Increased apparent oral clearance of valproic acid during intake of combined contraceptive steroids in women with epilepsy.

Purpose: To determine potential changes in total and unbound serum valproic acid (VPA) concentrations at steady-state during a cycle of intake of combined hormonal contraceptive (HC) steroids.

Methods: Blood samples were collected from nine women stabilized on VPA monotherapy on two separate randomized occasions: (i) at the end of the 4- to 7-day HC-free interval, and (ii) on the last day of the HC intake period. Trough concentrations of VPA in serum and serum ultrafiltrates were determined by fluorescence polarization immunoassay.

Comparative analysis of the neuronal activation and cardiovascular effects of nitroglycerin, sodium nitroprusside and L-arginine.

In this study, we compare the biological effects, Fos expression and cardiovascular responses induced in the rat, of different nitric oxide modulators (nitroglycerin, sodium nitroprusside and L-arginine). Nitroglycerin and sodium nitroprusside induced a similar pattern of neuronal activation in several areas, which include the paraventricular and supraoptic nuclei of the hypothalamus, central nucleus of the amygdala, parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius. However, only nitroglycerin activated the periaqueductal grey and nucleus trigeminalis caudalis.

Central components of the analgesic/antihyperalgesic effect of nimesulide: studies in animal models of pain and hyperalgesia.

Unlabelled: The analgesic action of NSAIDs has been attributed to the peripheral inhibition of prostaglandin synthesis via the blockade of the enzyme cyclo-oxygenase (COX) and prevention of bradykinin and cytokine-induced hyperalgesia via inhibition of the release of tumour necrosis factor-alpha. However, it is becoming increasingly evident that NSAIDs exert their analgesic effect through several mechanisms. Recent data suggest that significant expression of COX-2 is found in the central nervous system, where COX-2 seems to have, together with nitric oxide, an important role in spinal nociceptive transmission.