Influence of cyclooxygenase inhibitors on the central histaminergic stimulations of hypothalamic - pituitary - adrenal axis.

Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of different neurotransmitters involved in activation of HPA axis. In the present experiment we investigated whether endogenous prostaglandins are involved in the stimulation of ACTH and corticosterone secretion by histaminergic systems in the rat brain. Histamine (50 microg), histamine-trifluoromethyl-toluidine derivative (HTMT, 75microg) a selective and potent H(1)-receptor agonist, and amthamine (50 microg) a H(2)-receptor agonist given intracerebroventricularly (i.c.v.) to non-anesthetized rats considerably increased ACTH and corticosterone secretion 1h after administration. A non-selective cyclooxygenase inhibitor indomethacin (2 mg/kg i.p. or 10 microg i.c.v.), piroxicam (0.02 and 0.2 microg i.c.v.) a more potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (0.1 and 1.0 microg i.c.v.), a selective inhibitor of inducible cyclooxygenase (COX-2) were given 15 min before histamine and histamine receptor agonists. One hour after the last injection trunk blood from decapitated rats was collected for hormones determination. The histamine-induced ACTH and corticosterone secretion was significantly diminished by piroxicam and was not markedly altered by indomethacin and compound NS-398. The HTMT-elicited increase in ACTH and corticosterone secretion was significantly prevented by indomethacin and was not affected by piroxicam or compound NS-398. The amthamine-evoked increase in ACTH and corticosterone secretion was not markedly influenced by any cyclooxygenase blocker applied in the present experiment. These results indicate that the histamine H(1)-receptor transmitted central stimulation of the HPA axis is considerably mediated by prostaglandins generated by consititutive cyclooxygenase, whereas stimulation transmitted via H(2)-receptor does not significantly depend on endogenous prostaglandins mediation.

DAINEs en el tratamiento del dolor postoperatorio / NSAIDs for the tratment of postoperative pain

En el presente trabajo se realizó una revisión de los artículos publicados en los últimos años sobre el tema, poniendo especial atención en la eficacia de estos agentes según el tipo de cirugía en que se emplean y la vía y el momento de administración más conveniente. Las DAINEs (drogas antiinflamatorias no esteroides) son los fármacos más utilizados en el mundo occidental. Son un grupo de drogas efectivas, y, en general, de bajo costo para el tratamiento del dolor postoperatorio. En los últimos años se produjo un gran avance en el conocimiento de su mecanismo de acción al descubrirse su acción central y la existencia de dos tipos de ciclooxigenasa: una constitutiva y otra inducida por la noxa, cuya inhibición es la que produce los efectos terapéuticos de las DAINEs. Esto permitió comprender más a fondo el mecanismo de producción de efectos adversos y permitirá el desarrollo de nuevas DAINEs con mayor especificidad tisular. Las DAINEs son efectivas como analgésicos únicos en cirugías de pequeña y mediana magnitud y como ahorradores de opioides en las de mayor envergadura. Las vías de elección para administrarlos son la endovenosa y la oral en cuanto es posible, comenzando antes del estímulo quirúrgico y continuando durante el postoperatorio para maximizar su eficacia y evitar el fenómeno de wind-up. Es de vital importancia identificar a los pacientes de riesgo para desarrollar efectos adversos, que pueden ser muy graves, y prevenir su aparición.

Modification of prostaglandin E2 and collagen synthesis in keratoconus fibroblasts, associated with an increase of interleukin 1 alpha receptor number.

Keratoconus, a bilateral corneal disease, is characterized by modifications in corneal shape and thinning of the stroma. It affects young people. From a biochemical point of view, a decrease in collagen content, probably due to the high collagenase activity, has been reported. In these experiments, we have studied the membrane receptors for interleukin 1 alpha, and the corresponding dissociation constant (KD). We also investigated synthesis of prostaglandin E2 (PGE2) and collagen, as well as kinetics of cyclooxygenase. Data from normal human corneas and from keratoconus were compared. Fibroblasts from keratoconus proved to bear four fold more IL1 binding sites than those from normal cornea, with similar KD. Both types of cells synthesize prostaglandin E2, even if IL1 is not added to the medium, but the keratoconus cells produce ten times more than the normal cornea cells. When the cells are stimulated with IL1, synthesis of PGE2 strongly increases and the amounts produced by keratoconus cells are always higher than those of the normal cornea cells. Kinetics of the cyclooxygenase show that Vmax. is 10 times higher in keratoconus than in normal cornea cells; Km's are the same. The amounts of collagen synthesized by keratoconus cells are slightly lower than those of normal cornea cells. Addition of IL1 to the cultures enhances synthesis of collagenase by the cells and decreases collagen found in the culture media. The drop of collagen is more important in keratoconus than in normal cornea cell cultures.