Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

Synthesis of some new pyrazolo [4, 3-b] pyridine-3-one and dihydropyrazolo [4, 3-c] [1, 2] oxazine derivatives

Mixtures of malononitrile, aromatic aIdeyde, and 4-nitrosoantipyrine [5] were interacted in ethanolic piperidine solutions, in one-pot reaction to give the corresponding 6-aryl-1-methyl-3-oxo-2-phenyl-2, 3-dihydro-1H-pyrazolo [4, 3-b] pyridine-5 carbonitriles [3] or their corresponding 6-alkyl-4-hydroxy- 1-methyl-3-oxo-2-phenyl- 1, 2, 3, 4-tetrahydro-SH-pyrazolo [4,-3-b] pyridine-5, 5-dicarbonitrile [4] depending on reaction temperature. However, carrying out the above reaction using 3-methyl-4-oximmno-1-phenyl-1H-pyrazolin-5-one [15b] instead of compound [5], the corresponding 6-aryl-7a-hydroxy-3-methyl-1-phenyl- 1, 7a-dihydro-pyrazolo [4, 3-c] [1, 2] oxazine-7-carbonitrile [17] were obtained. Chalcones [9] were reacted also with compounds [5] and [15b], to afford the corresponding 5-aroyl-6-aryl-1-methel-2phenyl-1, 2-dihydro-3H-pyrazolo [4, 3-b] pyridine-3 ones [12], and aryl [6-aryl-3-methyl-1-phenyl-1, 4-dihydropyrazolo [4, 3-c] [1, 2] oxazin-5-yl] methan-ones [20]. Aniline hydrochloride was condensed with compounds [3] in acetic acid to give the corresponding N-phenyl-2, 3-dihydro-1 H-pyrazolo [4, 3-b] pyridine-5-carboximidamides 6, which were converted into the corresponding 1-phenyl-1 H-imidazole-4, 5-diones [7] by their reaction with oxaly 1 chloride. However, on reaction of ethylenediamine with compounds [3] in the presence of p-toluenesulfonic acid, the corresponding 6-aryl-5-[4, 5-dihydro-1 H-imidazol-2-y1]-1-methyl-2-phenyl-1, 2-dihydropyrazolo [4, 3-b] pyridin-3-ones [8] were obtained

Tratamieno de la cefalea de origen diverso con la combinación analgesica dihidroergotamina, butalbital, propitenazona y cafeína: estudio doble ciego contra placebo / Treatment of headaches of differnt origins with the analgesic combination dihydroergotamine, butalbital, propyphenazone and caffein: double-blind study against placebo

En un estudio doble ciego comparativo contra placebo, se incluyó a 37 pacientes con cefalea de origen diverso; 17 de ellos recibieron una combinación analgésica de mesilato de dehidroergotamina (0.5 mg), butalbital (45 mg), propifenazona (125 mg) y cafeína (40 mg) en dosis de dos grageas cada seis horas, hasta un máximo de seus grageas por día, quedando 20 pacientes que recibieron placebo, en presentación idéntica al medicamento estudiado. El origen de la cefalea fue diverso tanto en el grupo que recibió el principio activo como en el grupo placebo; la localización y evolución de las cefaleas fueron similares en ambos grupos. Mediante el tratamiento, que tuvo una duración de cinco días, la intensidad del dolor de acuerdo a una escala de valoración previamente establecida, descendió de 3.23 ñ 0.90 a 0.82 ñ 1.28 en el grupo tratado, mientras que en el grupo placebo el descenso no fue estadísticamente significativo. Se analizó también el número de grageas requeridas, tiempo de instalación del efecto terapéutico y su duración, así como los efectos indeseables que se presentaron en cada grupo. Se concluye que la combinación analgésica demostró ser útil en el tratamiento de la cefalea de diverso origen

Dihidroergotamina, propifenazona y cafeína: combinación analgésica para tratamiento de cefalea de origen diverso / Dihydroergotamine, propyphenazone and caffeine: analgesic combination for treatment of headache of different origin

Se estudiaron 20 pacientes de ambos sexos con cefalea de origen diverso a quienes se administró la combinación analgésica dihidroergotamina, propifenazona y cafeína en una solo gragea, en dosis de dos grageas iniciales y cada seis horas hasta alcanzar el efecto terapéutico o la dosis máxima de seis grageas. La edad promedio de los pacientes fue de 31.7 ñ 11.6 años. Se observaron efectos indeseables graves en dos casos; sin embargo no fue necesario suspender el tratamiento en ninguno. Finalmente la combinación analgésica estudiada demostró ser eficaz en el tratamiento de cefalea de origen diverso y fue bien tolerada en dosis terapéuticas