo e morfométrico das vesículas "pinocíticas" dos capilares pulmonares do rato em situaçäo normal e de edema agudo / Quantitative and morphometric study of lung capillary \"pinocytic\" vesicles of rats in normal condition and in acute edema

Vesículas "pinocíticas" do endotélio capilar alveolar do pulmäo de rato foram estudadas quantitativamente e por técnicas morfométricas. Em casos de edema pulmonar induzido pela alfa-naftil-tiouréia, näo se observou aumento numérico mas, apenas, volumétrico das vesículas em relaçäo a animais controles. Esta alteraçäo de volume pode traduzir aumento de transporte de fluido e também constituir a fase inicial de processo degenerativo que leva a vacúolos e bolhas citoplasmáticas, comumente encontrados nos edemas pulmonares. Nos pulmöes normais, bem como naqueles com edema, verificaram-se quatro padröes populacionais de vesículas, que fortalecem a hipótese de que estas estruturas näo constituem um único tipo de organela, mas, sim, vários e com funçöes distintas. Recomenda-se substituir o termo "vesículas pinocíticas" por "vesículas citoplasmáticas", a fim de evitar a limitaçäo funcional sugerida por aquela denominaçäo

Estabilidad del sulfato de salbutamol: nebulizaciones (parte II) / Stability of salbutamol sulfate: nebulizations (part II)

Se describe el efecto producido por la tiourea cuando es utilizada como antioxidante en la estabilización del sulfato de salbutamol y se compara con el metabisulfito de sodio empleado con el mismo propósito. Se informan parámetros cinéticos tales como: orden de la reacción, factor de frecuencia y energía de activación obtenidos en la descomposición oxidativa del principio activo. Se emplean cálculos estadísticos para el tratamiento matemático de los datos. Se aplica como método analítico, un método colorimétrico complementando con cromatografía en capa delgada. Se estudia la influencia del envase en la estabilidad del producto terminado

Tratamento clinico da doenca de Graves. / Clinical treatment of Graves' disease

Os autores reveem e discutem as diferentes substancias utilizadas no tratamento clinico da doenca de Graves. Apresentam ainda a experiencia do Servico de Endocrinologia do Hospital do Servidor Publico Estadual "Francisco Morato de Oliveira" no tratamento desta doenca com as drogas antitiroidianas