Efectos del danazol y hemisuccinato de danazol sobre la presión de perfusión y resistencia vascular / Effects of danazol and danazol hemisuccinate on perfusión pressure and vascular resistance

Estudios clínicos y epidemiológicos sugieren que el danazol ha sido considerado como un factor de riesgo para desarrollar hipertensión. Para proporcionar información adicional acerca de este fenómeno, en este trabajo fue caracterizado el efecto inducido por el danazol y el hemisuccinato de danazol sobre la presión de perfusión y la resistencia vascular en corazón aislado de rata a flujo constante (modelo de Langendorff). Los resultados, mostraron que; 1) el hemisuccinato de danazol [10-9 M] incrementa la presión de perfusión en comparación con el danazol [10-9 M]; 2) los efectos del derivado de danazol [10-9 M - 10-4 M] sobre la presión de perfusión fueron inhibidos por flutamida [10-6 M]; 3) la nifedipina [10-6 M], bloqueó los efectos ejercidos por el hemisuccinato de danazol [10-9 M -10-4 M] sobre la presión de perfusión y 4) el efecto del derivado de danazol [10-9 M - 10-4 M] sobre la presión de perfusión en presencia del montelukast [10-6 M] fue inhibido significativamente (p=0,008). En conclusión, los efectos inducidos por el danazol y hemisuccinato de danazol sobre la presión de perfusión y la resistencia vascular podrían depender de su estructura química. Este fenómeno podría involucrar la interacción del receptor de andrógenos e indirectamente la activación de la síntesis de leucotrienos D4 (LTD4) y consecuentemente inducir variaciones en la presión de perfusión.

Epidemiological and clinical studies suggest that danazol has been considered a risk factor for hypertension development. In order to provide additional information about this phenomenon, the effect induced by both danazol and hemisuccinate of danazol on perfusion pressure and vascular resistance was characterized in isolated rat heart at constant flow (Langendorff model) and it was evaluated in this work.The results showed that; 1) hemisuccinate of danazol [10-9 M] increases perfusion pressure and vascular resistance in comparison with danazol [10-9 M]; 2) the effects of danazol-derivative [10-9 M - 10-4 M] on perfusion pressure were inhibited by flutamide [10-6 M]; 3) nifedipine [10-6 M] blockaded the effects exerted by hemisuccinate of danazol [10-9 M -10-4 M] on perfusion pressure; and 4) the effect of danazol-derivative [10-9 M - 10-4 M] on perfusion pressure in presence of montelukast [10-6 M] was significantly inhibited (p=0.008). In conclusion, the effects induced by both danazol and hemisuccinate of danazol on perfusion pressure and vascular resistance could depend on their chemical structure. This phenomenon could involve the interaction of androgene steroid-receptor and indirect activation of leukotriene D4 (LTD4) synthesis and consequently, induce variations in the perfusion pressure.

Comparison of methylprednisolone with dexamethasone in treatment of acute spinal injury in rats.

Effect of methylprednisolone sodium succinate (MPSS) and its comparison with dexamethasone in experimentally induced acute spinal cord compression in adult rats was studied. The rats were divided into group A (control) and group B, which was subdivided into B1, B2, B3 where MPSS was given after 1, 8 and 24 hr and B4 where dexamethasone was given after 1 hr of cord injury respectively. Proper neurological evaluation was done with mobility, running and climbing score. Recovery index was evaluated for 7 days. After sacrificing the rats, spinal cord was observed histopathologically. Mean recovery index and microscopic findings based on hemorrhage in gray and white matter, neuronal degeneration, hematomyelia and edema in white matter were recorded. The results suggested that MPSS was effective in promoting post-traumatic clinical and histological recovery and to a greater extent, when given 1 hr after trauma. MPSS is more effective than dexamethasone in reducing edema when both are given after interval of 1 hr.

Effects of Corticosteroid and Electroacupuncture on Experimental Spinal Cord Injury in Dogs

The aim of this study is to investigate the effects of electroacupuncture, corticosteroid, and combination of two treatments on ambulatory paresis due to spinal cord injury in dogs by comparing therapeutic effects of electroacupuncture and corticosteroid. Spinal cord injury was induced in twenty healthy dogs (2.5~7 kg and 2~4 years) by foreign body insertion which compressed about 25% of spinal cord. There was no conscious proprioception, no extensor postural thrust, and ambulatory. Dogs were divided into four groups according to the treatment; corticosteroid (group A), electroacupuncture (group B), corticosteroid and electroacupuncture (group AB), and control (group C). Neurological examination was performed everyday to evaluate the spinal cord dysfunction until motor functions were returned to normal. Somatosensory evoked potentials (SEPs) were measured for objective and accurate evaluations. The latency in measured potentials was converted into the velocity for the evaluation of spinal cord dysfunctions. Pain perceptions were normal from pre-operation to 5 weeks after operation. Recovery days of conscious proprioception in groups A, B, AB, and C were 21.2+/-8.5 days, 19.8+/-4.3 days, 8.2+/-2.6 days, and 46.6+/-3.7 days, respectively. Recovery days of extensor postural thrust in group A, group B, group AB, and group C were 12.8+/-6.8 days, 13.8+/-4.8 days, 5.4+/-1.8 days, and 38.2+/-4.2 days, respectively. There were no significant differences between group A and group B. However, recovery days of group AB was significantly shorter than that of other groups and that of group C was significantly delayed (p<0.05). Conduction velocities of each group were significantly decreased after induction of spinal cord injury on SEPs (p<0.05) and they showed a tendency to return to normal when motor functions were recovered. According to these results, it was considered that the combination of corticosteroid and electroacupuncture was the most therapeutically effective for ambulatory paresis due to spinal cord injury in dogs.